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 . 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) .
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].
no reaction occurs in absence of ATP, AMP is completely inactive, with ADP an initial lag period is observed, but the reaction then proceeds to completion, ADP appears to be active as source of ATP
NAD(P)HX dehydratase deficiency in yeast leads to an important, temperature-dependent NADHX accumulation in quiescent cells with a concomitant depletion of intracellular NAD+ and serine pools, (S)-, (R)-, and cyclic NADHX level increases in the enzyme-deficient ykl151cDELTA strain versus wild-type strain are all significant in postdiauxic phase, phenotype, detailed overview. Impact of intracellular NADHX accumulation on gene expression and amino acid levels in yeast, e.g. decreased CHA1 (a deaminase involved in serine and threonine catabolism) expression
the metabolite repair system formed by the two enzymes NAD(P)HX dehydratase and NAD(P) HX epimerase allows reconversion of both the S- and R-epimers of NADHX and NADPHX to the normal cofactors. The NAD(P)HX dehydratase and epimerase are two members of a list of enzymes that have been recognized to participate in a process called metabolite repair or metabolite proofreading and in which a panoply of protective enzymatic activities are required to prevent the accumulation of noncanonical, potentially toxic metabolites that are formed continuously via enzymatic side reactions or spontaneous chemical reactions
the NAD(P)HX repair system has a role in preserving active forms of the central cofactors NAD and NADP and/or preventing accumulation of toxic derivatives thereof. NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH cofactors, known to inhibit several dehydrogenases in vitro. NADHX potently inhibits the first step of the serine synthesis pathway in yeast. A metabolite repair system that is conserved in all domains of life and that comprises the two enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both the S- and R-epimers of NADHX and NADPHX to the normal cofactors
generation of an enzyme-deficient ykl151cDELTA mutant strain. In strains deleted for the YKL151C gene, concentrations of (S)-, (R)-, and cyclic NADHX are significantly increased. NAD(P)HX dehydratase deficiency leads to NAD(P)HX accumulation and NAD+ depletion in yeast, which is increased at higher gorwth temepratrure of 37°C compared to 25°C, no increase of the NADHX levels is observed in the wild-type cells at 37°C, phenotype, detailed overview. Analysis of significantly changed genes with most different expression levels between wild-type and ykl151cD strains
generation of an enzyme-deficient ykl151cDELTA mutant strain. In strains deleted for the YKL151C gene, concentrations of (S)-, (R)-, and cyclic NADHX are significantly increased. NAD(P)HX dehydratase deficiency leads to NAD(P)HX accumulation and NAD+ depletion in yeast, which is increased at higher gorwth temepratrure of 37°C compared to 25°C, no increase of the NADHX levels is observed in the wild-type cells at 37°C, phenotype, detailed overview. Analysis of significantly changed genes with most different expression levels between wild-type and ykl151cD strains