This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Generation of Precursor Metabolites and Energy|
Studies in the 1950's have shown that glyceraldehyde 3-phosphate dehydrogenase slowly catalyzes the formation of a hydrated form of NADH, called NADHX, from NADH [Rafter54]. The equilibrium of this hydration reaction is in favor (100/1) of the hydrated form [Acheson88], making the reaction virtually irreversible. In addition, NADHX can be formed spontaneously from NADH under slightly acidic conditions.
NADHX and NADPHX are inhibitors of several dehydrogenases [Prabhakar98] and it is thus important to eliminate them. This is achieved by the enzyme ATP-dependent NAD(P)H-hydrate dehydratase which has been originally described from yeast [Meinhart56]. Upon identification of the yeast enzyme it was found that homologs are found in the overwhelming majority of eukaryotes and prokaryotes. The human and yeast enzymes also accept (S)-NADPHX, with higher maximal activity [Marbaix11].
Since both (R)-NADHX and (S)-NADHX are formed, but ATP-dependent NAD(P)H-hydrate dehydratase can only accept the S-form, the R form needs to be epimerized to the S-form before it can converted back to NADH. This is achieved by the enzyme NADHX epimerase [Marbaix11].
While the two enzymes are encoded by two different genes in yeast and humans, in Escherichia coli a single bifunctional protein (encoded by the YjeF gene) is responsible for catalyzing both reactions. However, that protein differs from the eukaryotic proteins by using ADP rather than ATP to drive the dehydration reaction [Marbaix11].
Marbaix11: Marbaix AY, Noel G, Detroux AM, Vertommen D, Van Schaftingen E, Linster CL (2011). "Extremely Conserved ATP- or ADP-dependent Enzymatic System for Nicotinamide Nucleotide Repair." J Biol Chem 286(48);41246-52. PMID: 21994945
Meinhart56: Meinhart, J. O., Chaykin, S., Krebs, E. G. (1956). "Enzymatic conversion of a reduced diphosphopyridine nucleotide derivative to reduced diphosphopyridine nucleotide." J. Biol. Chem. 220: 821-829.
Prabhakar98: Prabhakar P, Laboy JI, Wang J, Budker T, Din ZZ, Chobanian M, Fahien LA (1998). "Effect of NADH-X on cytosolic glycerol-3-phosphate dehydrogenase." Arch Biochem Biophys 360(2);195-205. PMID: 9851831
Rafter54: Rafter, G. W., Chaykin, S., Krebs, E. G. (1954). "The action of glyceraldehyde-3-phosphate dehydrogenase on reduced diphosphopyridine nucleotide." J. Biol. Chem. 208: 799-812. PMID: 13174589
Arcari84: Arcari P, Martinelli R, Salvatore F (1984). "The complete sequence of a full length cDNA for human liver glyceraldehyde-3-phosphate dehydrogenase: evidence for multiple mRNA species." Nucleic Acids Res 12(23);9179-89. PMID: 6096821
Butterfield10: Butterfield DA, Hardas SS, Lange ML (2010). "Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration." J Alzheimers Dis 20(2);369-93. PMID: 20164570
Ercolani88: Ercolani L, Florence B, Denaro M, Alexander M (1988). "Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene." J Biol Chem 263(30);15335-41. PMID: 3170585
Hanauer84: Hanauer A, Mandel JL (1984). "The glyceraldehyde 3 phosphate dehydrogenase gene family: structure of a human cDNA and of an X chromosome linked pseudogene; amazing complexity of the gene family in mouse." EMBO J 3(11);2627-33. PMID: 6096136
Mazzola02: Mazzola JL, Sirover MA (2002). "Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders?." Neurotoxicology 23(4-5);603-9. PMID: 12428732
Piechaczyk: Piechaczyk M, Blanchard JM, Riaad-El Sabouty S, Dani C, Marty L, Jeanteur P (1984). "Unusual abundance of vertebrate 3-phosphate dehydrogenase pseudogenes." Nature 312(5993);469-71. PMID: 6095107
Tso85: Tso JY, Sun XH, Kao TH, Reece KS, Wu R (1985). "Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene." Nucleic Acids Res 13(7);2485-502. PMID: 2987855
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