This article is about the general scientific term. For the scientific journal, see Genetics (journal).
For a generally accessible and less technical introduction to the topic, see Introduction to genetics.
DNA, the molecular basis for inheritance. Each strand of DNA is a chain of nucleotides, matching each other in the center to form what look like rungs on a twisted ladder.Genetics, a discipline of biology, is the science of heredity and variation in living organisms.[1][2] Knowledge of the inheritance of characteristics has been implicitly used since prehistoric times for improving crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the mechanisms of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century.[3] Although he did not know the physical basis for heredity, Mendel observed that inheritance is fundamentally a discrete process where specific traits are inherited in an independent manner—these basic units of inheritance are now called genes.
Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for synthesis of a new partner strand—this is the physical mechanism for the copying and inheritance of genetic information.
The sequence of nucleotides in DNA is used by cells to produce specific sequences of amino acids, creating proteins—a correspondence known as the genetic code. This sequence of amino acids in a protein determines how it folds into a three-dimensional structure, this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live and reproduce. A change to DNA sequence can change a protein's structure and behavior, and this can have dramatic consequences in the cell and on the organism as a whole.
Although genetics plays a large role in determining the appearance and behavior of organisms, it is the interaction of genetics with the environment an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining a person's height, the nutrition and health that person experiences in childhood also have a large effect.
History
Morgan's observation of sex-linked inheritance of a mutation causing white eyes in Drosophila led him to the hypothesis that genes are located upon chromosomes.Although the science of genetics has its origins in the work of Gregor Mendel in the mid-nineteenth century, various theories of inheritance preceded Mendel. These theories generally assumed that there existed an inheritance of acquired characteristics: the belief that individuals inherit traits that have been strengthened in their parents. Today, the theory is commonly associated with Jean-Baptiste Lamarck, who used this pattern of inheritance to explain the evolution of various traits within species (these changes are now understood to be the product of natural selection rather than a product of soft inheritance).[4]
Mendelian and classical genetics
The modern science of genetics traces its roots to the observations made by Gregor Johann Mendel, a German-Czech Augustinian monk and scientist who made detailed studies of the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Brunn Natural History Society, Gregor Mendel traced the inheritance patterns of certain traits in pea plants and showed that they could be described mathematically.[5] Although not all features show these patterns of Mendelian inheritance, his work suggested the utility of the application of statistics to the study of inheritance.
The significance of Mendel's observations was not understood until early in the twentieth century, after his death, when his research was re-discovered by other scientists working on similar problems. The word genetics itself was coined in 1905 by William Bateson, a significant proponent of Mendel's work, in a letter to Adam Sedgwick.[6][7] (The adjective genetic, derived from the Greek word genno (γεννώ): to give birth, predates the noun and was first used in a biological sense in 1860.[8]) Bateson publicly promoted and popularized usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London, England, in 1906.[9]
In the decades following rediscovery and popularization of Mendel's work, numerous experiments sought to elucidate the molecular basis of DNA. In 1910 Thomas Hunt Morgan argued that genes reside on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.[10] In 1913 his student Alfred Sturtevant used the phenomenon of genetic linkage and the associated recombination rates to demonstrate and map the linear arrangement of genes upon the chromosome.[11]
James D. Watson (pictured) and Francis Crick resolved the structure of DNA in 1953.
Molecular genetics
Although chromosomes were known to contain genes and composed of both protein and DNA, it was unknown which was critical for heredity or how the process occurred. In 1928, Frederick Griffith published his discovery of the phenomenon of transformation (see Griffith's experiment); sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty used this phenomenon to isolate and identify the molecule responsible for transformation as DNA.[12] The Hershey-Chase experiment in 1952 identified DNA (rather than protein) as the genetic material of the viruses that infect bacteria, further evidence that DNA was the molecule responsible for inheritance.[13]
James D. Watson and Francis Crick solved the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin that indicated the molecule had a helical structure.[14][15] Their double-helix model paired a sequence of nucleotides with complementary nucleotides on the other strand.[16] This structure not only provided a physical explanation for how information is contained within the order of the nucleotides, but also suggested a simple mechanism for duplication—through separation of strands and the reconstruction of partner strands based on the nucleotide sequences. Although the structure explained the process of inheritance, it was still unknown how DNA influenced the behavior of cells. In the following years scientists sought to understand how DNA controls the process of protein production within ribosomes, eventually discovering the transcription of DNA into messenger RNA and cracking the genetic code, which links the nucleotide sequence of messenger RNA to the amino acid sequence of protein.
With this molecular understanding of inheritance, an explosion of research that applied this new knowledge to biology became possible. One early development was chain-termination DNA sequencing in 1977, which enabled the determination of nucleotide sequences on DNA.[17] In 1983 the polymerase chain reaction, developed by Kary Banks Mullis, provided a simple method for isolating and amplifying segments of DNA.[18] These and other techniques, through the pooled efforts of the Human Genome Project and parallel private effort by Celera Genomics, culminated in the sequencing of the human genome in 2003.[19]
Features of inheritance
A Punnett square depicting a cross between two pea plants heterozygous for purple (B) and white (b) blossomsAt its most fundamental level, inheritance in organisms occurs by means of discrete traits, called genes.[20] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.[5][21] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white—and never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles.
In the case of pea plants, each organism has two alleles of each gene, and the plants inherit one allele from each parent.[22] Many organisms, including humans, have this pattern of inheritance. Organisms with two copies of the same allele are called homozygous, while organisms with two different alleles are heterozygous.
The set of alleles for a given organism is called its genotype, while the observable trait the organism has is called its phenotype. When organisms are heterozygous, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.[23]
When a pair of organisms reproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known as Mendel's first law or the Law of Segregation.
Genetic pedigree charts help track the inheritance patterns of traits.
[edit] Notation and diagrams
Geneticists use diagrams and symbols to describe inheritance. A gene is represented by a letter (or letters)—the capitalized letter represents the dominant allele and the recessive is represented by lowercase.[24] Often a "+" symbol is used to mark the usual, non-mutant allele for a gene.
In fertilization and breeding experiments (and especially when discussing Mendel's) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is the Punnett square.
When studying human genetic diseases, geneticists often use pedigree charts to represent the inheritance of traits.[25] These charts map the inheritance of a trait in a family tree.
[edit] Interactions of multiple genes
Human height is a complex genetic trait. Francis Galton's data from 1889 shows the relationship between offspring height as a function of mean parent height. While correlated, remaining variation in offspring heights indicates environment is also an important factor in this trait.Organisms have thousands of genes, and in sexually reproducing organisms assortment of these genes are generally independent of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law" or the "Law of independent assortment", means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)
Often different genes can interact in a way that influences the same trait. In the Blue-eyed Mary, for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all: color or white. When a plant has two copies of this white allele, its flowers are white—regardless of whether the first gene has blue or magenta alleles. This interaction between genes is called epistasis, with the second gene epistatic to the first.[26]
Many traits are not discrete features (eg. purple or white flowers) but are instead continuous features (eg. human height and skin color). These complex traits are the product of interactions of many genes.[27] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is called heritability.[28] Measurement of the heritability of a trait is relative, although—in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a complex trait with a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.[29]
Molecular basis for inheritance
DNA and chromosomes
The molecular structure of DNA. Bases pair through the arrangement of hydrogen bonding between the strands.The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[30] Viruses are the only exception to this rule—sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material.[31]
DNA normally exists as a double-stranded molecule, coiled into the shape of a double-helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.[32]
Genes are arranged linearly along long chains of DNA sequence, called chromosomes. In bacteria, each cell has a single circular chromosome, while eukaryotic organisms (which includes plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.[33] The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes chromatin is usually composed of nucleosomes, repeating units of DNA wound around a core of histone proteins.[34] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome.
While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene.[35] The two alleles for a gene are located on identical loci of sister chromatids, each allele inherited from a different parent.
Walther Flemming's 1882 diagram of eukaryotic cell division. Chromosomes are copied, condensed, and organized. Then, as the cell divides, chromosome copies separate into the daughter cells.An exception exists in the sex chromosomes, specialized chromosomes many animals have evolved that play a role in determining the sex of an organism.[36] In humans and other mammals the Y chromosome has very few genes and triggers the development of male sexual characteristics, while the X chromosome is similar to the other chromosomes and contains many genes unrelated to sex determination. Females have two copies of the X chromosome, but males have one Y and only one X chromosome—this difference in X chromosome copy numbers leads to the unusual inheritance patterns of sex linked disorders.
Reproduction
Main articles: Asexual reproduction and Sexual reproduction
When cells divide, their full genome is copied and each daughter cell inherits one copy. This process, called mitosis, is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that are genetically identical to their parents are called clones.
Eukaryotic organisms often use sexual reproduction to generate offspring that contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction generally alternates between forms that contain single copies of the genome (haploid) and double copies (diploid).[35] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell gametes.
Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.[37] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genome, a phenomenon known as transformation.[38] This processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would otherwise be unrelated.
Recombination and linkage
Main articles: Chromosomal crossover and Genetic linkage
The diploid nature of chromosomes allows for genes on different chromosomes to assort independently during sexual reproduction, recombining to form new combinations of genes. Genes on the same chromosome would theoretically never recombine, however, were it not for the process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[39] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid germ cells that later combine with other germ cells to form child organisms.
The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between them. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated. For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage—alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear linkage map that roughly describes the arrangement of the genes along the chromosome.[40]
Gene expression
The genetic code: DNA, through a messenger RNA intermediate, codes for protein with a triplet code.
[edit] Genetic code
Main article: Genetic code
Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell.[41] Proteins are chains of amino acids, and the DNA sequence of a gene (through an RNA intermediate) is used to produce a specific protein sequence. Each group of three nucleotides in the sequence, called a codon, corresponds to one of the twenty possible amino acids in protein—this correspondence is called the genetic code.[42] The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but never from protein back into the sequence of DNA—a phenomenon Francis Crick called the central dogma of molecular biology.[43]
The dynamic structure of hemoglobin is responsible for its ability to transport oxygen within mammalian blood.
A single amino acid change causes hemoglobin to form fibers.The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of protein are related to their function.[44][45] Some are simple structural molecules, like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as enzymes by facilitating chemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein hemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.
A single nucleotide difference within DNA can cause a single change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, sickle-cell anemia is a human genetic disease that results from a single base difference within the coding region for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.[46] Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with the disease.
Nature vs. nurture
Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotype—a dichotomy often referred to as "nature vs. nurture". The phenotype of an organism depends on the interaction of genetics with the environment. One example of this is the case of temperature-sensitive mutations. Often, a single amino acid change within the sequence of a protein does not change its behavior and interactions with other molecules, but it does destabilize the structure. In a high temperature environment, where molecules are moving more quickly and hitting each other, this results in the protein losing its structure and failing to function. In a low temperature environment, however, the protein's structure is stable and functions normally. This type of mutation is visible in the coat coloration of Siamese cats, where a mutation in an enzyme responsible for pigment production causes it to destabilize and lose function at high temperatures.[47] The protein remains functional in areas of skin that are colder—legs, ears, tail, and face—and so the cat has dark fur at its extremities.
Siamese cats have a temperature-sensitive mutation in pigment production.Environment also plays a dramatic role in effects of the human genetic disease phenylketonuria.[48] The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive mental retardation and seizures. If someone with the phenylketonuria mutation is kept on a strict diet that avoids this amino acid, however, they remain normal and healthy.
Gene regulation
Main article: Regulation of gene expression
The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA (and translated into protein), and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. Transcription factors are regulatory proteins that bind to the start of genes, either promoting or inhibiting the transcription of the gene.[49] Within the genome of Escherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid tryptophan. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genes—tryptophan molecules bind to the tryptophan repressor (a transcription factor), changing the repressor's structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating negative feedback regulation of the tryptophan synthesis process.[50]
Transcription factors bind to DNA, influencing the transcription of associated genes.Differences in gene expression are especially clear within multicellular organisms, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into different cell types in response to external and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. No single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.
Within eukaryotes there exist structural features of chromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.[51] These features are called "epigenetic" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types grown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of paramutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.[52]
Genetic change
Gene duplication allows diversification by providing redundancy: one gene can mutate and lose its original function without harming the organism.
Mutations
Main article: Mutation
During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can have an impact on the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.[53][54] (Without proofreading error rates are a thousand-fold higher; because many viruses rely on DNA and RNA polymerases that lack proofreading ability they experience higher mutation rates.) Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure.[55] Chemical damage to DNA occurs naturally as well, and cells use DNA repair mechanisms to repair mismatches and breaks in DNA—nevertheless, the repair sometimes fails to return the DNA to its original sequence.
In organisms that use chromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations.[56] Errors in crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequence—duplications, inversions or deletions of entire regions, or the accidental exchanging of whole parts between different chromosomes (called translocation).
Natural selection and evolution
Main article: Evolution
Mutations produce organisms with different genotypes, and those differences can result in different phenotypes. Many genetic mutations have a negligible effect on an organism's phenotype, health, and reproductive fitness. Mutations that do have an effect are often deleterious, but occasionally mutations arise that are beneficial in the current environmental context of the organism.
An evolutionary tree of eukaryotic organisms, constructed by comparison of several orthologous gene sequencesPopulation genetics research studies the distributions of these genetic differences within populations and how the distributions change over time.[57] Changes in the frequency of an allele in a population can be influenced by natural selection, where a given allele's higher rate of survival and reproduction causes it to become more frequent in the population over time.[58] Genetic drift can also occur, where chance events lead to random changes in allele frequency.[59]
Over many generations, the genomes of organisms can change, resulting in the phenomenon of evolution. Mutations and the selection for beneficial mutations can cause a species to evolve into forms that better survive their environment, a process called adaptation.[60] New species are formed through the process of speciation, a process often caused by geographical separations that allow different populations to genetically diverge.[61]
As sequences diverge and change during the process of evolution, these differences between sequences can be used as a molecular clock to calculate the evolutionary distance between them.[62] Genetic comparisons are generally considered the most accurate method of characterizing the relatedness between species, an improvement over the sometimes deceptive comparison of phenotypic characteristics. The evolutionary distances between species can be combined to form evolutionary trees—these trees represent the common descent and divergence of species over time, although they cannot represent the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).
Research and technology
The common fruit fly (Drosophila melanogaster) is a popular model organism in genetics research.
Model organisms and genetics
Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research.[63] Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer.
Organisms were chosen, in part, for convenience—short generation times and facile genetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), and the common house mouse (Mus musculus).
Medical genetics research
Medical genetics seeks to understand how genetic variation relates to human health and disease.[64] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a technique especially useful for multigenic traits not clearly defined by a single gene.[65] Once a candidate gene is found, further research is often done on the same gene (called an orthologous gene) in model organisms. In addition to studying genetic diseases, the increased availability of genotyping techniques has led to the field of pharmacogenetics—studying how genotype can affect drug responses.[66]
Although it is not an inherited disease, cancer is also considered a genetic disease.[67] The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide—while these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process—signals are given to inappropriately dividing cells that should trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body.
E coli colonies on a plate of agar, an example of cellular cloning and often used in molecular cloning
Research techniques
DNA can be manipulated in the laboratory. Restriction enzymes are a commonly used enzyme that cuts DNA at specific sequences, producing predictable fragments of DNA.[68] The use of ligation enzymes allows these fragments to be reconnected, and by ligating fragments of DNA together from different sources, researchers can create recombinant DNA. Often associated with genetically modified organisms, recombinant DNA is commonly used in the context of plasmids—short circular DNA fragments with a few genes on them. By inserting plasmids into bacteria and growing those bacteria on plates of agar (to isolate clones of bacteria cells), researchers can clonally amplify the inserted fragment of DNA (a process known as molecular cloning). (Cloning can also refer to the creation of clonal organisms, through various techniques.)
DNA can also be amplified using a procedure called the polymerase chain reaction (PCR).[69] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences.
DNA sequencing and genomics
One of the most fundamental technologies developed to study genetics, DNA sequencing allows researchers to determine the sequence of nucleotides in DNA fragments. Developed in 1977 by Frederick Sanger and coworkers, chain-termination sequencing is now routinely used to sequence DNA fragments.[70] With this technology, researchers have been able to study the molecular sequences associated with many human diseases. As sequencing has become less expensive and with the aid of computational tools, researchers have sequenced the genomes of many organisms by stitching together the sequences of many different fragments (a process called genome assembly).[71] These technologies were used to sequence the human genome, leading to the completion of the Human Genome Project in 2003.[19]
The large amount of sequences available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data.
From Wikipedia, the free encyclopedia
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Biomechanics
This article may require cleanup to meet Wikipedia's quality standards.Please improve this article if you can. (March 2008)
Biomechanics is mechanics applied to biology (Fung). This includes research and analysis of the mechanics of living organisms and the application of engineering principles to and from biological systems. This research and analysis can be carried forth on multiple levels, from the molecular, wherein biomaterials such as collagen and elastin are considered, all the way up to the tissue and organ level. Some simple applications of Newtonian mechanics can supply correct approximations on each level, but precise details demand the use of continuum mechanics.
Chinstrap Penguin
Giovanni Alfonso Borelli wrote the first book on biomechanics, De Motu Animalium, or On the Movement of Animals. He not only saw animals' bodies as mechanical systems, but pursued questions such as the physiological difference between imagining performing an action and actually doing it. Some simple examples of biomechanics research include the investigation of the forces that act on limbs, the aerodynamics of bird and insect flight, the hydrodynamics of swimming in fish, the anchorage and mechanical support provided by tree roots, and locomotion in general across all forms of life, from individual cells to whole organisms. The biomechanics of human beings is a core part of kinesiology.
Applied mechanics, most notably thermodynamics and continuum mechanics, and mechanical engineering disciplines such as fluid mechanics and solid mechanics, play prominent roles in the study of biomechanics. By applying the laws and concepts of physics, biomechanical mechanisms and structures can be simulated and studied.
It has been shown that applied loads and deformations can affect the properties of living tissue. There is much research in the field of growth and remodeling as a response to applied loads. For example, the effects of elevated blood pressure on the mechanics of the arterial wall, the behavior of cardiomyocytes within a heart with a cardiac infarct, and bone growth in response to exercise, and the acclimative growth of plants in response to wind movement, have been widely regarded as instances in which living tissue is remodelled as a direct consequence of applied loads.
Relevant mathematical tools include linear algebra, differential equations, vector and tensor calculus, numerics and computational techniques such as the finite element method.
The study of biomaterials is of crucial importance to biomechanics. For example, the various tissues within the body, such as skin, bone, and arteries each possess unique material properties. The passive mechanical response of a particular tissue can be attributed to characteristics of the various proteins, such as elastin and collagen, living cells, ground substances such as proteoglycans, and the orientations of fibers within the tissue. For example, if human skin were largely composed of a protein other than collagen, many of its mechanical properties, such as its elastic modulus, would be different.
Chemistry, molecular biology, and cell biology have much to offer in the way of explaining the active and passive properties of living tissues. For example, in muscle contractions, the binding of myosin to actin is based on a biochemical reaction involving calcium ions and ATP.
Applications
The study of biomechanics ranges from the inner workings of a cell to the movement and development of limbs, to the mechanical properties of soft tissue, and bones. As we develop a greater understanding of the physiological behavior of living tissues, researchers are able to advance the field of tissue engineering, as well as develop improved treatments for a wide array of pathologies.
Biomechanics as a sports science, kinesiology, applies the laws of mechanics and physics to human performance in order to gain a greater understanding of performance in athletic events through modeling, simulation, and measurement.
Continuum mechanics
It is often appropriate to model living tissues as continuous media. For example, at the tissue level, the arterial wall can be modeled as a continuum. This assumption breaks down when the length scales of interest approach the order of the micro structural details of the material. The basic postulates of continuum mechanics are conservation of linear and angular momentum, conservation of mass, conservation of energy, and the entropy inequality. Solids are usually modeled using "reference" or "Lagrangian" coordinates, whereas fluids are often modeled using "spatial" or "Eulerian" coordinates. Using these postulates and some assumptions regarding the particular problem at hand, a set of equilibrium equations can be established. The kinematics and constitutive relations are also needed to model a continuum
Second and fourth order tensors are crucial in representing many quantities in electromechanical. In practice, however, the full tensor form of a fourth-order constitutive matrix is rarely used. Instead, simplifications such as isotropy, transverse isotropy, and incompressibility reduce the number of independent components. Commonly-used second-order tensors include the Cauchy stress tensor, the second Piola-Kirchhoff stress tensor, the deformation gradient tensor, and the Green strain tensor. A reader of the mechanic's literature would be well-advised to note precisely the definitions of the various tensors which are being used in a particular work.
Biomechanics of circulation
Red blood cells
Under most circumstances, blood flow can be modeled by the Navier-Stokes equations. Whole blood can often be assumed to be an incompressible Newtonian fluid. However, this assumption fails when considering flows within arterioles. At this scale, the effects of individual red blood cells becomes significant, and whole blood can no longer be modeled as a continuum. When the diameter of the blood vessel is slightly larger than the diameter of the red blood cell the Fahraeus–Lindqvist effect occurs and there is a decrease in wall shear stress. However, as the diameter of the blood vessel decreases further, the red blood cells have to squeeze through the vessel and often can only pass in single file. In this case, the inverse Fahraeus–Lindqvist effect occurs and the wall shear stress increases.
Biomechanics of the bones
Bones are anisotropic but are approximately transversely isotropic. In other words, bones are stronger along one axis than across that axis, and are approximately the same strength no matter how they are rotated around that axis.
The stress-strain relations of bones can be modeled using Hooke's law, in which they are related by elastic moduli, e.g. Young's modulus, Poisson's ratio or the Lamé parameters. The constitutive matrix, a fourth order tensor, depends on the isotropy of the bone.
σij = Cijklεkl
Biomechanics of the muscle
There are three main types of muscles:
Skeletal muscle (striated): Unlike cardiac muscle, skeletal muscle can develop a sustained condition known as tetany through high frequency stimulation, resulting in overlapping twitches and a phenomenon known as wave summation. At a sufficiently high frequency, tetany occurs, and the contracticle force appears constant through time. This allows skeletal muscle to develop a wide variety of forces. This muscle type can be voluntary controlled. Hill's Model is the most popular model used to study muscle.
Cardiac muscle (striated): Cardiomyocytes are a highly specialized cell type. These involuntarily contracted cells are located in the heart wall and operate in concert to develop synchronized beats. This is attributable to a refractory period between twitches.
Smooth muscle (smooth - lacking striations): The stomach, vasculature, and most of the digestive tract are largely composed of smooth muscle. This muscle type is involuntary and is controlled by the enteric nervous system.
Biomechanics of soft tissues
Soft tissues such as tendon, ligament and cartilage are combinations of matrix proteins and fluid. In each of these tissues the main strength bearing element is collagen, although the amount and type of collagen varies according to the function each tissue must perform. Elastin is also a major load-bearing constituent within skin, the vasculature, and connective tissues. The function of tendons is to connect muscle with bone and is subjected to tensile loads. Tendons must be strong to facilitate movement of the body while at the same time remaining compliant to prevent damage to the muscle tissues. Ligaments connect bone to bone and therefore are stiffer than tendons but are relatively close in their tensile strength. Cartilage, on the other hand, is primarily loaded in compression and acts as a cushion in the joints to distribute loads between bones. The compressive strength of collagen is derived mainly from collagen as in tendons and ligaments, however because collagen is comparable to a "wet noodle" it must be supported by cross-links of glycosaminoglycans that also attract water and create a nearly incompressible tissue capable of supporting compressive loads.
Recently, research is growing on the biomechanics of other types of soft tissues such as skin and internal organs. This interest is spurred by the need for realism in the development of medical simulation.
Viscoelasticity
Viscoelasticity is readily evident in many soft tissues, where there is energy dissipation, or hysteresis, between the loading and unloading of the tissue during mechanical tests. Some soft tissues can be preconditioned by repetitive cyclic loading to the extent where the stress-strain curves for the loading and unloading portions of the tests nearly overlap. The most commonly used model for viscoelasticity is the Quasilinear Viscoelasticity theory (QLV).
Nonlinear theories
Hooke's law is linear, but many, if not most problems in biomechanics, involve highly nonlinear behavior, particularly for soft tissues. Proteins such as collagen and elastin, for example, exhibit such a behavior. Some common material models include the Neo-Hookean behavior, often used for modeling elastin, and the famous Fung-elastic exponential model. Non linear phenomena in the biomechanics of soft tissue arise not only from the material properties but also from the very large strains (100% and more) that are characteristic of many problems in soft tissues.
From Wikipedia, the free encyclopedia
Biomechanics is mechanics applied to biology (Fung). This includes research and analysis of the mechanics of living organisms and the application of engineering principles to and from biological systems. This research and analysis can be carried forth on multiple levels, from the molecular, wherein biomaterials such as collagen and elastin are considered, all the way up to the tissue and organ level. Some simple applications of Newtonian mechanics can supply correct approximations on each level, but precise details demand the use of continuum mechanics.
Chinstrap Penguin
Giovanni Alfonso Borelli wrote the first book on biomechanics, De Motu Animalium, or On the Movement of Animals. He not only saw animals' bodies as mechanical systems, but pursued questions such as the physiological difference between imagining performing an action and actually doing it. Some simple examples of biomechanics research include the investigation of the forces that act on limbs, the aerodynamics of bird and insect flight, the hydrodynamics of swimming in fish, the anchorage and mechanical support provided by tree roots, and locomotion in general across all forms of life, from individual cells to whole organisms. The biomechanics of human beings is a core part of kinesiology.
Applied mechanics, most notably thermodynamics and continuum mechanics, and mechanical engineering disciplines such as fluid mechanics and solid mechanics, play prominent roles in the study of biomechanics. By applying the laws and concepts of physics, biomechanical mechanisms and structures can be simulated and studied.
It has been shown that applied loads and deformations can affect the properties of living tissue. There is much research in the field of growth and remodeling as a response to applied loads. For example, the effects of elevated blood pressure on the mechanics of the arterial wall, the behavior of cardiomyocytes within a heart with a cardiac infarct, and bone growth in response to exercise, and the acclimative growth of plants in response to wind movement, have been widely regarded as instances in which living tissue is remodelled as a direct consequence of applied loads.
Relevant mathematical tools include linear algebra, differential equations, vector and tensor calculus, numerics and computational techniques such as the finite element method.
The study of biomaterials is of crucial importance to biomechanics. For example, the various tissues within the body, such as skin, bone, and arteries each possess unique material properties. The passive mechanical response of a particular tissue can be attributed to characteristics of the various proteins, such as elastin and collagen, living cells, ground substances such as proteoglycans, and the orientations of fibers within the tissue. For example, if human skin were largely composed of a protein other than collagen, many of its mechanical properties, such as its elastic modulus, would be different.
Chemistry, molecular biology, and cell biology have much to offer in the way of explaining the active and passive properties of living tissues. For example, in muscle contractions, the binding of myosin to actin is based on a biochemical reaction involving calcium ions and ATP.
Applications
The study of biomechanics ranges from the inner workings of a cell to the movement and development of limbs, to the mechanical properties of soft tissue, and bones. As we develop a greater understanding of the physiological behavior of living tissues, researchers are able to advance the field of tissue engineering, as well as develop improved treatments for a wide array of pathologies.
Biomechanics as a sports science, kinesiology, applies the laws of mechanics and physics to human performance in order to gain a greater understanding of performance in athletic events through modeling, simulation, and measurement.
Continuum mechanics
It is often appropriate to model living tissues as continuous media. For example, at the tissue level, the arterial wall can be modeled as a continuum. This assumption breaks down when the length scales of interest approach the order of the micro structural details of the material. The basic postulates of continuum mechanics are conservation of linear and angular momentum, conservation of mass, conservation of energy, and the entropy inequality. Solids are usually modeled using "reference" or "Lagrangian" coordinates, whereas fluids are often modeled using "spatial" or "Eulerian" coordinates. Using these postulates and some assumptions regarding the particular problem at hand, a set of equilibrium equations can be established. The kinematics and constitutive relations are also needed to model a continuum
Second and fourth order tensors are crucial in representing many quantities in electromechanical. In practice, however, the full tensor form of a fourth-order constitutive matrix is rarely used. Instead, simplifications such as isotropy, transverse isotropy, and incompressibility reduce the number of independent components. Commonly-used second-order tensors include the Cauchy stress tensor, the second Piola-Kirchhoff stress tensor, the deformation gradient tensor, and the Green strain tensor. A reader of the mechanic's literature would be well-advised to note precisely the definitions of the various tensors which are being used in a particular work.
Biomechanics of circulation
Red blood cells
Under most circumstances, blood flow can be modeled by the Navier-Stokes equations. Whole blood can often be assumed to be an incompressible Newtonian fluid. However, this assumption fails when considering flows within arterioles. At this scale, the effects of individual red blood cells becomes significant, and whole blood can no longer be modeled as a continuum. When the diameter of the blood vessel is slightly larger than the diameter of the red blood cell the Fahraeus–Lindqvist effect occurs and there is a decrease in wall shear stress. However, as the diameter of the blood vessel decreases further, the red blood cells have to squeeze through the vessel and often can only pass in single file. In this case, the inverse Fahraeus–Lindqvist effect occurs and the wall shear stress increases.
Biomechanics of the bones
Bones are anisotropic but are approximately transversely isotropic. In other words, bones are stronger along one axis than across that axis, and are approximately the same strength no matter how they are rotated around that axis.
The stress-strain relations of bones can be modeled using Hooke's law, in which they are related by elastic moduli, e.g. Young's modulus, Poisson's ratio or the Lamé parameters. The constitutive matrix, a fourth order tensor, depends on the isotropy of the bone.
σij = Cijklεkl
Biomechanics of the muscle
There are three main types of muscles:
Skeletal muscle (striated): Unlike cardiac muscle, skeletal muscle can develop a sustained condition known as tetany through high frequency stimulation, resulting in overlapping twitches and a phenomenon known as wave summation. At a sufficiently high frequency, tetany occurs, and the contracticle force appears constant through time. This allows skeletal muscle to develop a wide variety of forces. This muscle type can be voluntary controlled. Hill's Model is the most popular model used to study muscle.
Cardiac muscle (striated): Cardiomyocytes are a highly specialized cell type. These involuntarily contracted cells are located in the heart wall and operate in concert to develop synchronized beats. This is attributable to a refractory period between twitches.
Smooth muscle (smooth - lacking striations): The stomach, vasculature, and most of the digestive tract are largely composed of smooth muscle. This muscle type is involuntary and is controlled by the enteric nervous system.
Biomechanics of soft tissues
Soft tissues such as tendon, ligament and cartilage are combinations of matrix proteins and fluid. In each of these tissues the main strength bearing element is collagen, although the amount and type of collagen varies according to the function each tissue must perform. Elastin is also a major load-bearing constituent within skin, the vasculature, and connective tissues. The function of tendons is to connect muscle with bone and is subjected to tensile loads. Tendons must be strong to facilitate movement of the body while at the same time remaining compliant to prevent damage to the muscle tissues. Ligaments connect bone to bone and therefore are stiffer than tendons but are relatively close in their tensile strength. Cartilage, on the other hand, is primarily loaded in compression and acts as a cushion in the joints to distribute loads between bones. The compressive strength of collagen is derived mainly from collagen as in tendons and ligaments, however because collagen is comparable to a "wet noodle" it must be supported by cross-links of glycosaminoglycans that also attract water and create a nearly incompressible tissue capable of supporting compressive loads.
Recently, research is growing on the biomechanics of other types of soft tissues such as skin and internal organs. This interest is spurred by the need for realism in the development of medical simulation.
Viscoelasticity
Viscoelasticity is readily evident in many soft tissues, where there is energy dissipation, or hysteresis, between the loading and unloading of the tissue during mechanical tests. Some soft tissues can be preconditioned by repetitive cyclic loading to the extent where the stress-strain curves for the loading and unloading portions of the tests nearly overlap. The most commonly used model for viscoelasticity is the Quasilinear Viscoelasticity theory (QLV).
Nonlinear theories
Hooke's law is linear, but many, if not most problems in biomechanics, involve highly nonlinear behavior, particularly for soft tissues. Proteins such as collagen and elastin, for example, exhibit such a behavior. Some common material models include the Neo-Hookean behavior, often used for modeling elastin, and the famous Fung-elastic exponential model. Non linear phenomena in the biomechanics of soft tissue arise not only from the material properties but also from the very large strains (100% and more) that are characteristic of many problems in soft tissues.
From Wikipedia, the free encyclopedia
Biophysical techniques
Biophysical techniques are methods used for gaining information about biological systems on an atomic or molecular level. They overlap with methods from other branches of science.
Main biophysical techniques are:
Scientist using a stereo microscope outfitted with a digital imaging pick-up
Circular dichroism, a method for detecting chiral groups in molecules, especially to determine the secondary structure of proteins
Dual Polarisation Interferometry, an analytical technique used to understand the real-time structure and behaviour of a wide range of molecular systems and interactions through quantitative measurement.
Electron microscopy, to gain high-resolution images of subcellular structures
Fluorescence spectroscopy, which can be used to detect structural rearrangements, as well as interactions of biomolecules
Force spectroscopy probes the mechanical properties of individual molecules or macromolecular assemblies using small flexible cantilevers, focused laser light, or magnetic fields.
Gel electrophoresis, which is used to determine the mass, the charge and the interactions of biological molecules
Isothermal Titration Calorimetry or ITC which measure the heat effects caused by interactions
Mass spectrometry is a technique that gives the molecular mass with great accuracy.
Microscopy, for example using laser instruments for scanning and transmission.
Optical tweezers and Magnetic tweezers allow for the manipulation of single molecules, providing information about DNA and its interaction with proteins and molecular motors, such as Helicase and RNA polymerase.
NMR spectroscopy, giving information about the exact structure of biological molecules, as well as on dynamics
Single molecule spectroscopy is a general term applied to a class of techniques that are sensitive enough to detect single molecules and often incorporates fluorescence detection.
Small angle X-ray scattering (SAXS) is a technique that gives a rough low resolution molecular structure.
Spectrophotometry, the measurement of the transmission of light through different solutions or substances at different wavelengths of light. Colorimetry is an example of this.
Ultracentrifugation, which gives information on the shape and mass of molecules
various chromatography technique, which are used for the purification and analysis of biological molecules
X-ray crystallography, another method to gain access to the exact structure of molecules with atomic resolution
.From Wikipedia, the free encyclopedia
Main biophysical techniques are:
Scientist using a stereo microscope outfitted with a digital imaging pick-up
Circular dichroism, a method for detecting chiral groups in molecules, especially to determine the secondary structure of proteins
Dual Polarisation Interferometry, an analytical technique used to understand the real-time structure and behaviour of a wide range of molecular systems and interactions through quantitative measurement.
Electron microscopy, to gain high-resolution images of subcellular structures
Fluorescence spectroscopy, which can be used to detect structural rearrangements, as well as interactions of biomolecules
Force spectroscopy probes the mechanical properties of individual molecules or macromolecular assemblies using small flexible cantilevers, focused laser light, or magnetic fields.
Gel electrophoresis, which is used to determine the mass, the charge and the interactions of biological molecules
Isothermal Titration Calorimetry or ITC which measure the heat effects caused by interactions
Mass spectrometry is a technique that gives the molecular mass with great accuracy.
Microscopy, for example using laser instruments for scanning and transmission.
Optical tweezers and Magnetic tweezers allow for the manipulation of single molecules, providing information about DNA and its interaction with proteins and molecular motors, such as Helicase and RNA polymerase.
NMR spectroscopy, giving information about the exact structure of biological molecules, as well as on dynamics
Single molecule spectroscopy is a general term applied to a class of techniques that are sensitive enough to detect single molecules and often incorporates fluorescence detection.
Small angle X-ray scattering (SAXS) is a technique that gives a rough low resolution molecular structure.
Spectrophotometry, the measurement of the transmission of light through different solutions or substances at different wavelengths of light. Colorimetry is an example of this.
Ultracentrifugation, which gives information on the shape and mass of molecules
various chromatography technique, which are used for the purification and analysis of biological molecules
X-ray crystallography, another method to gain access to the exact structure of molecules with atomic resolution
.From Wikipedia, the free encyclopedia
Biophysics
Biophysics (also biological physics) is an interdisciplinary science that employs and develops theories and methods of the physical sciences for the investigation of biological systems. Studies included under the umbrella of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems. Biophysical research shares significant overlap with biochemistry, nanotechnology, bioengineering and systems biology.
Molecular biophysics typically addresses biological questions that are similar to those in biochemistry and molecular biology, but the questions are approached quantitatively. Scientists in this field conduct research concerned with understanding the interactions between the various systems of a cell, including the interactions between DNA, RNA and protein biosynthesis, as well as how these interactions are regulated. A great variety of techniques are used to answer these questions.
Fluorescent imaging techniques, as well as electron microscopy, x-ray crystallography and atomic force microscopy (AFM) are often used to visualize structures of biological significance. Direct manipulation of molecules using optical tweezers or AFM can also be used to monitor biological events where forces and distances are at the nanoscale. Molecular biophysicists often consider complex biological events as systems of interacting units which can be understood through statistical mechanics, thermodynamics and chemical kinetics. By drawing knowledge and experimental techniques from a wide variety of disciplines, biophysicists are often able to directly observe, model or even manipulate the structures and interactions of individual molecules or complexes of molecules.
In addition to traditional (i.e. molecular) biophysical topics like structural biology or enzyme kinetics, modern biophysics encompasses an extraordinarily broad range of research. It is becoming increasingly common for biophysicists to apply the models and experimental techniques derived from physics, as well as mathematics and statistics, to larger systems such as tissues, organs, populations and ecosystems.
Focus as a subfield
Biophysics often does not have university-level departments of its own, but have presence as groups across departments within the fields of biology, biochemistry, chemistry, computer science, mathematics, medicine, pharmacology, physiology, physics, and neuroscience. What follows is a list of examples of how each department applies its efforts toward the study of biophysics. This list is hardly all inclusive. Nor does each subject of study belong exclusively to any particular department. Each academic institution makes its own rules and there is much overlap between departments.
Biology and molecular biology - Almost all forms of biophysics efforts are included in some biology department somewhere. To include some: gene regulation, single protein dynamics, bioenergetics, patch clamping, biomechanics.
Structural biology - angstrom-resolution structures of proteins, nucleic acids, lipids, carbohydrates, and complexes thereof.
Biochemistry and chemistry - biomolecular structure, siRNA, nucleic acid structure, structure-activity relationships.
Computer science - Neural networks, Biomolecular and drug databases.
Computational chemistry - Molecular dynamics simulation, Molecular docking, Quantum chemistry
Bioinformatics - sequence alignment, structural alignment, Protein structure prediction
Mathematics - graph/network theory, population modeling, dynamical systems, phylogenetics.
Medicine and neuroscience - tackling neural networks experimentally (brain slicing) as well as theoretically (computer models), membrane permitivity, gene therapy, understanding tumors.
Pharmacology and physiology - channel biology, biomolecular interactions, cellular membranes, polyketides.
Physics - Biomolecular free energy, stochastic processes, covering dynamics.
Many biophysical techniques are unique to this field. Research efforts in biophysics are often initiated by scientists who were traditional physicists, chemists, and biologists by training
From Wikipedia, the free encyclopedia
Molecular biophysics typically addresses biological questions that are similar to those in biochemistry and molecular biology, but the questions are approached quantitatively. Scientists in this field conduct research concerned with understanding the interactions between the various systems of a cell, including the interactions between DNA, RNA and protein biosynthesis, as well as how these interactions are regulated. A great variety of techniques are used to answer these questions.
Fluorescent imaging techniques, as well as electron microscopy, x-ray crystallography and atomic force microscopy (AFM) are often used to visualize structures of biological significance. Direct manipulation of molecules using optical tweezers or AFM can also be used to monitor biological events where forces and distances are at the nanoscale. Molecular biophysicists often consider complex biological events as systems of interacting units which can be understood through statistical mechanics, thermodynamics and chemical kinetics. By drawing knowledge and experimental techniques from a wide variety of disciplines, biophysicists are often able to directly observe, model or even manipulate the structures and interactions of individual molecules or complexes of molecules.
In addition to traditional (i.e. molecular) biophysical topics like structural biology or enzyme kinetics, modern biophysics encompasses an extraordinarily broad range of research. It is becoming increasingly common for biophysicists to apply the models and experimental techniques derived from physics, as well as mathematics and statistics, to larger systems such as tissues, organs, populations and ecosystems.
Focus as a subfield
Biophysics often does not have university-level departments of its own, but have presence as groups across departments within the fields of biology, biochemistry, chemistry, computer science, mathematics, medicine, pharmacology, physiology, physics, and neuroscience. What follows is a list of examples of how each department applies its efforts toward the study of biophysics. This list is hardly all inclusive. Nor does each subject of study belong exclusively to any particular department. Each academic institution makes its own rules and there is much overlap between departments.
Biology and molecular biology - Almost all forms of biophysics efforts are included in some biology department somewhere. To include some: gene regulation, single protein dynamics, bioenergetics, patch clamping, biomechanics.
Structural biology - angstrom-resolution structures of proteins, nucleic acids, lipids, carbohydrates, and complexes thereof.
Biochemistry and chemistry - biomolecular structure, siRNA, nucleic acid structure, structure-activity relationships.
Computer science - Neural networks, Biomolecular and drug databases.
Computational chemistry - Molecular dynamics simulation, Molecular docking, Quantum chemistry
Bioinformatics - sequence alignment, structural alignment, Protein structure prediction
Mathematics - graph/network theory, population modeling, dynamical systems, phylogenetics.
Medicine and neuroscience - tackling neural networks experimentally (brain slicing) as well as theoretically (computer models), membrane permitivity, gene therapy, understanding tumors.
Pharmacology and physiology - channel biology, biomolecular interactions, cellular membranes, polyketides.
Physics - Biomolecular free energy, stochastic processes, covering dynamics.
Many biophysical techniques are unique to this field. Research efforts in biophysics are often initiated by scientists who were traditional physicists, chemists, and biologists by training
From Wikipedia, the free encyclopedia
Biochemistry
Wöhler observes the synthesis of urea.
Biochemistry (from Greek: βίος, bios, "life" and Egyptian kēme, "earth" is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids, and other biomolecules. Chemical biology aims to answer many questions arising from biochemistry by using tools developed within chemical synthesis.
Although there are a vast number of different biomolecules, many are complex and large molecules (called polymers) that are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types. For example, a protein is a polymer made up of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction.
This article only discusses terrestrial biochemistry (carbon- and water-based), as all the life forms we know are on Earth. Since life forms alive today descended from the same common ancestor, they have similar biochemistries, even for matters that seem to be essentially arbitrary, such as handedness of various biomolecules. It is unknown whether alternative biochemistries are possible or practical.
History
Friedrich Wöhler
Originally, it was generally believed that life was not subject to the laws of science the way non-life was. It was thought that only living beings could produce the molecules of life (from other, previously existing biomolecules). Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created artificially. The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term “biochemistry” seems to have been first used in 1882, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuberg, a German chemist. Previously, this area would have been referred to as physiological chemistry. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labeling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle).
Another significant historic event in biochemistry is the discovery of the gene and its role in the transfer of information in the cell. This part of biochemistry is often called molecular biology. In the 1950's, James D. Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins were instrumental in solving DNA structure and suggesting its relationship with genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, which led to growth of forensic science. More recently, Andrew Z. Fire and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference (RNAi), in the silencing of gene expression.
Today, there are three main types of biochemistry as established by Michael E. Sugar. Plant biochemistry involves the study of the biochemistry of autotrophic organisms such as photosynthesis and other plant specific biochemical processes. General biochemistry encompasses both plant and animal biochemistry. Human/medical/medicinal biochemistry focuses on the biochemistry of humans and medical illnesses.
Carbohydrates
The function of carbohydrates includes energy storage and providing structure. Sugars are carbohydrates, but not all carbohydrates are sugars. There are more carbohydrates on Earth than any other known type of biomolecule.
Monosaccharides
Glucose
The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOn, where n is at least 3). Glucose, one of the most important carbohydrates, is an example of a monosaccharide. So is fructose, the sugar that gives fruits their sweet taste. Some carbohydrates (especially after condensation to oligo- and polysaccharides) contain less carbon relative to H and O, which still are present in 2:1 (H:O) ratio. Monosaccharides can be grouped into aldoses (having an aldehyde group at the end of the chain, e. g. glucose) and ketoses (having a keto group in their chain; e. g. fructose). Both aldoses and ketoses occur in an equilibrium between the open-chain forms and (starting with chain lengths of C4) cyclic forms. These are generated by bond formation between one of the hydroxyl groups of the sugar chain with the carbon of the aldehyde or keto group to form a hemiacetal bond. This leads to saturated five-membered (in furanoses) or six-membered (in pyranoses) heterocyclic rings containing one O as heteroatom.
Disaccharides
Sucrose: ordinary table sugar and probably the most familiar carbohydrate.
Two monosaccharides can be joined together using dehydration synthesis, in which a hydrogen atom is removed from the end of one molecule and a hydroxyl group (—OH) is removed from the other; the remaining residues are then attached at the sites from which the atoms were removed. The H—OH or H2O is then released as a molecule of water, hence the term dehydration. The new molecule, consisting of two monosaccharides, is called a disaccharide and is conjoined together by a glycosidic or ether bond. The reverse reaction can also occur, using a molecule of water to split up a disaccharide and break the glycosidic bond; this is termed hydrolysis. The most well-known disaccharide is sucrose, ordinary sugar (in scientific contexts, called table sugar or cane sugar to differentiate it from other sugars). Sucrose consists of a glucose molecule and a fructose molecule joined together. Another important disaccharide is lactose, consisting of a glucose molecule and a galactose molecule. As most humans age, the production of lactase, the enzyme that hydrolyzes lactose back into glucose and galactose, typically decreases. This results in lactase deficiency, also called lactose intolerance.
Sugar polymers are characterised by having reducing or non-reducing ends. A reducing end of a carbohydrate is a carbon atom which can be in equilibrium with the open-chain aldehyde or keto form. If the joining of monomers takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an OH-side chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety form a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).
Oligosaccharides and polysaccharides
Cellulose as polymer of β-D-glucose
When a few (around three to six) monosaccharides are joined together, it is called an oligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers and signals, as well as having some other uses.
Many monosaccharides joined together make a polysaccharide. They can be joined together in one long linear chain, or they may be branched. Two of the most common polysaccharides are cellulose and glycogen, both consisting of repeating glucose monomers.
Cellulose is made by plants and is an important structural component of their cell walls. Humans can neither manufacture nor digest it.
Glycogen, on the other hand, is an animal carbohydrate; humans and other animals use it as a form of energy storage.
Use of carbohydrates as an energy source
Glucose is the major energy source in most life forms. For instance, polysaccharides are broken down into their monomers (glycogen phosphorylase removes glucose residues from glycogen). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides.
Glycolysis (anaerobic)
Glucose is mainly metabolized by a very important and ancient ten-step pathway called glycolysis, the net result of which is to break down one molecule of glucose into two molecules of pyruvate; this also produces a net two molecules of ATP, the energy currency of cells, along with two reducing equivalents in the form of converting NAD+ to NADH. This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate to lactate (lactic acid) (e. g. in humans) or to ethanol plus carbon dioxide (e. g. in yeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway.
Aerobic
In aerobic cells with sufficient oxygen, like most human cells, the pyruvate is further metabolized. It is irreversibly converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric acid cycle, producing two more molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via FADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thereby, oxygen is reduced to water and the original electron acceptors NAD+ and quinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional 28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle). It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of oxygen.
Gluconeogenesis
In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate. The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides.
Proteins
A schematic of hemoglobin. The red and blue ribbons represent the protein globin; the green structures are the heme groups.
Like carbohydrates, some proteins perform largely structural roles. For instance, movements of the proteins actin and myosin ultimately are responsible for the contraction of skeletal muscle. One property many proteins have is that they specifically bind to a certain molecule or class of molecules—they may be extremely selective in what they bind. Antibodies are an example of proteins that attach to one specific type of molecule. In fact, the enzyme-linked immunosorbent assay (ELISA), which uses antibodies, is currently one of the most sensitive tests modern medicine uses to detect various biomolecules. Probably the most important proteins, however, are the enzymes. These amazing molecules recognize specific reactant molecules called substrates; they then catalyze the reaction between them. By lowering the activation energy, the enzyme speeds up that reaction by a rate of 1011 or more: a reaction that would normally take over 3,000 years to complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the process, and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole.
In essence, proteins are chains of amino acids. An amino acid consists of a carbon atom bound to four groups. One is an amino group, —NH2, and one is a carboxylic acid group, —COOH (although these exist as —NH3+ and —COO− under physiologic conditions). The third is a simple hydrogen atom. The fourth is commonly denoted "—R" and is different for each amino acid. There are twenty standard amino acids. Some of these have functions by themselves or in a modified form; for instance, glutamate functions as an important neurotransmitter.
Generic amino acids in neutral form, as they exist physiologically, and joined together as a dipeptide.
Amino acids can be joined together via a peptide bond. In this dehydration synthesis, a water molecule is removed and the peptide bond connects the nitrogen of one amino acid's amino group to the carbon of the other's carboxylic acid group. The resulting molecule is called a dipeptide, and short stretches of amino acids (usually, fewer than around thirty) are called peptides or polypeptides. Longer stretches merit the title proteins. As an example, the important blood serum protein albumin contains 585 amino acid residues.
The structure of proteins is traditionally described in a hierarchy of four levels. The primary structure of a protein simply consists of its linear sequence of amino acids; for instance, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-…". Secondary structure is concerned with local morphology. Some combinations of amino acids will tend to curl up in a coil called an α-helix or into a sheet called a β-sheet; some α-helixes can be seen in the hemoglobin schematic above. Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin contains 146 amino acid residues; substitution of the glutamate residue at position 6 with a valine residue changes the behavior of hemoglobin so much that it results in sickle-cell disease. Finally quaternary structure is concerned with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins have more than one subunit.
Ingested proteins are usually broken up into single amino acids or dipeptides in the small intestine, and then absorbed. They can then be joined together to make new proteins. Intermediate products of glycolysis, the citric acid cycle, and the pentose phosphate pathway can be used to make all twenty amino acids, and most bacteria and plants possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can only synthesize half of them. They cannot synthesize isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These are the essential amino acids, since it is essential to ingest them. Mammals do possess the enzymes to synthesize alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine, the nonessential amino acids. While they can synthesize arginine and histidine, they cannot produce it in sufficient amounts for young, growing animals, and so these are often considered essential amino acids.
If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid. Enzymes called transaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an amino group is added, often via transamination. The amino acids may then be linked together to make a protein.
A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Free ammonia (NH3), existing as the ammonium ion (NH4+) in blood, is toxic to life forms. A suitable method for excreting it must therefore exist. Different strategies have evolved in different animals, depending on the animals' needs. Unicellular organisms, of course, simply release the ammonia into the environment. Similarly, bony fish can release the ammonia into the water where it is quickly diluted. In general, mammals convert the ammonia into urea, via the urea cycle.
Lipids
The term lipid comprises a diverse range of molecules and to some extent is a catchall for relatively water-insoluble or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids, sphingolipids, glycolipids and terpenoids (eg. retinoids and steroids). Some lipids are linear aliphatic molecules, while others have ring structures. Some are aromatic, while others are not. Some are flexible, while others are rigid.
Most lipids have some polar character in addition to being largely nonpolar. Generally, the bulk of their structure is nonpolar or hydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents like water. Another part of their structure is polar or hydrophilic ("water-loving") and will tend to associate with polar solvents like water. This makes them amphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case of cholesterol, the polar group is a mere -OH (hydroxyl or alcohol). In the case of phospholipids, the polar groups are considerably larger and more polar, as described below.
Lipids are an integral part of our daily diet. Most oils and milk products that we use for cooking and eating like butter, cheese, ghee etc, are comprised of fats. Vegetable oils are rich in various polyunsaturated fatty acids (PUFA). Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, which are the final degradation products of fats and lipids.
Nucleic acids
A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that convey genetic information. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are found in all living cells and viruses. Aside from the genetic material of the cell, nucleic acids often play a role as second messengers, as well as forming the base molecule for adenosine triphosphate, the primary energy-carrier molecule found in all living organisms.
Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of the family of biopolymers. The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2-deoxyriboses). Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while thymine occurs only in DNA and uracil occurs in RNA.
Relationship to other "molecular-scale" biological sciences
Schematic relationship between biochemistry, genetics and molecular biology
Researchers in biochemistry use specific techniques native to biochemistry, but increasingly combine these with techniques and ideas from genetics, molecular biology and biophysics. There has never been a hard-line between these disciplines in terms of content and technique, but members of each discipline have in the past been very territorial; today the terms molecular biology and biochemistry are nearly interchangeable. The following figure is a schematic that depicts one possible view of the relationship between the fields:
Biochemistry is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry.
Genetics is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies.
Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA.
Chemical Biology seeks to develop new tools based on small molecules that allow minimal perturbation of biological systems while providing detailed information about their function. Further, chemical biology employs biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example emptied viral capsids that can deliver gene therapy or drug molecules).
From Wikipedia, the free encyclopedia
Biochemistry (from Greek: βίος, bios, "life" and Egyptian kēme, "earth" is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids, and other biomolecules. Chemical biology aims to answer many questions arising from biochemistry by using tools developed within chemical synthesis.
Although there are a vast number of different biomolecules, many are complex and large molecules (called polymers) that are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types. For example, a protein is a polymer made up of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction.
This article only discusses terrestrial biochemistry (carbon- and water-based), as all the life forms we know are on Earth. Since life forms alive today descended from the same common ancestor, they have similar biochemistries, even for matters that seem to be essentially arbitrary, such as handedness of various biomolecules. It is unknown whether alternative biochemistries are possible or practical.
History
Friedrich Wöhler
Originally, it was generally believed that life was not subject to the laws of science the way non-life was. It was thought that only living beings could produce the molecules of life (from other, previously existing biomolecules). Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created artificially. The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term “biochemistry” seems to have been first used in 1882, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuberg, a German chemist. Previously, this area would have been referred to as physiological chemistry. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labeling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle).
Another significant historic event in biochemistry is the discovery of the gene and its role in the transfer of information in the cell. This part of biochemistry is often called molecular biology. In the 1950's, James D. Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins were instrumental in solving DNA structure and suggesting its relationship with genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, which led to growth of forensic science. More recently, Andrew Z. Fire and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference (RNAi), in the silencing of gene expression.
Today, there are three main types of biochemistry as established by Michael E. Sugar. Plant biochemistry involves the study of the biochemistry of autotrophic organisms such as photosynthesis and other plant specific biochemical processes. General biochemistry encompasses both plant and animal biochemistry. Human/medical/medicinal biochemistry focuses on the biochemistry of humans and medical illnesses.
Carbohydrates
The function of carbohydrates includes energy storage and providing structure. Sugars are carbohydrates, but not all carbohydrates are sugars. There are more carbohydrates on Earth than any other known type of biomolecule.
Monosaccharides
Glucose
The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOn, where n is at least 3). Glucose, one of the most important carbohydrates, is an example of a monosaccharide. So is fructose, the sugar that gives fruits their sweet taste. Some carbohydrates (especially after condensation to oligo- and polysaccharides) contain less carbon relative to H and O, which still are present in 2:1 (H:O) ratio. Monosaccharides can be grouped into aldoses (having an aldehyde group at the end of the chain, e. g. glucose) and ketoses (having a keto group in their chain; e. g. fructose). Both aldoses and ketoses occur in an equilibrium between the open-chain forms and (starting with chain lengths of C4) cyclic forms. These are generated by bond formation between one of the hydroxyl groups of the sugar chain with the carbon of the aldehyde or keto group to form a hemiacetal bond. This leads to saturated five-membered (in furanoses) or six-membered (in pyranoses) heterocyclic rings containing one O as heteroatom.
Disaccharides
Sucrose: ordinary table sugar and probably the most familiar carbohydrate.
Two monosaccharides can be joined together using dehydration synthesis, in which a hydrogen atom is removed from the end of one molecule and a hydroxyl group (—OH) is removed from the other; the remaining residues are then attached at the sites from which the atoms were removed. The H—OH or H2O is then released as a molecule of water, hence the term dehydration. The new molecule, consisting of two monosaccharides, is called a disaccharide and is conjoined together by a glycosidic or ether bond. The reverse reaction can also occur, using a molecule of water to split up a disaccharide and break the glycosidic bond; this is termed hydrolysis. The most well-known disaccharide is sucrose, ordinary sugar (in scientific contexts, called table sugar or cane sugar to differentiate it from other sugars). Sucrose consists of a glucose molecule and a fructose molecule joined together. Another important disaccharide is lactose, consisting of a glucose molecule and a galactose molecule. As most humans age, the production of lactase, the enzyme that hydrolyzes lactose back into glucose and galactose, typically decreases. This results in lactase deficiency, also called lactose intolerance.
Sugar polymers are characterised by having reducing or non-reducing ends. A reducing end of a carbohydrate is a carbon atom which can be in equilibrium with the open-chain aldehyde or keto form. If the joining of monomers takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an OH-side chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety form a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).
Oligosaccharides and polysaccharides
Cellulose as polymer of β-D-glucose
When a few (around three to six) monosaccharides are joined together, it is called an oligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers and signals, as well as having some other uses.
Many monosaccharides joined together make a polysaccharide. They can be joined together in one long linear chain, or they may be branched. Two of the most common polysaccharides are cellulose and glycogen, both consisting of repeating glucose monomers.
Cellulose is made by plants and is an important structural component of their cell walls. Humans can neither manufacture nor digest it.
Glycogen, on the other hand, is an animal carbohydrate; humans and other animals use it as a form of energy storage.
Use of carbohydrates as an energy source
Glucose is the major energy source in most life forms. For instance, polysaccharides are broken down into their monomers (glycogen phosphorylase removes glucose residues from glycogen). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides.
Glycolysis (anaerobic)
Glucose is mainly metabolized by a very important and ancient ten-step pathway called glycolysis, the net result of which is to break down one molecule of glucose into two molecules of pyruvate; this also produces a net two molecules of ATP, the energy currency of cells, along with two reducing equivalents in the form of converting NAD+ to NADH. This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate to lactate (lactic acid) (e. g. in humans) or to ethanol plus carbon dioxide (e. g. in yeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway.
Aerobic
In aerobic cells with sufficient oxygen, like most human cells, the pyruvate is further metabolized. It is irreversibly converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric acid cycle, producing two more molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via FADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thereby, oxygen is reduced to water and the original electron acceptors NAD+ and quinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional 28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle). It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of oxygen.
Gluconeogenesis
In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate. The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides.
Proteins
A schematic of hemoglobin. The red and blue ribbons represent the protein globin; the green structures are the heme groups.
Like carbohydrates, some proteins perform largely structural roles. For instance, movements of the proteins actin and myosin ultimately are responsible for the contraction of skeletal muscle. One property many proteins have is that they specifically bind to a certain molecule or class of molecules—they may be extremely selective in what they bind. Antibodies are an example of proteins that attach to one specific type of molecule. In fact, the enzyme-linked immunosorbent assay (ELISA), which uses antibodies, is currently one of the most sensitive tests modern medicine uses to detect various biomolecules. Probably the most important proteins, however, are the enzymes. These amazing molecules recognize specific reactant molecules called substrates; they then catalyze the reaction between them. By lowering the activation energy, the enzyme speeds up that reaction by a rate of 1011 or more: a reaction that would normally take over 3,000 years to complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the process, and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole.
In essence, proteins are chains of amino acids. An amino acid consists of a carbon atom bound to four groups. One is an amino group, —NH2, and one is a carboxylic acid group, —COOH (although these exist as —NH3+ and —COO− under physiologic conditions). The third is a simple hydrogen atom. The fourth is commonly denoted "—R" and is different for each amino acid. There are twenty standard amino acids. Some of these have functions by themselves or in a modified form; for instance, glutamate functions as an important neurotransmitter.
Generic amino acids in neutral form, as they exist physiologically, and joined together as a dipeptide.
Amino acids can be joined together via a peptide bond. In this dehydration synthesis, a water molecule is removed and the peptide bond connects the nitrogen of one amino acid's amino group to the carbon of the other's carboxylic acid group. The resulting molecule is called a dipeptide, and short stretches of amino acids (usually, fewer than around thirty) are called peptides or polypeptides. Longer stretches merit the title proteins. As an example, the important blood serum protein albumin contains 585 amino acid residues.
The structure of proteins is traditionally described in a hierarchy of four levels. The primary structure of a protein simply consists of its linear sequence of amino acids; for instance, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-…". Secondary structure is concerned with local morphology. Some combinations of amino acids will tend to curl up in a coil called an α-helix or into a sheet called a β-sheet; some α-helixes can be seen in the hemoglobin schematic above. Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin contains 146 amino acid residues; substitution of the glutamate residue at position 6 with a valine residue changes the behavior of hemoglobin so much that it results in sickle-cell disease. Finally quaternary structure is concerned with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins have more than one subunit.
Ingested proteins are usually broken up into single amino acids or dipeptides in the small intestine, and then absorbed. They can then be joined together to make new proteins. Intermediate products of glycolysis, the citric acid cycle, and the pentose phosphate pathway can be used to make all twenty amino acids, and most bacteria and plants possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can only synthesize half of them. They cannot synthesize isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These are the essential amino acids, since it is essential to ingest them. Mammals do possess the enzymes to synthesize alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine, the nonessential amino acids. While they can synthesize arginine and histidine, they cannot produce it in sufficient amounts for young, growing animals, and so these are often considered essential amino acids.
If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid. Enzymes called transaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an amino group is added, often via transamination. The amino acids may then be linked together to make a protein.
A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Free ammonia (NH3), existing as the ammonium ion (NH4+) in blood, is toxic to life forms. A suitable method for excreting it must therefore exist. Different strategies have evolved in different animals, depending on the animals' needs. Unicellular organisms, of course, simply release the ammonia into the environment. Similarly, bony fish can release the ammonia into the water where it is quickly diluted. In general, mammals convert the ammonia into urea, via the urea cycle.
Lipids
The term lipid comprises a diverse range of molecules and to some extent is a catchall for relatively water-insoluble or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids, sphingolipids, glycolipids and terpenoids (eg. retinoids and steroids). Some lipids are linear aliphatic molecules, while others have ring structures. Some are aromatic, while others are not. Some are flexible, while others are rigid.
Most lipids have some polar character in addition to being largely nonpolar. Generally, the bulk of their structure is nonpolar or hydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents like water. Another part of their structure is polar or hydrophilic ("water-loving") and will tend to associate with polar solvents like water. This makes them amphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case of cholesterol, the polar group is a mere -OH (hydroxyl or alcohol). In the case of phospholipids, the polar groups are considerably larger and more polar, as described below.
Lipids are an integral part of our daily diet. Most oils and milk products that we use for cooking and eating like butter, cheese, ghee etc, are comprised of fats. Vegetable oils are rich in various polyunsaturated fatty acids (PUFA). Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, which are the final degradation products of fats and lipids.
Nucleic acids
A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that convey genetic information. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are found in all living cells and viruses. Aside from the genetic material of the cell, nucleic acids often play a role as second messengers, as well as forming the base molecule for adenosine triphosphate, the primary energy-carrier molecule found in all living organisms.
Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of the family of biopolymers. The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2-deoxyriboses). Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while thymine occurs only in DNA and uracil occurs in RNA.
Relationship to other "molecular-scale" biological sciences
Schematic relationship between biochemistry, genetics and molecular biology
Researchers in biochemistry use specific techniques native to biochemistry, but increasingly combine these with techniques and ideas from genetics, molecular biology and biophysics. There has never been a hard-line between these disciplines in terms of content and technique, but members of each discipline have in the past been very territorial; today the terms molecular biology and biochemistry are nearly interchangeable. The following figure is a schematic that depicts one possible view of the relationship between the fields:
Biochemistry is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry.
Genetics is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies.
Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA.
Chemical Biology seeks to develop new tools based on small molecules that allow minimal perturbation of biological systems while providing detailed information about their function. Further, chemical biology employs biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example emptied viral capsids that can deliver gene therapy or drug molecules).
From Wikipedia, the free encyclopedia
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