Coenzyme

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Contents

* 1 Overview
* 2 Coenzymes as metabolic intermediates
* 3 Types
* 3.1 Vitamins and derivatives
* 3.2 Non-vitamins
* 4 Evolution
* 5 History
* 6 See also
* 7 References
* 8 External links

## Overview

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Coenzyme A

Coenzymes are small organic non-protein molecules that carry chemical groups between enzymes.[1] Coenzymes are sometimes referred to as cosubstrates. These molecules are substrates for enzymes and do not form a permanent part of the enzymes' structures. This distinguishes coenzymes from prosthetic groups, which are non-protein components that are bound tightly to enzymes - such as iron-sulfur centers, flavin or haem groups. Both coenzymes and prosthetic groups are types of the broader group of cofactors, which are any non-protein molecules (usually organic molecules or metal ions) that are required by an enzyme for its activity.[2]

In metabolism, coenzymes are involved in both group-transfer reactions, for example coenzyme A and adenosine triphosphate (ATP), and redox reactions, such as coenzyme Q10 and nicotinamide adenine dinucleotide (NAD+). Coenzymes are consumed and recycled continuously in metabolism, with one set of enzymes adding a chemical group to the coenzyme and another set removing it. For example, enzymes such as ATP synthase continuously phosphorylate adenosine diphosphate (ADP), converting it into ATP, while enzymes such as kinases dephosphorylate the ATP and convert it back to ADP.

Coenzymes molecules are often vitamins or are made from vitamins. Many conezymes contain the nucleotide adenosine as part of their structures, such as ATP, coenzyme A and NAD+. This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world.

## Coenzymes as metabolic intermediates

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Space-filling model of the coenzyme nicotinamide adenine dinucleotide.

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 NAD+ to NADH. This reduced coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.[5]

Coenzymes are therefore continuously recycled as part of metabolism. As an example, the total quantity of ATP in the human body is about 0.1 mole. This ATP is constantly being broken down into ADP, and then converted back into ATP. Thus, at any given time, the total amount of ATP + ADP remains fairly constant. The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily which is around 50 to 75 kg. Typically, a human will use up their body weight of ATP over the course of the day.[6] This means that each ATP molecule is recycled 1000 to 1500 times daily.

## Types

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Coenzymes are the major role in organisms of vitamins, although vitamins do have other functions in the body.[7] 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. Most coenzymes are found in a huge variety of species, and some are universal to all forms of life. An exception to this wide distribution is a group of unique coenzymes that evolved in methanogens, which are restricted to this group of archaea.[8]

### Vitamins and derivatives

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Coenzyme | Vitamin | Additional component | Chemical group(s) transferred | Distribution

|
|
|
|

NAD+ and NADP+ [5] | Niacin (B3) | ADP | Electrons | Bacteria, archaea and eukaryotes
Coenzyme A [9] | Pantothenic acid (B5) | ADP | Acetyl group and other acyl groups | Bacteria, archaea and eukaryotes
Tetrahydrofolic acid [10] | Folic acid (B9) | Glutamate residues | Methyl, formyl, methylene and formimino groups | Bacteria, archaea and eukaryotes
Menaquinone [11] | Vitamin K | None | Carbonyl group and electrons | Bacteria, archaea and eukaryotes
Ascorbic acid [12] | Vitamin C | None | Electrons | Bacteria, archaea and eukaryotes
Coenzyme F420 [13] | Riboflavin (B2) | Amino acids | Electrons | Methanogens and some bacteria

### Non-vitamins

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Coenzyme | Chemical group(s) transferred | Distribution

|
|

Adenosine triphosphate [14] | Phosphate group | Bacteria, archaea and eukaryotes
S-Adenosyl methionine [15] | Methyl group | Bacteria, archaea and eukaryotes
3'-Phosphoadenosine-5'-phosphosulfate [16] | Sulfate group | Bacteria, archaea and eukaryotes
Coenzyme Q [17] | Electrons | Bacteria, archaea and eukaryotes
Tetrahydrobiopterin [18] | Oxygen atom and electrons | Bacteria, archaea and eukaryotes
Cytidine triphosphate [19] | Diacylglycerols and lipid head groups | Bacteria, archaea and eukaryotes
Nucleotide sugars [20] | Monosaccharides | Bacteria, archaea and eukaryotes
Glutathione [21][22] | Electrons | Some bacteria and most eukaryotes
Coenzyme M [23][24] | Methyl group | Methanogens
Coenzyme B [25] | Electrons | Methanogens
Methanofuran [26] | Formyl group | Methanogens
Tetrahydromethanopterin [27] | Methyl group | Methanogens

## Evolution

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Further information: [[:Abiogenesis]]

Coenzymes, such as ATP and NADH, are present in all known forms of life and form a core part of metabolism. Such universal conservation indicates that these molecules evolved very early in the development of living things.[28] At least some of the current set of coenzymes may therefore have been present in the last universal ancestor, which lived about 4 billion years ago.[29][30]

Coenzymes may have been present even earlier in the history of life on Earth.[31] Interestingly, the nucleotide adenosine is present in coenzymes that catalyse many basic metabolic reactions such as methyl, acyl, and phosphoryl group transfer, as well as redox reactions. This ubiquitous chemical scaffold has therefore been proposed to be a remnant of the RNA world, with early ribozymes evolving to bind a restricted set of nucleotides and related compounds.[32][33] 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 originally evolved to bind a different cofactor.[34] This process of adapting a pre-evolved structure for a novel use is referred to as exaptation.

## History

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Further information: [[:History of biochemistry]]

The first coenzyme to be discovered was NAD+, which was identified by Arthur Harden and William Youndin 1906.[35] They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a coferment. Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin.[36] Other coenzymes were identified throughout the early 20th century, with ATP being isolated in 1929 by Karl Lohmann,[37] and coenzyme A being discovered in 1945 by Fritz Albert Lipmann.[38]

The functions of coenzymes were at first mysterious, but in 1936, Otto Heinrich Warburg identified the function of NAD+ in hydride transfer.[39] This discovery was followed in the early 1940s by the work of Herman Kalckar, who established the link between the oxidation of sugars and the generation of ATP.[40] This confirmed the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941.[41] Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NAD+ linked metabolic pathways such as the citric acid cycle and the synthesis of ATP.[42]

## See also

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* Cofactor
* Enzymes
* Adenosine triphosphate

## References

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1. ↑ de Bolster, M.W.G. (1997). "Glossary of Terms Used in Bioinorganic Chemistry: Coenzymes". International Union of Pure and Applied Chemistry. Retrieved 2007-10-30.
2. ↑ de Bolster, M.W.G. (1997). "Glossary of Terms Used in Bioinorganic Chemistry: Cofactors". International Union of Pure and Applied Chemistry. Retrieved 2007-10-30.
3. ↑ 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.
4. ↑ Wimmer M, Rose I. "Mechanisms of enzyme-catalyzed group transfer reactions". Annu Rev Biochem. 47: 1031–78. PMID 354490.
5. ↑ 5.0 5.1 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.CS1 maint: Multiple names: authors list (link)
6. ↑ Di Carlo, S. E. and Coliins, H. L. (2001) "Estimating ATP resynthesis during a marathon run: a method to introduce metabolism" Advan. Physiol. Edu. 25: 70-71.
7. ↑ Bolander FF (2006). "Vitamins: not just for enzymes". Curr Opin Investig Drugs. 7 (10): 912–5. PMID 17086936.
8. ↑ Rouvière PE, Wolfe RS (1988). "Novel biochemistry of methanogenesis". J. Biol. Chem. 263 (17): 7913–6. PMID 3131330.
9. ↑ Leonardi R, Zhang YM, Rock CO, Jackowski S (2005). "Coenzyme A: back in action". Prog. Lipid Res. 44 (2–3): 125–53. PMID 15893380.CS1 maint: Multiple names: authors list (link)
10. ↑ Donnelly JG (2001). "Folic acid". Crit Rev Clin Lab Sci. 38 (3): 183–223. PMID 11451208.
11. ↑ Søballe B, Poole RK (1999). "Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management" (PDF). Microbiology (Reading, Engl.). 145 ( Pt 8): 1817&ndash, 30. PMID 10463148.
12. ↑ Linster CL, Van Schaftingen E (2007). "Vitamin C. Biosynthesis, recycling and degradation in mammals". FEBS J. 274 (1): 1–22. PMID 17222174.
13. ↑ Mack M, Grill S (2006). "Riboflavin analogs and inhibitors of riboflavin biosynthesis". Appl. Microbiol. Biotechnol. 71 (3): 265–75. PMID 16607521.
14. ↑ Knowles JR (1980). "Enzyme-catalyzed phosphoryl transfer reactions". Annu. Rev. Biochem. 49: 877–919. PMID 6250450.
15. ↑ Chiang P, Gordon R, Tal J, Zeng G, Doctor B, Pardhasaradhi K, McCann P (1996). "S-Adenosylmethionine and methylation". FASEB J. 10 (4): 471–80. PMID 8647346.CS1 maint: Multiple names: authors list (link)
16. ↑ Negishi M, Pedersen LG, Petrotchenko E; et al. (2001). "Structure and function of sulfotransferases". Arch. Biochem. Biophys. 390 (2): 149–57. PMID 11396917.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
17. ↑ Crane FL (2001). "Biochemical functions of coenzyme Q10". Journal of the American College of Nutrition. 20 (6): 591&ndash, 8. PMID 11771674.
18. ↑ Thony B, Auerbach G, Blau N (2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions". Biochem J. 347 Pt 1: 1–16. PMID 10727395.CS1 maint: Multiple names: authors list (link)
19. ↑ Buchanan (2000). Biochemistry & molecular biology of plants (1st ed. ed.). American society of plant physiology. ISBN 0-943088-39-9. Unknown parameter `|coauthors=` ignored (help)CS1 maint: Extra text (link)
20. ↑ Ginsburg V (1978). "Comparative biochemistry of nucleotide-linked sugars". Prog. Clin. Biol. Res. 23: 595–600. PMID 351635.
21. ↑ Grill D, Tausz T, De Kok LJ (2001). Significance of glutathione in plant adaptation to the environment. Springer. ISBN 1402001789.CS1 maint: Multiple names: authors list (link)
22. ↑ Meister A, Anderson ME (1983). "Glutathione". Annu. Rev. Biochem. 52: 711–60. PMID 6137189.
23. ↑ Taylor CD, Wolfe RS (1974). "Structure and methylation of coenzyme M(HSCH2CH2SO3)". J. Biol. Chem. 249 (15): 4879–85. PMID 4367810.
24. ↑ Balch WE, Wolfe RS (1979). "Specificity and biological distribution of coenzyme M (2-mercaptoethanesulfonic acid)". J. Bacteriol. 137 (1): 256–63. PMID 104960.
25. ↑ Noll KM, Rinehart KL, Tanner RS, Wolfe RS (1986). "Structure of component B (7-mercaptoheptanoylthreonine phosphate) of the methylcoenzyme M methylreductase system of Methanobacterium thermoautotrophicum". Proc. Natl. Acad. Sci. U.S.A. 83 (12): 4238–42. PMID 3086878.CS1 maint: Multiple names: authors list (link)
26. ↑ Vorholt JA, Thauer RK (1997). "The active species of 'CO2' utilized by formylmethanofuran dehydrogenase from methanogenic Archaea". Eur. J. Biochem. 248 (3): 919–24. PMID 9342247.
27. ↑ DiMarco AA, Bobik TA, Wolfe RS (1990). "Unusual coenzymes of methanogenesis". Annu. Rev. Biochem. 59: 355–94. PMID 2115763.CS1 maint: Multiple names: authors list (link)
28. ↑ Chen X, Li N, Ellington AD (2007). "Ribozyme catalysis of metabolism in the RNA world". Chem. Biodivers. 4 (4): 633–55. PMID 17443876.CS1 maint: Multiple names: authors list (link)
29. ↑ Koch A (1998). "How did bacteria come to be?". Adv Microb Physiol. 40: 353–99. PMID 9889982.
30. ↑ Ouzounis C, Kyrpides N (1996). "The emergence of major cellular processes in evolution". FEBS Lett. 390 (2): 119–23. PMID 8706840.
31. ↑ White HB (1976). "Coenzymes as fossils of an earlier metabolic state". J. Mol. Evol. 7 (2): 101–4. PMID 1263263.
32. ↑ 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.CS1 maint: Multiple names: authors list (link)
33. ↑ Jadhav VR, Yarus M (2002). "Coenzymes as coribozymes". Biochimie. 84 (9): 877–88. PMID 12458080.
34. ↑ 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.CS1 maint: Multiple names: authors list (link)
35. ↑ Harden A, Young WJ. "The Alcoholic Ferment of Yeast-Juice" Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character Vol. 78, No. 526 (Oct., 1906), pp. 369-375
36. ↑ "Fermentation of sugars and fermentative enzymes: Nobel Lecture, May 23, 1930" (PDF). Nobel Foundation. Retrieved 2007-09-30.
37. ↑ Lohmann, K. (1929) Über die Pyrophosphatfraktion im Muskel. Naturwissenschaften 17, 624–625.
38. ↑ Lipmann F (1945). "Acetylation of sulfanilamide by liver homogenates and extracts". J. Biol. Chem. 160 (1): 173–190.
39. ↑ Warburg O, Christian W. (1936). "Pyridin, the hydrogen-transferring component of the fermentation enzymes (pyridine nucleotide)". Biochemische Zeitschrift. 287: 291.
40. ↑ Kalckar HM (1974). "Origins of the concept oxidative phosphorylation". Mol. Cell. Biochem. 5 (1–2): 55&ndash, 63. PMID 4279328.
41. ↑ Lipmann F, (1941). "Metabolic generation and utilization of phosphate bond energy". Adv Enzymol. 1: 99&ndash, 162.
42. ↑ Friedkin M, Lehninger AL. (1949). "Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen". J. Biol. Chem. 178 (2): 611&ndash, 23.

## External links

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* Examples at City University of New York
* Overview at National Institutes of Health
* Coenzymes at the US National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)

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