3-hydroxyisobutyryl-CoA hydrolase, mitochondrial (HIBCH)

3-hydroxyisobutyryl-CoA hydrolase, mitochondrial (HIBCH), is a nuclear-encoded, mitochondrial matrix enzyme that catalyzes the hydrolysis of 3-hydroxyisobutyryl-CoA to 3-hydroxyisobutyrate, a key step in the catabolic pathway of the essential branched-chain amino acid valine[1][2][3][4][6]. Deficiency of HIBCH activity impairs valine degradation, causing a buildup of toxic intermediates and severe mitochondrial dysfunction, clinically manifesting as HIBCH deficiency syndrome, a rare, inherited metabolic disorder with neurological symptoms such as developmental delay, seizures, and Leigh-like features on imaging[3][5]. HIBCH also plays a role in supporting mitochondrial energy metabolism, linking amino acid degradation to TCA cycle intermediates and oxidative phosphorylation, and is under investigation for its potential role in cancer cell metabolism[2][4].

Other names

3-hydroxyisobutyryl-CoA hydrolaseHIBCHHIB-CoA hydrolaseHIBYL-CoA-H3-hydroxyisobutyryl-coenzyme A hydrolaseHIBYLCOAHtesticular tissue protein Li 863-hydroxy-2-methylpropanoyl-CoA hydrolaseHIB CoA deacylase

Not currently targeted by medicines; hypothetical mechanisms would involve either: - Enzyme replacement/modulation to restore deficient HIBCH activity in metabolic disease - Potential metabolic pathway modulation in cancer cells by altering valine catabolism