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
GlucoseThe 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).
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