Phytanic acid must be activated to phytanoyl-CoA prior to its α-oxidation in rat liver peroxisomes

Paul A. Watkins, Annette E. Howard, Stephanie J. Mihalik

Research output: Contribution to journalArticle

Abstract

α-Oxidation of the branched-chain fatty acid, phytanic acid, is defective in patients with Refsum's disease, the disorders of peroxisome biogenesis (e.g., Zeilweger syndrome), and in rhizomelic chondrodysplasia punctata. 3H-Release from [2,3-3H]phytanic acid, which is impaired in cultured skin fibroblasts from these patients, was investigated in rat liver peroxisomes. Cofactors necessary for optimal 3H-release, ATP, Mg2+, and coenzyme A, were also necessary for optimal acyl-CoA synthetase activity, suggesting that the substrate for 3H-release might be phytanoyl-CoA. 5,8,11,14-Eicosatetraynoic acid (ETYA), an inhibitor of long-chain acyl-CoA synthetase activity, blocked phytanoyl-CoA synthesis as well as H-release from [2,3-3H]phytanic acid in a dose-dependent manner. However, this inhibitor had little effect on H-release from [2,3-3H]phytanoyl-CoA. Tetradecylglycidic acid (TDGA) inhibited 3H-release from [2,3-3H]phytanic acid in peroxisomal but not in mitochondrial fractions from rat liver. This agent inhibited 3H-release from [2,3-3H]phytanic acid and [2,3-33H]phytanoyl-CoA equally. In contrast to ETYA, which appeared to decrease 3H-release as a consequence of synthetase inhibition, TDGA appeared to act directly on the enzyme catalyzing 3H-release. This enzyme was partially purified from rat liver. The purified enzyme, which did not possess phytanoyl-CoA synthetase activity, catalyzed tritium release from [2,3-3H]phytanoyl-CoA. This enzyme catalyzed 3H-release from [2,3-3H]phytanic acid only if a source of phytanoyl-CoA synthetase was present. We conclude that in rat liver peroxisomes, phytanic acid must be activated to its coenzyme A derivative prior to subsequent α-oxidation.

Original languageEnglish (US)
Pages (from-to)288-294
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1214
Issue number3
DOIs
StatePublished - Oct 6 1994

Keywords

  • Acyl-CoA synthetase
  • Peroxisome
  • Phytanic acid
  • Refsum's disease
  • α-Oxidation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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