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Information on EC 4.2.1.93 - ATP-dependent NAD(P)H-hydrate dehydratase and Organism(s) Homo sapiens and UniProt Accession Q8IW45

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EC Tree
     4 Lyases
         4.2 Carbon-oxygen lyases
             4.2.1 Hydro-lyases
                4.2.1.93 ATP-dependent NAD(P)H-hydrate dehydratase
IUBMB 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 . 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) .
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Homo sapiens
UNIPROT: Q8IW45
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Word Map
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  • 4.2.1.93
  • nadphx
  • epimerase
  • dehydrogenases
  • febrile
  • salvage
  • neurometabolic
  • epimer
  • neurodevelopmental
  • neurodegeneration
  • protein-truncating
  • reconvert
  • apolipoprotein
  • 5'-phosphate
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
nad(p)hx dehydratase, ykl151c, carkd, atp-dependent nnrd, atp-dependent nad(p)h-hydrate dehydratase, adp/atp-dependent nad(p)h-hydrate dehydratase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NAD(P)HX dehydratase
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ATP-dependent H4NAD(P)OH dehydratase
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-
-
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reduced nicotinamide adenine dinucleotide hydrate dehydratase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C-O bond cleavage by elimination of water
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-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ATP-hydrolysing; NADH-forming)
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].
CAS REGISTRY NUMBER
COMMENTARY hide
116669-08-0
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
ADP + phosphate + NADH
show the reaction diagram
-
-
-
?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
ADP + phosphate + NADPH
show the reaction diagram
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-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
ADP + phosphate + NADH
show the reaction diagram
-
-
-
?
ATP + (6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
ADP + phosphate + NADPH
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
dependent on
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NNRD_HUMAN
347
1
36576
Swiss-Prot
Secretory Pathway (Reliability: 1)
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NAXD, expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
FEBS J.
285
3376-3401
2018
Homo sapiens (Q8IW45), Homo sapiens, Saccharomyces cerevisiae (P36059), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 / S288c (P36059)
Manually annotated by BRENDA team