title: Oxidation of 2-oxoisocaproate and 2-oxoisovalerate by the perfused rat heart. Interactions with fatty acid oxidation.
abstract: The interactions between fatty acid oxidation and the oxidation of the 2-oxo acids of the branched chain amino acids were studied in the isolated Langendorff-perfused heart. 2-Oxoisocaproate inhibited the oxidation of oleate, but 2-oxoisovalerate and 2-oxo-3-methylvalerate did not. This difference was not attributable to the magnitude of the flux through the branched chain 2-oxo acid dehydrogenase, which was slightly higher with 2-oxoisovalerate than with 2-oxoisocaproate. Oxidation of 2-oxoisocaproate in the perfused heart was virtually complete, since more than 80% of the isovaleryl-CoA formed from 2-oxo[1-14C]isocaproate was further metabolized to CO2, as determined by comparing 14CO2 production from 2-oxo[14C(U)]isocaproate with that from the 1-14C-labelled compound. Only twice as much 14CO2 was produced from 2-oxo[14C(U)]isovalerate as from the 1-14C-labelled compound, indicating incomplete oxidation. This was confirmed by the accumulation in the perfusion medium of substantial quantities of labelled 3-hydroxyisobutyrate (an intermediate in the pathway of valine catabolism), when hearts were perfused with 2-oxo[14C(U)]isovalerate. The failure of 2-oxoisovalerate to inhibit fatty acid oxidation, then, can be attributed to the fact that its partial metabolism in the heart produces little ATP. We have previously shown that 3-hydroxyisobutyrate is a good gluconeogenic substrate in liver and kidney, and postulate that 3-hydroxyisobutyrate serves as an interorgan metabolite such that valine can serve as a glucogenic amino acid, even when its catabolism proceeds beyond the irreversible 2-oxo acid dehydrogenase in muscle.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Letto
authors.forename: J T
authors.initials: JT
authors.lastname: Brosnan
authors.forename: M E
authors.initials: ME
authors.lastname: Brosnan
mesh_terms: D000818:Animals; D002208:Caproates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D045782:Hemiterpenes; D007651:Keto Acids / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014631:Valerates / Q000378:metabolism*
chemical_list: D002208:Caproates; D005227:Fatty Acids; D045782:Hemiterpenes; D007651:Keto Acids; D009829:Oleic Acids; D014631:Valerates; D002245:Carbon Dioxide; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid