Characterization of a mitochondrial transport system for branched chain alpha-keto acids.
Efflux of branched chain alpha-keto acids from preloaded rat heart mitochondria was slow at low external pH. Efflux was first order, and measured rate constants, kappa efflux, were 0.104 +/- 0.005 and 0.115 +/- 0.006 min-1 for alpha-ketoisovalerate and alpha-ketoisocaproate (KIC), respectively. Efflux was stimulated significantly by branched chain alpha-keto acids and related carboxylates such as alpha-ketocaproate and alpha-ketovalerate, but not by substrates for the pyruvate transporter. KIC was the preferred substrate, and the apparent exchange K0.5 for KIC was 0.14 +/- 0.10 mM. Exchange was 7-8-fold faster than efflux, and the maximal rate of exchange at saturating concentrations of alpha-ketoisovalerate and KIC appeared to be independent of the metabolite used. It is proposed that branched chain alpha-keto acids cross the inner mitochondrial membrane on a specific transporter. Transport occurs with a proton, i.e. by proton symport, and is sensitive to inhibition by cinnamic acid derivatives.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology; D045782:Hemiterpenes; D006863:Hydrogen-Ion Concentration; D007651:Keto Acids / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D002264:Carboxylic Acids; D002352:Carrier Proteins; D003373:Coumaric Acids; D045782:Hemiterpenes; D007651:Keto Acids; D011773:Pyruvates; C018254:alpha-cyano-3-hydroxycinnamate; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid