Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.

ABSTRACT: Branched-chain amino acid (BCAA) oxidation is a multistep process leading to the formation of acetyl-CoA and propionyl-CoA. The syndromes associated with disturbed BCAA oxidation are clinically and biochemically heterogenous. While the common organic acidemias, propionic (PA) and methylmalonic acidemia (MMA), arise from deficient activity of propionyl-CoA carboxylase and methylmalonyl-CoA mutase and are life-threatening conditions with limited treatment options, isobutyryl-CoA dehydrogenase (IBD), and 2-methylbutyryl-CoA dehydrogenase (2-MBD) deficiencies manifest as biochemical traits, with no associated symptoms or consistent metabolic phenotypes. To assess whether the proximal interruption of valine and isoleucine oxidation might represent an approach to treat MMA and PA, we investigate

SUBMITTER: Hong S 

PROVIDER: S-EPMC12371525 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature