title: Incomplete fatty acid oxidation. The production and epimerization of 3-hydroxy fatty acids.
abstract: 3-Hydroxydicarboxylic acids are major urinary metabolites derived from fatty acid metabolism. These compounds are produced from the omega-oxidation of 3-hydroxy fatty acids. The production of the precursor 3-hydroxy fatty acids from incomplete beta-oxidation of fatty acids in rat liver mitochondria was investigated. Independent of the chain length or the concentration of fatty acid substrates, the accumulation of 3-hydroxyacyl intermediates was relatively constant at the concentration of 3-5 nmol/mg of mitochondrial protein. The extent of the incomplete oxidation was the same in Percoll gradient-purified mitochondria. Rotenone treatment increased the production of 3-hydroxy fatty acids. 3-Hydroxy fatty acids did not exist as pure L-enantiomer as expected from beta-oxidation. Instead, these metabolites were epimerized to a near racemic mixture of D- and L-isomers with a slightly dominant D-isomer (58 +/- 3%). By using deuterium-isotope labeling, the mechanism of epimerizartion was shown to be a rapid dehydration-rehydration through trans-2-enoyl-CoA. In addition, cis-3 and trans-3 fatty acids were produced; these metabolites were derived from the isomerization of trans-2-enoyl-CoA. Epimerase and isomerase were thought to be enzymes involved in the oxidation of unsaturated fatty acids. Current data have shown that the metabolism of these acids is actually through NADPH-dependent reduction pathways. The activities of epimerase and isomerase detected in rat liver mitochondria possibly function mainly in the metabolism of saturated fatty acids in a reverse role to the conventional concept.
authors.affiliation: Medical Research Service, Veterans Affairs Medical Center, Cleveland, Ohio, 44106.
authors.forename: S J
authors.initials: SJ
authors.lastname: Jin
authors.forename: C L
authors.initials: CL
authors.lastname: Hoppel
authors.forename: K Y
authors.initials: KY
authors.lastname: Tserng
mesh_terms: D000818:Animals; D002849:Chromatography, Gas; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D007554:Isotopes; D007850:Lauric Acids / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D005227:Fatty Acids; D007554:Isotopes; D007850:Lauric Acids; D009227:Myristic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D019814:Myristic Acid; C030358:lauric acid; D019301:Oleic Acid; D019308:Palmitic Acid