The Enzyme Database

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EC 4.2.1.93     
Accepted name: ATP-dependent NAD(P)H-hydrate dehydratase
Reaction: (1) ATP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = ADP + phosphate + NADH
(2) ATP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = ADP + phosphate + NADPH
For diagram of reaction, click here
Glossary: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = (S)-NADH-hydrate = (S)-NADHX
(6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = (S)-NADPH-hydrate = (S)-NADPHX
Other name(s): reduced nicotinamide adenine dinucleotide hydrate dehydratase; ATP-dependent H4NAD(P)+OH dehydratase; (6S)-β-6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase(ATP-hydrolysing); (6S)-6-β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ATP-hydrolysing; NADH-forming)
Systematic name: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ATP-hydrolysing; NADH-forming)
Comments: Acts equally well on hydrated NADH and hydrated NADPH. NAD(P)H spontaneously hydrates to both the (6S)- and (6R)- isomers, and these are interconverted by EC 5.1.99.6, NAD(P)H-hydrate epimerase, to a 60:40 ratio [4]. Hence EC 4.2.1.93 together with EC 5.1.99.6 can restore the mixture of hydrates into NAD(P)H [3,4]. The enzyme from eukaryotes has no activity with ADP, contrary to the enzyme from bacteria (cf. EC 4.2.1.136, ADP-dependent NAD(P)H-hydrate dehydratase) [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 116669-08-0
References:
1.  Meinhart, J.O., Chaykin, S. and Krebs, E.G. Enzymatic conversion of a reduced diphosphopyridine nucleotide derivative to reduced diphosphopyridine nucleotide. J. Biol. Chem. 220 (1956) 821–829. [PMID: 13331940]
2.  Regueiro Varela, B., Amelunxen, R. and Grisolia, S. Synthesis and degradation of monohydroxytetrahydronicotinamide adenine dinucleotide phosphate. Physiol. Chem. Phys. 2 (1970) 445–454.
3.  Acheson, S.A., Kirkman, H.N. and Wolfenden, R. Equilibrium of 5,6-hydration of NADH and mechanism of ATP-dependent dehydration. Biochemistry 27 (1988) 7371–7375. [PMID: 3061454]
4.  Marbaix, A.Y., Noel, G., Detroux, A.M., Vertommen, D., Van Schaftingen, E. and Linster, C.L. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J. Biol. Chem. 286 (2011) 41246–41252. [DOI] [PMID: 21994945]
[EC 4.2.1.93 created 1992, modified 2012]
 
 
EC 4.2.1.136     
Accepted name: ADP-dependent NAD(P)H-hydrate dehydratase
Reaction: (1) ADP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = AMP + phosphate + NADH
(2) ADP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = AMP + phosphate + NADPH
Glossary: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = (S)-NADH-hydrate = (S)-NADHX
(6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = (S)-NADPH-hydrate = (S)-NADPHX
Other name(s): (6S)-β-6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase(ADP-hydrolysing); (6S)-6-β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ADP-hydrolysing; NADH-forming)
Systematic name: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ADP-hydrolysing; NADH-forming)
Comments: Acts equally well on hydrated NADH and hydrated NADPH. NAD(P)H spontaneously hydrates to both the (6S)- and (6R)- isomers. The enzyme from bacteria consists of two domains, one of which acts as an NAD(P)H-hydrate epimerase that interconverts the two isomers to a 60:40 ratio (cf. EC 5.1.99.6), while the other catalyses the dehydration. Hence the enzyme can restore the complete mixture of isomers into NAD(P)H. The enzyme has no activity with ATP, contrary to the enzyme from eukaryotes (cf. EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Marbaix, A.Y., Noel, G., Detroux, A.M., Vertommen, D., Van Schaftingen, E. and Linster, C.L. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J. Biol. Chem. 286 (2011) 41246–41252. [DOI] [PMID: 21994945]
[EC 4.2.1.136 created 2012]
 
 
EC 5.1.99.6     
Accepted name: NAD(P)H-hydrate epimerase
Reaction: (1) (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
(2) (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
Glossary: 6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = NADHX = NADH-hydrate
6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = NADPHX = NADPH-hydrate
Other name(s): NAD(P)HX epimerase
Systematic name: (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide 6-epimerase
Comments: The enzyme can use either (R)-NADH-hydrate or (R)-NADPH-hydrate as a substrate. Its physiological role is to convert the (R) forms to the (S) forms, which could then be restored to active dinucleotides by EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Marbaix, A.Y., Noel, G., Detroux, A.M., Vertommen, D., Van Schaftingen, E. and Linster, C.L. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J. Biol. Chem. 286 (2011) 41246–41252. [DOI] [PMID: 21994945]
[EC 5.1.99.6 created 2012]
 
 


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