coenzyme(redirected from Enzymatic cofactor)
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coenzyme(kō-ĕn`zīm), any one of a group of relatively small organic molecules required for the catalytic function of certain enzymesenzyme,
biological catalyst. The term enzyme comes from zymosis, the Greek word for fermentation, a process accomplished by yeast cells and long known to the brewing industry, which occupied the attention of many 19th-century chemists.
..... Click the link for more information. . A coenzyme may either be attached by covalent bonds to a particular enzyme or exist freely in solution, but in either case it participates intimately in the chemical reactions catalyzed by the enzyme. Often a coenzyme is structurally altered in the course of these reactions, but it is always restored to its original form in subsequent reactions catalyzed by other enzyme systems.
Adenosine triphosphateadenosine triphosphate
(ATP) , organic compound composed of adenine, the sugar ribose, and three phosphate groups. ATP serves as the major energy source within the cell to drive a number of biological processes such as photosynthesis, muscle contraction, and the synthesis of
..... Click the link for more information. (ATP) is a coenzyme of vast importance in the transfer of chemical energy derived from biochemical oxidations. Other nucleotidesnucleotide
, organic substance that serves as a monomer in forming nucleic acids. Nucleotides consist of either a purine or a pyrimidine base, a ribose or deoxyribose, and a phosphate group. Adenosine triphosphate serves as the principle energy carrier for the cell's reactions.
..... Click the link for more information. (formed from uraciluracil
, organic base of the pyrimidine family. It was isolated from herring sperm and also produced in a laboratory in 1900–1901. When combined with the sugar ribose in a glycosidic linkage, uracil forms a derivative called uridine (a nucleoside), which in turn can be
..... Click the link for more information. , cytosinecytosine
, organic base of the pyrimidine family. It was isolated from the nucleic acid of calf thymus tissue in 1894. A suggested structure for cytosine, published in 1903, was confirmed in the same year when that base was synthesized in the laboratory.
..... Click the link for more information. , guanineguanine
, organic base of the purine family. It was reported (1846) to be in the guano of birds; later (1879–84) it was established as one of the major constituents of nucleic acids.
..... Click the link for more information. , and inosine) have also been found to act as coenzymes. For example, uridine triphosphate—a derivative of uracil—has been demonstrated to be of great importance in the metabolism of carbohydrates, as in the biosynthesis of glycogen and sucrose.
Those coenzymes that have been found to be necessary in the diet are vitaminsvitamin,
group of organic substances that are required in the diet of humans and animals for normal growth, maintenance of life, and normal reproduction. Vitamins act as catalysts; very often either the vitamins themselves are coenzymes, or they form integral parts of coenzymes.
..... Click the link for more information. . One such compound, biotin, is a member of the B complex; it was first isolated in 1935 from dried egg yolk, and its structure was established in 1942. Biotin is usually found attached to a lysine residue in certain enzymes, where it participates in reactions involving the transfer of carboxyl (−COOH) groups; one such reaction is essential for the synthesis of fatty acids.
Another group of coenzymes is the cobalamin family; one member, cyanocobalamin (vitamin B12) is known to be essential in the diet, although its role in metabolism remains obscure. Closely related cobalamins seem to be involved in the biosynthesis of methionine and methane. The complicated cyanocobalamin molecule was reported in 1973 to have been synthesized; it was first isolated from liver some 25 years prior to that date.
Coenzyme A has been shown to participate in a variety of biochemical reactions, all involving acyl groups such as the acetyl unit; it is, for instance, associated with the pivotal first step of the Krebs cycleKrebs cycle,
series of chemical reactions carried out in the living cell; in most higher animals, including humans, it is essential for the oxidative metabolism of glucose and other simple sugars.
..... Click the link for more information. , in which an acetyl unit (the breakdown product of carbohydrates) is introduced into the cycle to be converted eventually into carbon dioxide, water, and chemical energy. Coenzyme A is derived from adenine, ribose, and pantothenic acid (a vitamin of the B complex).
The two flavin coenzymes, riboflavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), occur universally in living organisms and play important roles in biochemical oxidations and reductions. They are usually found tightly bound to certain enzymes (flavoproteins) and are derived from riboflavin (vitamin B2).
Glutathione, a tripeptide consisting of residues of glutamic acid, cysteine, and glycine, is known to act as a coenzyme in a few enzymatic reactions, but its importance may lie in its role as a nonspecific reducing agent within the cell. It is hypothesized that glutathione serves to maintain the biological activity of certain proteins by keeping selected cysteine sidechains in the reduced thiol form, thereby not allowing these residues to oxidize and cross-link with one another to form cystine residues. (Unnecessary cross-links often result in distortions of protein structure.)
Heme, a complicated molecule containing iron in the ferrous state, serves as a coenzyme in a variety of biochemical processes. It forms an essential part of the structure of hemoglobinhemoglobin
, respiratory protein found in the red blood cells (erythrocytes) of all vertebrates and some invertebrates. A hemoglobin molecule is composed of a protein group, known as globin, and four heme groups, each associated with an iron atom.
..... Click the link for more information. and participates intimately in the uptake and release of oxygen by this protein. (In this case the use of the word coenzyme may be inappropriate in that often hemoglobin is not considered to be an enzyme, since it does not catalyze a chemical reaction.) Heme is an important part of the cytochromescytochrome
, protein containing heme (see coenzyme) that participates in the phase of biochemical respiration called oxidative phosphorylation. Cytochromes act as carriers of hydride ions (sometimes considered to be the equivalent of electron pairs) in the series of complex
..... Click the link for more information. , enzymes that catalyze the biochemical oxidations and reductions involved in the production of chemical energy in the form of ATP; heme is also associated with the various enzymes that catalyze the cleavage of peroxides.
Lipoic acid seems to be involved in the removal of carboxyl groups from α-keto acids and in the transfer of the remaining acyl groups to various acceptors. Lipoic acid in fact transfers the acetyl group of pyruvic acid to coenzyme A. Like biotin, lipoic acid is commonly found attached to lysine residues within certain enzymes. It was first reported to have been purified and isolated in crystalline form in 1953.
The nicotinamide nucleotides were the first coenzymes to be detected (1904) in extracts of a living organism. Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are derived from adenine, ribose, and nicotinic acid or niacin (a vitamin of the B complex) and are important intermediates in the biochemical oxidations and reductions that provide chemical energy within the cell. Both NAD and NADP can be reduced by accepting a hydride ion (H−, a proton with two electrons) from an appropriate donor; the resulting NADH and NADPH can then be oxidized back to their original states by transferring their hydride ions to various acceptors. In this fashion electron pairs (and protons) are shuttled about in the cell from high-energy donors to lower-energy acceptors. As a general rule, NADPH donates its hydride ions to biosynthetic processes, such as the fixing of carbon dioxide to make carbohydrates during the dark reaction of photosynthesis. NADH, on the other hand, donates its hydride ions to systems such as the cytochromes, which eventually donate them to oxygen to make (with the addition of a proton) water, producing chemical energy in the form of ATP as a byproduct; the process is not yet completely understood.
Pyridoxal phosphate is a coenzyme that is essential for many enzymatic reactions, almost all of which are associated with amino acid metabolism. It is, for example, involved in the synthesis of tryptophan, a derivative of pyridoxine (another vitamin of the B complex).
The coenzyme tetrahydrofolic acid is derived in humans from the B-complex vitamin folic acid. This coenzyme and its close relatives participate in the transfer of various carbon fragments from one molecule to another; they are, for instance, involved in the synthesis of methionine and thymine.
Thiamine pyrophosphate is derived from another B-complex vitamin, thiamine. This coenzyme often plays a role in the removal of carboxyl (−COOH) groups from organic acids, releasing the carbon and oxygen atoms as carbon dioxide (CO2). This coenzyme, for example, helps to remove a carboxyl group from pyruvic acid, leaving behind an acetyl group, which it donates to lipoic acid; the lipoic acid then transfers the acetyl group to coenzyme A, which finally inserts it into the beginning of the Krebs cycle. This important three-step enzymatic process requires the participation of three coenzymes; hundreds of other biochemical reactions require coenzymes as well, and this serves to explain the great significance of those molecules in the functioning of living organisms. In the case of human beings, it also serves to explain the importance of proper dietary intake of vitamins, which provide the only source of certain "building blocks" for several of these coenzymes.
An organic cofactor or prosthetic group (nonprotein portion of the enzyme) whose presence is required for the activity of many enzymes. The prosthetic groups attached to the protein of the enzyme (the apoenzyme) may be regarded as dissociable portions of conjugated proteins. Neither the apoenzyme nor the coenzyme moieties can function singly. In general, the coenzymes function as acceptors of electrons or functional groupings, such as the carboxyl groups in α-keto acids, which are removed from the substrate. See Protein
Well-known coenzymes include the pyridine nucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP); thiamine pyrophosphate (TPP); flavin mononucleotide (FMN) and flavinadenine dinucleotide (FAD); iron protoporphyrin (hemin); uridine diphosphate (UDP) and UDP-glucose; and adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Coenzyme A (CoA), a coenzyme in certain condensing enzymes, acts in acetyl or other acyl group transfer and in fatty acid synthesis and oxidation. Folic acid coenzymes are involved in the metabolism of one carbon unit. Biotin is the coenzyme in a number of carboxylation reactions, where it functions as the actual carrier of carbon dioxide. See Adenosine diphosphate (ADP), Adenosine triphosphate (ATP), Biotin, Enzyme, Hemoglobin, Nicotinamide adenine dinucleotide (NAD), Nicotinamide adenine dinucleotide phosphate (NADP)