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.
| Study ID | ST000900 |
| Study Title | Evidence that the metabolite repair enzyme NAD(P)HX epimerase has a moonlighting function |
| Study Summary | NAD(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 |
| Department | Genome and Biomedical Sciences Facility |
| Laboratory | WCMC Metabolomics Core |
| Last Name | Fiehn |
| First Name | Oliver |
| Address | 1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616 |
| ofiehn@ucdavis.edu | |
| Phone | (530) 754-8258 |
| Submit Date | 2017-11-14 |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | GC-MS |
| Release Date | 2017-11-20 |
| Release Version | 1 |
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Factors:
Subject type: Cells; Subject species: Escherichia coli (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment* |
|---|---|---|
| SA052872 | 170123blvsa14_1 | KA pt mut |
| SA052873 | 170123blvsa06_1 | KA pt mut |
| SA052874 | 170123blvsa09_1 | KA pt mut |
| SA052875 | 170123blvsa12_1 | KA pt mut |
| SA052876 | 170123blvsa02_1 | KA pt mut |
| SA052877 | 170123blvsa15_1 | KA pt mut |
| SA052878 | 170123blvsa03_1 | wild type |
| SA052879 | 170123blvsa11_1 | wild type |
| SA052880 | 170123blvsa10_1 | wild type |
| SA052881 | 170123blvsa05_1 | wild type |
| SA052882 | 170123blvsa16_1 | wild type |
| SA052883 | 170123blvsa01_1 | wild type |
| SA052884 | 170123blvsa17_1 | yjeF KO |
| SA052885 | 170123blvsa04_1 | yjeF KO |
| SA052886 | 170123blvsa08_1 | yjeF KO |
| SA052887 | 170123blvsa07_1 | yjeF KO |
| SA052888 | 170123blvsa13_1 | yjeF KO |
| SA052889 | 170123blvsa18_1 | yjeF KO |
| Showing results 1 to 18 of 18 |
