Title: alpha-Oxidation of 3-methyl-substituted fatty acids in rat liver - Production of formic acid instead of CO2, cofactor requirements, subcellular localization and formation of a 2-hydroxy-3-methylacyl-CoA intermediate
Authors: Croes, K ×
Casteels, Minne
DeHoffmann, E
Mannaerts, Guy
Van Veldhoven, Paul P #
Issue Date: Jan-1996
Publisher: Springer verlag
Series Title: European Journal of Biochemistry vol:240 issue:3 pages:674-683
Abstract: alpha-Oxidation of 3-methyl-substituted fatty acids in rat liver was studied in intact and permeabilized rat hepatocytes, and in homogenates and subcellular fractions. The experiments revealed that the primary end product of alpha-oxidation is formic acid, which is then converted to CO2. Rates of alpha-oxidation identical to those observed in intact hepatocytes were obtained in the permeabilized hepatocytes and liver homogenates when ATP, Mg2+ and CoA, and Fe2+, 2-oxoglutarate and ascorbate wore added, suggesting that alpha-oxidation involves a fatty acid activation reaction and a dioxygenase reaction. Subcellular fractionation by differential and density gradient centrifugation demonstrated that alpha-oxidation is confined to peroxisomes, which produce formic acid that is converted to CO2, mainly in the cytosol. alpha-Oxidation in broken cell systems went hand in hand with the formation of a 2-hydroxy-3-methylacyl-CoA ester. Formation of the metabolite was strictly dependent on the presence of the above-mentioned cofactors, was confined to peroxisomes and was inhibited by fenoprofen and propyl gallate, inhibitors of alpha-oxidation in intact cells, indicating that the 2-hydroxyacyl-CoA ester is a bona fide intermediate of alpha-oxidation. Selective omission of cofactors from the reaction mixture and analysis of the incubation mixtures for 3-methyl fatty acids, 3-methyl fatty acyl-CoAs and their respective 2-hydroxy derivatives revealed that the activation reaction precedes the dioxygenase (hydroxylase) reaction.
ISSN: 0014-2956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pharmacology Section (-)
Laboratory of Lipid Biochemistry and Protein Interactions
Department of Pharmaceutical & Pharmacological Sciences - miscellaneous
× corresponding author
# (joint) last author

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