Tissue-Specific Characterization of Mitochondrial Branched-Chain Keto Acid Oxidation Using a Multiplexed Assay Platform.

Tissue-Specific Characterization of Mitochondrial Branched-Chain Keto Acid Oxidation Using a Multiplexed Assay Platform. Biochem J. 2019 May 15;: Authors: Goldberg EJ, Buddo KA, McLaughlin KL, Fernandez RF, Pereyra AS, Psaltis CE, Lin CT, Hagen JT, Boykov IN, Nguyen TK, Gowdy KM, Ellis JM, Neufer PD, McClung JM, Fisher-Wellman KH Abstract Alterations to branched chain-keto acid (BCKA) oxidation have been implicated in a wide variety of human diseases, ranging from diabetes to cancer. Although global shifts in BCKA metabolism-evident by gene transcription, metabolite profiling, and in vivo flux analyses have been documented across various pathological conditions, the underlying biochemical mechanism(s) within the mitochondrion remain largely unknown. In vitro experiments using isolated mitochondria represent a powerful biochemical tool for elucidating the role of the mitochondrion in driving disease. Such analyses have routinely been utilized across disciplines to shed valuable insight on mitochondrial-linked pathologies. That said, few studies have attempted to model in vitro BCKA oxidation in isolated organelles. The impetus for the present study stemmed from the knowledge that complete oxidation of each of the three BCKAs involves a reaction dependent upon bicarbonate and ATP, both of which are not typically included in respiration experiments.  Based on this, it was hypothesized that the inclusion of exogenous bicarbonate and sti...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research