Title | Vitamin C deficiency activates the purine nucleotide cycle in zebrafish. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Kirkwood JS, Lebold KM, Miranda CL, Wright CL, Miller GW, Tanguay RL, Barton CL, Traber MG, Stevens JF |
Journal | J Biol Chem |
Volume | 287 |
Issue | 6 |
Pagination | 3833-41 |
Date Published | 2012 Feb 03 |
ISSN | 1083-351X |
Keywords | alpha-Tocopherol, Animals, Antioxidants, Ascorbic Acid, Ascorbic Acid Deficiency, Energy Metabolism, Guinea Pigs, Humans, Purine Nucleotides, Zebrafish |
Abstract | Vitamin C (ascorbic acid, AA) is a cofactor for many important enzymatic reactions and a powerful antioxidant. AA provides protection against oxidative stress by acting as a scavenger of reactive oxygen species, either directly or indirectly by recycling of the lipid-soluble antioxidant, α-tocopherol (vitamin E). Only a few species, including humans, guinea pigs, and zebrafish, cannot synthesize AA. Using an untargeted metabolomics approach, we examined the effects of α-tocopherol and AA deficiency on the metabolic profiles of adult zebrafish. We found that AA deficiency, compared with subsequent AA repletion, led to oxidative stress (using malondialdehyde production as an index) and to major increases in the metabolites of the purine nucleotide cycle (PNC): IMP, adenylosuccinate, and AMP. The PNC acts as a temporary purine nucleotide reservoir to keep AMP levels low during times of high ATP utilization or impaired oxidative phosphorylation. The PNC promotes ATP regeneration by converting excess AMP into IMP, thereby driving forward the myokinase reaction (2ADP → AMP + ATP). On the basis of this finding, we investigated the activity of AMP deaminase, the enzyme that irreversibly deaminates AMP to form IMP. We found a 47% increase in AMP deaminase activity in the AA-deficient zebrafish, complementary to the 44-fold increase in IMP concentration. These results suggest that vitamin C is crucial for the maintenance of cellular energy metabolism. |
DOI | 10.1074/jbc.M111.316018 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 22170049 |
PubMed Central ID | PMC3281694 |
Grant List | P30ES000210 / ES / NIEHS NIH HHS / United States S10RR027878 / RR / NCRR NIH HHS / United States R01 HD062109 / HD / NICHD NIH HHS / United States R01 HL081721 / HL / NHLBI NIH HHS / United States R01HD062109 / HD / NICHD NIH HHS / United States P30 ES000210-38 / ES / NIEHS NIH HHS / United States S10 RR027878 / RR / NCRR NIH HHS / United States R01HL081721 / HL / NHLBI NIH HHS / United States P30 ES000210 / ES / NIEHS NIH HHS / United States |