Biology:Cofactor (biochemistry)

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Short description: Non-protein chemical compound or metallic ion
The succinate dehydrogenase complex showing several cofactors, including flavin, iron–sulfur centers, and heme.

A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from ligands in that they often derive their function by remaining bound.

Cofactors can be classified into two types: inorganic ions and complex organic molecules called coenzymes.[1] Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here.[2][3])

Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein.[4] The second type of coenzymes are called "cosubstrates", and are transiently bound to the protein. Cosubstrates may be released from a protein at some point, and then rebind later. Both prosthetic groups and cosubstrates have the same function, which is to facilitate the reaction of enzymes and proteins. An inactive enzyme without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is called a holoenzyme.[5] (The International Union of Pure and Applied Chemistry (IUPAC) defines "coenzyme" a little differently, namely as a low-molecular-weight, non-protein organic compound that is loosely attached, participating in enzymatic reactions as a dissociable carrier of chemical groups or electrons; a prosthetic group is defined as a tightly bound, nonpolypeptide unit in a protein that is regenerated in each enzymatic turnover.[6])

Some enzymes or enzyme complexes require several cofactors. For example, the multienzyme complex pyruvate dehydrogenase[7] at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD+) and coenzyme A (CoA), and a metal ion (Mg2+).[8]

Organic cofactors are often vitamins or made from vitamins. Many contain the nucleotide adenosine monophosphate (AMP) as part of their structures, such as ATP, coenzyme A, FAD, and NAD+. This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world. It has been suggested that the AMP part of the molecule can be considered to be a kind of "handle" by which the enzyme can "grasp" the coenzyme to switch it between different catalytic centers.[9]


Cofactors can be divided into two major groups: organic cofactors, such as flavin or heme; and inorganic cofactors, such as the metal ions Mg2+, Cu+, Mn2+ and iron–sulfur clusters.

Organic cofactors are sometimes further divided into coenzymes and prosthetic groups. The term coenzyme refers specifically to enzymes and, as such, to the functional properties of a protein. On the other hand, "prosthetic group" emphasizes the nature of the binding of a cofactor to a protein (tight or covalent) and, thus, refers to a structural property. Different sources give slightly different definitions of coenzymes, cofactors, and prosthetic groups. Some consider tightly bound organic molecules as prosthetic groups and not as coenzymes, while others define all non-protein organic molecules needed for enzyme activity as coenzymes, and classify those that are tightly bound as coenzyme prosthetic groups. These terms are often used loosely.

A 1980 letter in Trends in Biochemistry Sciences noted the confusion in the literature and the essentially arbitrary distinction made between prosthetic groups and coenzymes group and proposed the following scheme. Here, cofactors were defined as an additional substance apart from protein and substrate that is required for enzyme activity and a prosthetic group as a substance that undergoes its whole catalytic cycle attached to a single enzyme molecule. However, the author could not arrive at a single all-encompassing definition of a "coenzyme" and proposed that this term be dropped from use in the literature.[10]

Inorganic cofactors

Metal ions

Metal ions are common cofactors.[11] The study of these cofactors falls under the area of bioinorganic chemistry. In nutrition, the list of essential trace elements reflects their role as cofactors. In humans this list commonly includes iron, magnesium, manganese, cobalt, copper, zinc, and molybdenum.[12] Although chromium deficiency causes impaired glucose tolerance, no human enzyme that uses this metal as a cofactor has been identified.[13][14] Iodine is also an essential trace element, but this element is used as part of the structure of thyroid hormones rather than as an enzyme cofactor.[15] Calcium is another special case, in that it is required as a component of the human diet, and it is needed for the full activity of many enzymes, such as nitric oxide synthase, protein phosphatases, and adenylate kinase, but calcium activates these enzymes in allosteric regulation, often binding to these enzymes in a complex with calmodulin.[16] Calcium is, therefore, a cell signaling molecule, and not usually considered a cofactor of the enzymes it regulates.[17]

Other organisms require additional metals as enzyme cofactors, such as vanadium in the nitrogenase of the nitrogen-fixing bacteria of the genus Azotobacter,[18] tungsten in the aldehyde ferredoxin oxidoreductase of the thermophilic archaean Pyrococcus furiosus,[19] and even cadmium in the carbonic anhydrase from the marine diatom Thalassiosira weissflogii.[20][21]

In many cases, the cofactor includes both an inorganic and organic component. One diverse set of examples is the heme proteins, which consist of a porphyrin ring coordinated to iron.[22]

Ion Examples of enzymes containing this ion
Cupric Cytochrome oxidase
Ferrous or Ferric Catalase
Cytochrome (via Heme)
Magnesium Glucose 6-phosphatase
DNA polymerase
Manganese Arginase
Molybdenum Nitrate reductase
Xanthine oxidase
Nickel Urease
Zinc Alcohol dehydrogenase
Carbonic anhydrase
DNA polymerase
A simple [Fe2S2] cluster containing two iron atoms and two sulfur atoms, coordinated by four protein cysteine residues.

Iron–sulfur clusters

Iron–sulfur clusters are complexes of iron and sulfur atoms held within proteins by cysteinyl residues. They play both structural and functional roles, including electron transfer, redox sensing, and as structural modules.[23]


Organic cofactors are small organic molecules (typically a molecular mass less than 1000 Da) that can be either loosely or tightly bound to the enzyme and directly participate in the reaction.[5][24][25][26] In the latter case, when it is difficult to remove without denaturing the enzyme, it can be called a prosthetic group. It is important to emphasize that there is no sharp division between loosely and tightly bound cofactors.[5] Indeed, many such as NAD+ can be tightly bound in some enzymes, while it is loosely bound in others.[5] Another example is thiamine pyrophosphate (TPP), which is tightly bound in transketolase or pyruvate decarboxylase, while it is less tightly bound in pyruvate dehydrogenase.[27] Other coenzymes, flavin adenine dinucleotide (FAD), biotin, and lipoamide, for instance, are tightly bound.[28] Tightly bound cofactors are, in general, regenerated during the same reaction cycle, while loosely bound cofactors can be regenerated in a subsequent reaction catalyzed by a different enzyme. In the latter case, the cofactor can also be considered a substrate or cosubstrate.

Vitamins can serve as precursors to many organic cofactors (e.g., vitamins B1, B2, B6, B12, niacin, folic acid) or as coenzymes themselves (e.g., vitamin C). However, vitamins do have other functions in the body.[29] Many organic cofactors also contain a nucleotide, such as the electron carriers NAD and FAD, and coenzyme A, which carries acyl groups. Most of these cofactors 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 cofactors that evolved in methanogens, which are restricted to this group of archaea.[30]

Vitamins and derivatives

Cofactor Vitamin Additional component Chemical group(s) transferred Distribution
Thiamine pyrophosphate[31] Thiamine (B1) pyrophosphate 2-carbon groups, α cleavage Bacteria, archaea and eukaryotes
NAD+ and NADP+[32] Niacin (B3) ADP Electrons Bacteria, archaea and eukaryotes
Pyridoxal phosphate[33] Pyridoxine (B6) None Amino and carboxyl groups Bacteria, archaea and eukaryotes
Methylcobalamin[34] Vitamin B12 Methyl group acyl groups Bacteria, archaea and eukaryotes
Cobalamine[5] Cobalamine (B12) None hydrogen, alkyl groups Bacteria, archaea and eukaryotes
Biotin[35] Biotin (H) None CO2 Bacteria, archaea and eukaryotes
Coenzyme A[36] Pantothenic acid (B5) ADP Acetyl group and other acyl groups Bacteria, archaea and eukaryotes
Tetrahydrofolic acid[37] Folic acid (B9) Glutamate residues Methyl, formyl, methylene and formimino groups Bacteria, archaea and eukaryotes
Menaquinone[38] Vitamin K None Carbonyl group and electrons Bacteria, archaea and eukaryotes
Ascorbic acid[39] Vitamin C None Electrons Bacteria, archaea and eukaryotes
Flavin mononucleotide[40] Riboflavin (B2) None Electrons Bacteria, archaea and eukaryotes
Flavin adenine dinucleotide[40] Riboflavin (B2) ADP Electrons Bacteria, archaea and eukaryotes
Coenzyme F420[41] Riboflavin (B2) Amino acids Electrons Methanogens and some bacteria


Cofactor Chemical group(s) transferred Distribution
Adenosine triphosphate[42] Phosphate group Bacteria, archaea and eukaryotes
S-Adenosyl methionine[43] Methyl group Bacteria, archaea and eukaryotes
Coenzyme B[44] Electrons Methanogens
Coenzyme M[45][46] Methyl group Methanogens
Coenzyme Q[47] Electrons Bacteria, archaea and eukaryotes
Cytidine triphosphate[48] Diacylglycerols and lipid head groups Bacteria, archaea and eukaryotes
Glutathione[49][50] Electrons Some bacteria and most eukaryotes
Heme[51] Electrons Bacteria, archaea and eukaryotes
Lipoamide[5] Electrons, acyl groups Bacteria, archaea and eukaryotes
Molybdopterin[52][53] Oxygen atoms Bacteria, archaea and eukaryotes
3'-Phosphoadenosine-5'-phosphosulfate[54] Sulfate group Bacteria, archaea and eukaryotes
Pyrroloquinoline quinone[55] Electrons Bacteria
Tetrahydrobiopterin[56] Oxygen atom and electrons Bacteria, archaea and eukaryotes
Tetrahydromethanopterin[57] Methyl group Methanogens

Cofactors as metabolic intermediates

The redox reactions of 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.[58] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions.[59] These group-transfer intermediates are the loosely bound organic cofactors, often called coenzymes.

Each class of group-transfer reaction is carried out by a particular cofactor, 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 (NAD+) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NAD+ to NADH. This reduced cofactor is then a substrate for any of the reductases in the cell that require electrons to reduce their substrates.[32]

Therefore, these cofactors are 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. In typical situations, humans use up their body weight of ATP over the course of the day.[60] This means that each ATP molecule is recycled 1000 to 1500 times daily.


Organic cofactors, 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.[61] At least some of the current set of cofactors may, therefore, have been present in the last universal ancestor, which lived about 4 billion years ago.[62][63]

Organic cofactors may have been present even earlier in the history of life on Earth.[64] The nucleotide adenosine is present in cofactors 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.[65][66] Adenosine-based cofactors are thought to have acted as interchangeable adaptors that allowed enzymes and ribozymes to bind new cofactors through small modifications in existing adenosine-binding domains, which had originally evolved to bind a different cofactor.[9] This process of adapting a pre-evolved structure for a novel use is known as exaptation.

A computational method, IPRO, recently predicted mutations that experimentally switched the cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH.[67]


The first organic cofactor to be discovered was NAD+, which was identified by Arthur Harden and William Young 1906.[68] 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.[69] Other cofactors were identified throughout the early 20th century, with ATP being isolated in 1929 by Karl Lohmann,[70] and coenzyme A being discovered in 1945 by Fritz Albert Lipmann.[71]

The functions of these molecules were at first mysterious, but, in 1936, Otto Heinrich Warburg identified the function of NAD+ in hydride transfer.[72] 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.[73] This confirmed the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941.[74] Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that NAD+ linked metabolic pathways such as the citric acid cycle and the synthesis of ATP.[75]

Protein-derived cofactors

In a number of enzymes, the moiety that acts as a cofactor is formed by post-translational modification of a part of the protein sequence. This often replaces the need for an external binding factor, such as a metal ion, for protein function. Potential modifications could be oxidation of aromatic residues, binding between residues, cleavage or ring-forming.[76] These alterations are distinct from other post-translation protein modifications, such as phosphorylation, methylation, or glycosylation in that the amino acids typically acquire new functions. This increases the functionality of the protein; unmodified amino acids are typically limited to acid-base reactions, and the alteration of resides can give the protein electrophilic sites or the ability to stabilize free radicals.[76] Examples of cofactor production include tryptophan tryptophylquinone (TTQ), derived from two tryptophan side chains,[77] and 4-methylidene-imidazole-5-one (MIO), derived from an Ala-Ser-Gly motif.[78] Characterization of protein-derived cofactors is conducted using X-ray crystallography and mass spectroscopy; structural data is necessary because sequencing does not readily identify the altered sites.

Non-enzymatic cofactors

The term is used in other areas of biology to refer more broadly to non-protein (or even protein) molecules that either activate, inhibit, or are required for the protein to function. For example, ligands such as hormones that bind to and activate receptor proteins are termed cofactors or coactivators, whereas molecules that inhibit receptor proteins are termed corepressors. One such example is the G protein-coupled receptor family of receptors, which are frequently found in sensory neurons. Ligand binding to the receptors activates the G protein, which then activates an enzyme to activate the effector.[79] In order to avoid confusion, it has been suggested that such proteins that have ligand-binding mediated activation or repression be referred to as coregulators.[80]

See also


  1. Hasim, Onn (2010). Coenzyme, Cofactor and Prosthetic Group – Ambiguous Biochemical Jargon. Kuala Lumpur: Biochemical Education. pp. 93–94. 
  2. "coenzymes and cofactors". 
  3. "Enzyme Cofactors". 
  4. Nelson, David (2008). Lehninger Principles of Biochemistry. New York: W.H. Freeman and Company. p. 184. 
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Sauke, David J.; Metzler, David E.; Metzler, Carol M. (2001). Biochemistry: the chemical reactions of living cells (2nd ed.). San Diego: Harcourt/Academic Press. ISBN 978-0-12-492540-3. 
  6. de Bolster, M. W. G. (1997). GLOSSARY OF TERMS USED IN BIOINORGANIC CHEMISTRY. Pure & Appl. Chem.. 
  7. Jordan, Frank; Patel, Mulchand S. (2004). Thiamine: catalytic mechanisms in normal and disease states. New York, N.Y: Marcel Dekker. p. 588. ISBN 978-0-8247-4062-7. 
  8. "Pyruvate Dehydrogenase Complex". Chemistry LibreTexts. 2013-10-02. 
  9. 9.0 9.1 "Adenine recognition: a motif present in ATP-, CoA-, NAD-, NADP-, and FAD-dependent proteins". Proteins 44 (3): 282–91. August 2001. doi:10.1002/prot.1093. PMID 11455601. 
  10. Bryce (March 1979). "SAM – semantics and misunderstandings". Trends Biochem. Sci. 4 (3): N62–N63. doi:10.1016/0968-0004(79)90255-X. 
  11. "Biochemistry: Enzymes: Classification and catalysis (Cofactors)". [yes|permanent dead link|dead link}}]
  12. "Physiology and metabolism of essential trace elements: an outline". Clinics in Endocrinology and Metabolism 14 (3): 513–43. August 1985. doi:10.1016/S0300-595X(85)80005-0. PMID 3905079. 
  13. "Is chromium a trace essential metal?". BioFactors 11 (3): 149–62. 2000. doi:10.1002/biof.5520110301. PMID 10875302. 
  14. "The biochemistry of chromium". The Journal of Nutrition 130 (4): 715–8. April 2000. doi:10.1093/jn/130.4.715. PMID 10736319. 
  15. "Iodine metabolism and thyroid physiology: current concepts". Thyroid 7 (2): 177–81. April 1997. doi:10.1089/thy.1997.7.177. PMID 9133680. 
  16. "Calcium signaling". Cell 131 (6): 1047–58. 2007. doi:10.1016/j.cell.2007.11.028. PMID 18083096. 
  17. "Ca2+ signaling and intracellular Ca2+ binding proteins". Journal of Biochemistry 120 (4): 685–98. October 1996. doi:10.1093/oxfordjournals.jbchem.a021466. PMID 8947828. 
  18. "The vanadium-containing nitrogenase of Azotobacter". BioFactors 1 (2): 111–6. July 1988. PMID 3076437. 
  19. "Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase". Science 267 (5203): 1463–9. March 1995. doi:10.1126/science.7878465. PMID 7878465. Bibcode1995Sci...267.1463C. 
  20. "A biological function for cadmium in marine diatoms". Proceedings of the National Academy of Sciences of the United States of America 97 (9): 4627–31. April 2000. doi:10.1073/pnas.090091397. PMID 10781068. Bibcode2000PNAS...97.4627L. 
  21. "Biochemistry: a cadmium enzyme from a marine diatom". Nature 435 (7038): 42. 2005. doi:10.1038/435042a. PMID 15875011. Bibcode2005Natur.435...42L. 
  22. "Structural analysis of heme proteins: implications for design and prediction". BMC Structural Biology 11: 13. March 2011. doi:10.1186/1472-6807-11-13. PMID 21371326. 
  23. "Iron-sulfur protein folds, iron-sulfur chemistry, and evolution". J. Biol. Inorg. Chem. 13 (2): 157–70. February 2008. doi:10.1007/s00775-007-0318-7. PMID 17992543. 
  24. Palmer, Trevor (1981). Understanding enzymes. New York: Horwood. ISBN 978-0-85312-307-1. 
  25. Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry (3rd ed.). New York: Worth Publishers. ISBN 978-1-57259-153-0. 
  26. Farrell, Shawn O.; Campbell, Mary K. (2009). Biochemistry (6th ed.). Pacific Grove: Brooks Cole. ISBN 978-0-495-39041-1. 
  27. "Studies on the nature of the binding of thiamine pyrophosphate to enzymes". The Journal of Biological Chemistry 243 (11): 3009–19. June 1968. doi:10.1016/S0021-9258(18)93372-7. PMID 4968184. 
  28. "Conservation of the Enzyme–Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme". Journal of Molecular Evolution 85 (5–6): 205–218. December 2017. doi:10.1007/s00239-017-9821-9. PMID 29177972. Bibcode2017JMolE..85..205H. 
  29. "Vitamins: not just for enzymes". Curr Opin Investig Drugs 7 (10): 912–5. 2006. PMID 17086936. 
  30. "Novel biochemistry of methanogenesis". The Journal of Biological Chemistry 263 (17): 7913–6. June 1988. doi:10.1016/S0021-9258(18)68417-0. PMID 3131330. 
  31. "Structure, mechanism and catalytic duality of thiamine-dependent enzymes". Cell. Mol. Life Sci. 64 (7–8): 892–905. 2007. doi:10.1007/s00018-007-6423-5. PMID 17429582. 
  32. 32.0 32.1 "The power to reduce: pyridine nucleotides—small molecules with a multitude of functions". Biochem. J. 402 (2): 205–18. 2007. doi:10.1042/BJ20061638. PMID 17295611. 
  33. "Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations". Annu. Rev. Biochem. 73: 383–415. 2004. doi:10.1146/annurev.biochem.73.011303.074021. PMID 15189147. 
  34. "The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes". Annu. Rev. Biochem. 72: 209–47. 2003. doi:10.1146/annurev.biochem.72.121801.161828. PMID 14527323. 
  35. "The biotin enzyme family: conserved structural motifs and domain rearrangements". Curr. Protein Pept. Sci. 4 (3): 217–29. 2003. doi:10.2174/1389203033487199. PMID 12769720. 
  36. "Coenzyme A: back in action". Prog. Lipid Res. 44 (2–3): 125–53. 2005. doi:10.1016/j.plipres.2005.04.001. PMID 15893380. 
  37. "Folic acid". Critical Reviews in Clinical Laboratory Sciences 38 (3): 183–223. June 2001. doi:10.1080/20014091084209. PMID 11451208. 
  38. "Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management". Microbiology 145 (8): 1817–30. August 1999. doi:10.1099/13500872-145-8-1817. PMID 10463148. 
  39. "Vitamin C. Biosynthesis, recycling and degradation in mammals". FEBS J. 274 (1): 1–22. 2007. doi:10.1111/j.1742-4658.2006.05607.x. PMID 17222174. 
  40. 40.0 40.1 "Flavoenzymes". Curr Opin Chem Biol 11 (2): 195–202. 2007. doi:10.1016/j.cbpa.2007.01.010. PMID 17275397. 
  41. "Riboflavin analogs and inhibitors of riboflavin biosynthesis". Appl. Microbiol. Biotechnol. 71 (3): 265–75. 2006. doi:10.1007/s00253-006-0421-7. PMID 16607521. 
  42. Bugg, Tim (1997). An introduction to enzyme and coenzyme chemistry. Oxford: Blackwell Science. pp. 95. ISBN 978-0-86542-793-8. 
  43. "S-Adenosylmethionine and methylation". FASEB Journal 10 (4): 471–80. March 1996. doi:10.1096/fasebj.10.4.8647346. PMID 8647346. 
  44. "Structure of component B (7-mercaptoheptanoylthreonine phosphate) of the methylcoenzyme M methylreductase system of Methanobacterium thermoautotrophicum". Proceedings of the National Academy of Sciences of the United States of America 83 (12): 4238–42. June 1986. doi:10.1073/pnas.83.12.4238. PMID 3086878. Bibcode1986PNAS...83.4238N. 
  45. "Structure and methylation of coenzyme M(HSCH2CH2SO3)". The Journal of Biological Chemistry 249 (15): 4879–85. August 1974. doi:10.1016/S0021-9258(19)42403-4. PMID 4367810. 
  46. "Specificity and biological distribution of coenzyme M (2-mercaptoethanesulfonic acid)". Journal of Bacteriology 137 (1): 256–63. January 1979. doi:10.1128/JB.137.1.256-263.1979. PMID 104960. 
  47. "Biochemical functions of coenzyme Q10". Journal of the American College of Nutrition 20 (6): 591–8. December 2001. doi:10.1080/07315724.2001.10719063. PMID 11771674. 
  48. Buchanan, Bob B.; Gruissem, Wilhelm; Jones, Russell L. (2000). Biochemistry & molecular biology of plants (1st ed.). American society of plant physiology. ISBN 978-0-943088-39-6. 
  49. Significance of glutathione in plant adaptation to the environment. Springer. 2001. ISBN 978-1-4020-0178-9. 
  50. "Glutathione". Annual Review of Biochemistry 52: 711–60. 1983. doi:10.1146/ PMID 6137189. 
  51. "Biology of heme in health and disease". Curr. Med. Chem. 11 (8): 981–6. 2004. doi:10.2174/0929867043455521. PMID 15078160. 
  52. "Molybdoenzymes and molybdenum cofactor in plants". Journal of Experimental Botany 53 (375): 1689–98. August 2002. doi:10.1093/jxb/erf038. PMID 12147719. 
  53. "Cell biology of molybdenum". Biochim. Biophys. Acta 1763 (7): 621–35. 2006. doi:10.1016/j.bbamcr.2006.03.013. PMID 16784786. 
  54. "Structure and function of sulfotransferases". Archives of Biochemistry and Biophysics 390 (2): 149–57. June 2001. doi:10.1006/abbi.2001.2368. PMID 11396917. 
  55. "A novel coenzyme from bacterial primary alcohol dehydrogenases". Nature 280 (5725): 843–4. August 1979. doi:10.1038/280843a0. PMID 471057. Bibcode1979Natur.280..843S. 
  56. "Tetrahydrobiopterin biosynthesis, regeneration and functions". The Biochemical Journal 347 (1): 1–16. April 2000. doi:10.1042/0264-6021:3470001. PMID 10727395. 
  57. "Unusual coenzymes of methanogenesis". Annual Review of Biochemistry 59: 355–94. 1990. doi:10.1146/ PMID 2115763. 
  58. "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". European Journal of Biochemistry 95 (1): 1–20. March 1979. doi:10.1111/j.1432-1033.1979.tb12934.x. PMID 378655. 
  59. "Mechanisms of enzyme-catalyzed group transfer reactions". Annual Review of Biochemistry 47: 1031–78. 1978. doi:10.1146/ PMID 354490. 
  60. "Estimating ATP resynthesis during a marathon run: a method to introduce metabolism". Advan. Physiol. Edu. 25 (2): 70–1. 2001. 
  61. "Ribozyme catalysis of metabolism in the RNA world". Chemistry & Biodiversity 4 (4): 633–55. 2007. doi:10.1002/cbdv.200790055. PMID 17443876. 
  62. How did bacteria come to be?. Advances in Microbial Physiology. 40. 1998. pp. 353–99. doi:10.1016/S0065-2911(08)60135-6. ISBN 9780120277407. 
  63. "The emergence of major cellular processes in evolution". FEBS Letters 390 (2): 119–23. July 1996. doi:10.1016/0014-5793(96)00631-X. PMID 8706840. 
  64. "Coenzymes as fossils of an earlier metabolic state". Journal of Molecular Evolution 7 (2): 101–4. March 1976. doi:10.1007/BF01732468. PMID 1263263. Bibcode1976JMolE...7..101W. 
  65. "The tyranny of adenosine recognition among RNA aptamers to coenzyme A". BMC Evol. Biol. 3: 26. 2003. doi:10.1186/1471-2148-3-26. PMID 14687414. 
  66. "Coenzymes as coribozymes". Biochimie 84 (9): 877–88. 2002. doi:10.1016/S0300-9084(02)01404-9. PMID 12458080. 
  67. "Computational design of Candida boidinii xylose reductase for altered cofactor specificity". Protein Science 18 (10): 2125–38. October 2009. doi:10.1002/pro.227. PMID 19693930. 
  68. "The Alcoholic Ferment of Yeast-Juice". Proceedings of the Royal Society B: Biological Sciences 78 (526): 369–75. 24 October 1906. doi:10.1098/rspb.1906.0070. 
  69. "Fermentation of sugars and fermentative enzymes: Nobel Lecture, May 23, 1930". Nobel Foundation. 
  70. Lohmann K (August 1929). "Über die Pyrophosphatfraktion im Muskel". Naturwissenschaften 17 (31): 624–5. doi:10.1007/BF01506215. Bibcode1929NW.....17..624.. 
  71. Lipmann F (1 September 1945). "Acetylation of sulfanilamide by liver homogenates and extracts". J. Biol. Chem. 160 (1): 173–90. doi:10.1016/S0021-9258(18)43110-9. 
  72. "Pyridin, the hydrogen-transferring component of the fermentation enzymes (pyridine nucleotide)". Biochemische Zeitschrift 287: E79–E88. 1936. doi:10.1002/hlca.193601901199. 
  73. "Origins of the concept oxidative phosphorylation". Molecular and Cellular Biochemistry 5 (1–2): 55–63. November 1974. doi:10.1007/BF01874172. PMID 4279328. 
  74. Lipmann F (1941). "Metabolic generation and utilization of phosphate bond energy". A Source Book in Chemistry, 1900-1950. 1. pp. 99–162. doi:10.4159/harvard.9780674366701.c141. ISBN 9780674366701. 
  75. "Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen". J. Biol. Chem. 178 (2): 611–23. 1949. doi:10.1016/S0021-9258(18)56879-4. PMID 18116985. 
  76. 76.0 76.1 "Protein-Derived Cofactors. Expanding the Scope of Post-Translational Modifications†". Biochemistry 46 (18): 5283–5292. 2007. doi:10.1021/bi700468t. PMID 17439161. 
  77. "Posttranslational biosynthesis of the protein-derived cofactor tryptophan tryptophylquinone". Annual Review of Biochemistry 82: 531–50. 2013. doi:10.1146/annurev-biochem-051110-133601. PMID 23746262. 
  78. "A new member of the 4-methylideneimidazole-5-one-containing aminomutase family from the enediyne kedarcidin biosynthetic pathway". Proceedings of the National Academy of Sciences of the United States of America 110 (20): 8069–74. May 2013. doi:10.1073/pnas.1304733110. PMID 23633564. Bibcode2013PNAS..110.8069H. 
  79. Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James (2000-01-01). "G Protein–Coupled Receptors and Their Effectors". Molecular Cell Biology (4th ed.). 
  80. "Coactivators and corepressors: what's in a name?". Molecular Endocrinology 22 (10): 2213–4. October 2008. doi:10.1210/me.2008-0201. PMID 18701638. 

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