Coenzyme
Coenzymes are small organic non-protein molecules that carry chemical groups between enzymes.[1] They are substrates for enzymes and do not form a permanent part of the enzymes' structures. This distinguishes coenzymes from cofactors, which are non-protein components that are bound to enzymes - such as iron-sulfur centers, flavin or haem groups.
In metabolism, coenzymes are involved in both group-transfer reactions, for example coenzyme A and adenosine triphosphate, and redox reactions, for example coenzyme Q10 and nicotinamide adenine dinucleotide. These molecules are often vitamins or are made from vitamins.
Terminology
The term coenzymes is commonly used loosely, and coenzymes can also be defined as organic, non-protein cofactors.[2] Coenzymes are also sometimes referred to as cosubstrates, but this usage is unusual.
Coenzymes are consumed in the reactions in which they are substrates, for example: the coenzyme NADH is converted to NAD+ by oxidoreductases. Coenzymes are however regenerated and their concentration maintained at a steady level in the cell.
A special subset of coenzymes are prosthetic groups. These have more in common with cofactors since they are tightly bound to enzymes and are not released as part of the reaction. Prosthetic groups include molybdopterin, lipoamide and biotin.
Coenzymes as metabolic intermediates
Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups.[3] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions.[4] These group-transfer intermediates are the coenzymes.
Each class of group-transfer reaction is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. An example of this are the dehydrogenases that use nicotinamide adenine dinucleotide (NADH) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NADH and this reduced coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.[5]
Types
Many coenzymes are phosphorylated water-soluble vitamins. Coenzymes are also commonly made from nucleotides such as adenosine triphosphate, the biochemical carrier of phosphate groups, or coenzyme A, the coenzyme that carries acyl groups.
Vitamin and nucleotide derivatives
Vitamin B family:
| Coenzyme | Vitamin | Additional component |
| Thiamine pyrophosphate | thiamine (B1) | - |
| FAD and FMN | riboflavin (B2) | - |
| NAD and NADP | niacin (B3) | nucleotide |
| Coenzyme A | pantothenic acid (B5) | ATP |
| Tetrahydrofolic acid | folic acid (B9) | - |
| Coenzyme B12 | B12 | - |
Not related to vitamins
- Coenzyme Q. (Coenzyme Q is unusual as it carries electrons between enzymes by diffusing within cell membranes, as this coenzyme is not water soluble. )
- Molybdopterin (sometimes considered a cofactor)[6]
Evolution
Coenzymes such as ATP and NAD(P)H form a core of metabolism that are present in all known forms of life. Such universal conservation indicates that these molecules evolved very early in the development of living things.[7] The current set of coenzymes were therefore probably present in the last universal ancestor, which lived about 4 billion years ago.[8][9]
Coenzymes may even have been present earlier in the history of life on Earth. Interestingly, the nucleotide adenosine is present in coenzymes that catalyse many basic metabolic reactions such as methyl, acyl, and phosphoryl group transfer and redox reactions. This ubiquitous chemical scaffold has been hypothesised to be a remnant of the RNA world, with early ribozymes evolving to bind a restricted set of nucleotides and related compounds.[10][11] Adenosine-based coenzymes are thought to have acted as interchangeable adaptors that allowed enzymes and ribozymes to bind new coenzymes through small modifications in existing adenosine-binding domains, which had evolved to bind a different cofactor.[12]
See also
References
- ^ de Bolster, M.W.G. (1997). "Glossary of Terms Used in Bioinorganic Chemistry". International Union of Pure and Applied Chemistry. Retrieved 2007-10-30.
- ^ Nelson, David L. (2005). Lehninger Principles of Biochemistry. New York: W. H. Freeman and company. p. 841. ISBN 0-7167-4339-6.
{{cite book}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Mitchell P (1979). "The Ninth Sir Hans Krebs Lecture. Compartmentation and communication in living systems. Ligand conduction: a general catalytic principle in chemical, osmotic and chemiosmotic reaction systems". Eur J Biochem. 95 (1): 1–20. PMID 378655.
- ^ Wimmer M, Rose I. "Mechanisms of enzyme-catalyzed group transfer reactions". Annu Rev Biochem. 47: 1031–78. PMID 354490.
- ^ Pollak N, Dölle C, Ziegler M (2007). "The power to reduce: pyridine nucleotides--small molecules with a multitude of functions". Biochem J. 402 (2): 205–18. PMID 17295611.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Mendel RR (2007). "Biology of the molybdenum cofactor". J. Exp. Bot. 58 (9): 2289–96. doi:10.1093/jxb/erm024. PMID 17351249.
- ^ Chen X, Li N, Ellington AD (2007). "Ribozyme catalysis of metabolism in the RNA world". Chem. Biodivers. 4 (4): 633–55. PMID 17443876.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Koch A (1998). "How did bacteria come to be?". Adv Microb Physiol. 40: 353–99. PMID 9889982.
- ^ Ouzounis C, Kyrpides N (1996). "The emergence of major cellular processes in evolution". FEBS Lett. 390 (2): 119–23. PMID 8706840.
- ^ Saran D, Frank J, Burke DH (2003). "The tyranny of adenosine recognition among RNA aptamers to coenzyme A". BMC Evol. Biol. 3: 26. PMID 14687414.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Jadhav VR, Yarus M (2002). "Coenzymes as coribozymes". Biochimie. 84 (9): 877–88. PMID 12458080.
- ^ Denessiouk KA, Rantanen VV, Johnson MS (2001). "Adenine recognition: a motif present in ATP-, CoA-, NAD-, NADP-, and FAD-dependent proteins". Proteins. 44 (3): 282–91. PMID 11455601.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- Examples at City University of New York
- Overview at National Institutes of Health
- Coenzymes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)