TitleVitamin C deficiency activates the purine nucleotide cycle in zebrafish.
Publication TypeJournal Article
Year of Publication2012
AuthorsKirkwood, JS, Lebold, KM, Miranda, CL, Wright, CL, Miller, GW, Tanguay, RL, Barton, CL, Traber, MG, Stevens, JF
JournalJ Biol Chem
Volume287
Issue6
Pagination3833-41
Date Published2012 Feb 03
ISSN1083-351X
Keywordsalpha-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.

DOI10.1074/jbc.M111.316018
Alternate JournalJ. Biol. Chem.
PubMed ID22170049
PubMed Central IDPMC3281694
Grant ListP30ES000210 / 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