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Literature summary for 4.2.1.93 extracted from

  • Becker-Kettern, J.; Paczia, N.; Conrotte, J.F.; Zhu, C.; Fiehn, O.; Jung, P.P.; Steinmetz, L.M.; Linster, C.L.
    NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells (2018), FEBS J., 285, 3376-3401 .
    View publication on PubMed
Search for more literature for 4.2.1.93

Cloned(Commentary)

Cloned (Comment) Organism
gene NAXD, expression analysis Homo sapiens
gene YKL151C, located on chromosome 11, expression analysis Saccharomyces cerevisiae

Protein Variants

Protein Variants Comment Organism
additional information 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 Saccharomyces cerevisiae

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Saccharomyces cerevisiae 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide Homo sapiens
-
 ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide Saccharomyces cerevisiae
-
 ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide Saccharomyces cerevisiae ATCC 204508 / S288c
-
 ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate Homo sapiens
-
 ADP + phosphate + NADPH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate Saccharomyces cerevisiae
-
 ADP + phosphate + NADPH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate Saccharomyces cerevisiae ATCC 204508 / S288c
-
 ADP + phosphate + NADPH
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q8IW45
-
-
Saccharomyces cerevisiae P36059
-
-
Saccharomyces cerevisiae ATCC 204508 / S288c P36059
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
-
 Homo sapiens ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
-
 Saccharomyces cerevisiae ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
-
 Saccharomyces cerevisiae ATCC 204508 / S288c ADP + phosphate + NADH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
-
 Homo sapiens ADP + phosphate + NADPH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
-
 Saccharomyces cerevisiae ADP + phosphate + NADPH
-
 ?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
-
 Saccharomyces cerevisiae ATCC 204508 / S288c ADP + phosphate + NADPH
-
 ?

Synonyms

Synonyms Comment Organism
NAD(P)HX dehydratase
-
 Homo sapiens
NAD(P)HX dehydratase
-
 Saccharomyces cerevisiae
NAXD
-
 Homo sapiens
YKL151C
-
 Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
ATP dependent on Homo sapiens
ATP dependent on Saccharomyces cerevisiae

Expression

Organism Comment Expression
Homo sapiens construction of cells deficient in the NAD(P)HX repair enzymes using HAP1 haploid cell lines and genetical modification by the CRISPR/Cas9 technology to disrupt the human homologue of the Saccharomyces cerevisiae YKL151C gene, NAXD. In the NAXD KO cell line, the mutated NAXD gene encodes a truncated protein containing the first 126 amino acids (out of the 329 amino acids of the native mitochondrial isoform) followed by nine non-native amino acids. Phenotype, detailed overview additional information

General Information

General Information Comment Organism
malfunction human cells deficient in the NAD(P)HX dehydratase accumulate NADHX and show decreased viability. In addition, those cells consume more glucose and produce more lactate than the wild-type, potentially indicating impaired mitochondrial function. NADHX accumulation affects cellular functions causing the rapid and severe neurodegeneration leading to early death in NADHX repair-deficient children Homo sapiens
malfunction 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 Saccharomyces cerevisiae
metabolism 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 Saccharomyces cerevisiae
metabolism 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 Homo sapiens
physiological function 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 Homo sapiens
physiological function 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 Saccharomyces cerevisiae