Summary of Study ST000900

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000626. The data can be accessed directly via it's Project DOI: 10.21228/M8RH5S This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files
Study IDST000900
Study TitleEvidence that the metabolite repair enzyme NAD(P)HX epimerase has a moonlighting function
Study SummaryNAD(P)H-hydrate epimerase (EC 5.1.99.6) is known to help repair NAD(P)H hydrates (NAD(P)HX), which are damage products existing as R and S epimers. The S epimer is reconverted to NAD(P)H by a dehydratase; the epimerase facilitates epimer interconversion. Epimerase deficiency in humans causes a lethal disorder attributed to NADHX accumulation. However, bioinformatic evidence suggests caution about this attribution by predicting that the epimerase has a second function connected to vitamin B6 (pyridoxal 5'-phosphate and related compounds). Specifically, (i) the epimerase is fused to a B6 salvage enzyme in plants, (ii) epimerase genes cluster on the chromosome with B6-related genes in bacteria, and (iii) epimerase and B6-related genes are coexpressed in yeast and Arabidopsis. The predicted second function was explored in Escherichia coli, whose epimerase and dehydratase are fused and encoded by the yjeF gene. The putative NAD(P)HX epimerase active site has a conserved lysine residue (K192 in E. coli YjeF). Changing this residue to alanine cut in-vitro epimerase activity by ≥95% but did not affect dehydratase activity. Mutant cells carrying the K192A mutation had essentially normal NAD(P)HX levels, showing that the mutation had very little or no effect on NAD(P)HX repair in vivo. However, these cells showed metabolome changes, particularly in amino acids, that exceeded those in cells lacking the entire yjeF gene. The K192A mutant cells also had lower levels of free pyridoxal 5'-phosphate than wild-type cells. These results provide strong circumstantial evidence that the epimerase has a metabolic function beyond NAD(P)HX repair and that this function involves vitamin B6.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2017-11-14
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2017-11-20
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M8RH5S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Combined analysis:

Analysis ID AN001466
Analysis type MS
Chromatography type GC
Chromatography system Agilent
Column Restek Rtx-5Sil MS (30 x 0.25mm, 0.25um)
MS Type EI
MS instrument type GC Ion Trap
MS instrument name Varian 210-MS GC Ion Trap
Ion Mode POSITIVE
Units Counts

MS:

MS ID:MS001354
Analysis ID:AN001466
Instrument Name:Varian 210-MS GC Ion Trap
Instrument Type:GC Ion Trap
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250°C
Ionization Energy:70eV
Mass Accuracy:Nominal
Scan Range Moverz:85-500
Scanning Cycle:17 Hz
Scanning Range:80-500 Da
Skimmer Voltage:1850
  logo