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Hepatic alpha-oxidation of phytanic acid. A revised pathway.
Adv Exp Med Biol. 1999; 466:273-81.AE

Abstract

Synthetic 3-methyl-branched chain fatty acids were used to decipher the breakdown of phytanic acid. Based on results obtained in intact or permeabilized rat hepatocytes, rat liver homogenates or subcellular fractions, a revised alpha-oxidation pathway is proposed which appears to be functioning in man as well. In a first step, the 3-methyl-branched chain fatty acid is activated by an acyl-CoA synthetase. This reaction requires CoA, ATP and Mg2+. Subsequently, the acyl-CoA ester is hydroxylated at position 2 by a peroxisomal dioxygenase. This step is dependent on alpha-oxoglutarate, ascorbate (or glutathione), Fe2+ and O2. The 2-hydroxy-3-methylacyl-CoA intermediate is cleaved by a peroxisomal lyase to formyl-CoA and a 2-methyl-branched fatty aldehyde. Formyl-CoA is (partly enzymically) hydrolyzed to formate, which is then converted, most likely in the cytosol, to CO2. In the presence of NAD+, the aldehyde is dehydrogenated to a 2-methyl-branched fatty acid, presumably by a peroxisomal aldehyde dehydrogenase. This acid can--after activation--be degraded via a D-specific peroxisomal beta-oxidation system.

Authors+Show Affiliations

Katholieke Universiteit Leuven, Afdeling Farmakologie Herestraat, Belgium. Paul.VanVeldhoven@med.kuleuven.ac.beNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10709654

Citation

Van Veldhoven, P P., et al. "Hepatic Alpha-oxidation of Phytanic Acid. a Revised Pathway." Advances in Experimental Medicine and Biology, vol. 466, 1999, pp. 273-81.
Van Veldhoven PP, Mannaerts GP, Casteels M, et al. Hepatic alpha-oxidation of phytanic acid. A revised pathway. Adv Exp Med Biol. 1999;466:273-81.
Van Veldhoven, P. P., Mannaerts, G. P., Casteels, M., & Croes, K. (1999). Hepatic alpha-oxidation of phytanic acid. A revised pathway. Advances in Experimental Medicine and Biology, 466, 273-81.
Van Veldhoven PP, et al. Hepatic Alpha-oxidation of Phytanic Acid. a Revised Pathway. Adv Exp Med Biol. 1999;466:273-81. PubMed PMID: 10709654.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic alpha-oxidation of phytanic acid. A revised pathway. AU - Van Veldhoven,P P, AU - Mannaerts,G P, AU - Casteels,M, AU - Croes,K, PY - 2000/3/10/pubmed PY - 2000/4/15/medline PY - 2000/3/10/entrez SP - 273 EP - 81 JF - Advances in experimental medicine and biology JO - Adv Exp Med Biol VL - 466 N2 - Synthetic 3-methyl-branched chain fatty acids were used to decipher the breakdown of phytanic acid. Based on results obtained in intact or permeabilized rat hepatocytes, rat liver homogenates or subcellular fractions, a revised alpha-oxidation pathway is proposed which appears to be functioning in man as well. In a first step, the 3-methyl-branched chain fatty acid is activated by an acyl-CoA synthetase. This reaction requires CoA, ATP and Mg2+. Subsequently, the acyl-CoA ester is hydroxylated at position 2 by a peroxisomal dioxygenase. This step is dependent on alpha-oxoglutarate, ascorbate (or glutathione), Fe2+ and O2. The 2-hydroxy-3-methylacyl-CoA intermediate is cleaved by a peroxisomal lyase to formyl-CoA and a 2-methyl-branched fatty aldehyde. Formyl-CoA is (partly enzymically) hydrolyzed to formate, which is then converted, most likely in the cytosol, to CO2. In the presence of NAD+, the aldehyde is dehydrogenated to a 2-methyl-branched fatty acid, presumably by a peroxisomal aldehyde dehydrogenase. This acid can--after activation--be degraded via a D-specific peroxisomal beta-oxidation system. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/10709654/Hepatic_alpha_oxidation_of_phytanic_acid__A_revised_pathway_ DB - PRIME DP - Unbound Medicine ER -