The Effect of 2-Ketobutyrate on Mitochondrial Substrate-Level Phosphorylation.

The Effect of 2-Ketobutyrate on Mitochondrial Substrate-Level Phosphorylation. Neurochem Res. 2019 Feb 27;: Authors: Bui D, Ravasz D, Chinopoulos C Abstract The reaction catalyzed by succinate-CoA ligase in the mitochondrial matrix yields a high-energy phosphate when operating towards hydrolysis of the thioester bond of succinyl-CoA, known as mitochondrial substrate-level phosphorylation (mSLP). The catabolism of several metabolites converge to succinyl-CoA but through different biochemical pathways. Among them, threonine, serine and methionine catabolize to succinyl-CoA through the common intermediate, 2-ketobutyrate. During the course of this pathway 2-ketobutyrate will become succinyl-CoA through propionyl-CoA catabolism, obligatorily passing through an ATP-consuming step substantiated by propionyl-CoA carboxylase. Here, by recording the directionality of the adenine nucleotide translocase while measuring membrane potential we tested the hypothesis that catabolism of 2-ketobutyrate negates mSLP due to the ATP-consuming propionyl-CoA carboxylase step in rotenone-treated, isolated mouse liver and brain mitochondria. 2-Ketobutyrate produced a less negative membrane potential compared to NADH or FADH2-linked substrates, which was sensitive to inhibition by rotenone, atpenin and arsenate, implying the involvement of complex I, complex II and a dehydrogenase-most likely branched chain keto-acid dehydrogenase, respectively. Co-addition o...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research