title: Mitochondrial beta-oxidation of 2-methyl fatty acids in rat liver.
abstract: The mitochondrial beta-oxidation of 2-methyl fatty acids was studied with coupled rat liver mitochondria and purified enzymes. Measurements of mitochondrial respiration supported by 2-methyl fatty acids, straight chain fatty acids, or their coenzyme A (CoA) thioesters revealed that free short-chain and medium-chain 2-methyl fatty acids are oxidized nearly or as efficiently as are their straight chain analogs. Long-chain 2-methyl hexadecanoyl-CoA is also oxidized, although more slowly than its unbranched counterpart. However, medium-chain 2-methyldecanoyl-CoA, in contrast to its unbranched analog, is not oxidized at all. Of all acyl-CoA dehydrogenases only long-chain acyl-CoA dehydrogenase acts on medium-chain and long-chain 2-methylacyl-CoA thioesters. The resultant 2-methyl-2-enoyl-CoA thioesters are substrates of the mitochondrial trifunctional beta-oxidation complex which catalyzes the sequential hydration, dehydrogenation, and thiolytic cleavage of 2-methyl-substituted substrates to yield chain-shortened acyl-CoA thioesters and propionyl-CoA. The matrix enzymes L-3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase, in contrast to enoyl-CoA hydratase, are inactive with medium-chain and long-chain 2-methyl-substituted chain substrates. The specificity of the beta-oxidation enzymes toward 2-methyl-branched substrates forms the basis for assays of long-chain acyl-CoA dehydrogenase and the trifunctional beta-oxidation complex in the presence of their mitochondrial isozymes. It is concluded that rat liver mitochondria can oxidize 2-methyl fatty acids, but does so most effectively with medium-chain and short-chain ones that can enter mitochondria directly in a carnitine-independent manner.
authors.affiliation: Department of Chemistry, City College of the City University of New York, New York 10031, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Mao
authors.forename: C
authors.initials: C
authors.lastname: Chu
authors.forename: M J
authors.initials: MJ
authors.lastname: Luo
authors.forename: A
authors.initials: A
authors.lastname: Simon
authors.forename: A S
authors.initials: AS
authors.lastname: Abbas
authors.forename: H
authors.initials: H
authors.lastname: Schulz
mesh_terms: D000214:Acyl Coenzyme A / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005230:Fatty Acids, Nonesterified / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007202:Indicators and Reagents; D008099:Liver / Q000378:metabolism*; D008745:Methylation; D008830:Microbodies / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D007202:Indicators and Reagents; D009243:NAD