ZFIN ID: ZDB-PUB-120105-45
Vitamin C deficiency activates the purine nucleotide cycle in zebrafish
Kirkwood, J.S., Lebold, K.M., Miranda, C.L., Wright, C.L., Miller, G.W., Tanguay, R.L., Barton, C.L., Traber, M.G., and Stevens, J.F.
Date: 2012
Source: The Journal of biological chemistry 287(6): 3833-3841 (Journal)
Registered Authors: Tanguay, Robert L.
Keywords: mass spectrometry (MS), metabolism, metabolomics, purine, vitamin c, zebrafish
MeSH Terms:
  • Animals
  • Antioxidants/pharmacology*
  • Ascorbic Acid/pharmacology
  • Ascorbic Acid Deficiency/metabolism*
  • Energy Metabolism/drug effects*
  • Guinea Pigs
  • Humans
  • Purine Nucleotides/metabolism*
  • Zebrafish/metabolism*
  • alpha-Tocopherol/pharmacology*
PubMed: 22170049 Full text @ J. Biol. Chem.

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 (ROS), either directly or indirectly by recycling of the lipid-soluble antioxidant, α-tocopherol (α-T; vitamin E). Only a few species, including humans, guinea pigs, and zebrafish, can not synthesize AA. Using an untargeted metabolomics approach, we examined the effects of α-T 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 PN 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). Based on this finding, we investigated the activity of AMP deaminase (AMPD), the enzyme that irreversibly deaminates AMP to form IMP. We found a 47% increase in AMPD 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.