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Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes.
Biochim Biophys Acta. 1994 Oct 06; 1214(3):288-94.BB

Abstract

alpha-Oxidation of the branched-chain fatty acid, phytanic acid, is defective in patients with Refsum's disease, the disorders of peroxisome biogenesis (e.g., Zellweger 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 3H-release from [2,3-3H]phytanic acid in a dose-dependent manner. However, this inhibitor had little effect on 3H-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 [2,3-3H]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 alpha-oxidation.

Authors+Show Affiliations

Kennedy Krieger Research Institute, Baltimore, MD 21205.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7918611

Citation

Watkins, P A., et al. "Phytanic Acid Must Be Activated to phytanoyl-CoA Prior to Its Alpha-oxidation in Rat Liver Peroxisomes." Biochimica Et Biophysica Acta, vol. 1214, no. 3, 1994, pp. 288-94.
Watkins PA, Howard AE, Mihalik SJ. Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. Biochim Biophys Acta. 1994;1214(3):288-94.
Watkins, P. A., Howard, A. E., & Mihalik, S. J. (1994). Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. Biochimica Et Biophysica Acta, 1214(3), 288-94.
Watkins PA, Howard AE, Mihalik SJ. Phytanic Acid Must Be Activated to phytanoyl-CoA Prior to Its Alpha-oxidation in Rat Liver Peroxisomes. Biochim Biophys Acta. 1994 Oct 6;1214(3):288-94. PubMed PMID: 7918611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. AU - Watkins,P A, AU - Howard,A E, AU - Mihalik,S J, PY - 1994/10/6/pubmed PY - 1994/10/6/medline PY - 1994/10/6/entrez SP - 288 EP - 94 JF - Biochimica et biophysica acta JO - Biochim Biophys Acta VL - 1214 IS - 3 N2 - alpha-Oxidation of the branched-chain fatty acid, phytanic acid, is defective in patients with Refsum's disease, the disorders of peroxisome biogenesis (e.g., Zellweger 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 3H-release from [2,3-3H]phytanic acid in a dose-dependent manner. However, this inhibitor had little effect on 3H-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 [2,3-3H]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 alpha-oxidation. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/7918611/Phytanic_acid_must_be_activated_to_phytanoyl_CoA_prior_to_its_alpha_oxidation_in_rat_liver_peroxisomes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0005-2760(94)90075-2 DB - PRIME DP - Unbound Medicine ER -