Beta-hydroxyisobutyryl-CoA hydrolase (HIBCH)

Beta-hydroxyisobutyryl-CoA hydrolase (HIBCH) is a mitochondrial enzyme that plays a critical role in the catabolism of the branched-chain amino acid valine. It specifically catalyzes the hydrolysis of 3-hydroxyisobutyryl-CoA into 3-hydroxyisobutyrate and free coenzyme A (UniProt P31939). This step is essential to prevent the accumulation of methacrylyl-CoA, a highly reactive and toxic intermediate that can form adducts with cysteamine and glutathione, leading to cellular damage (NCBI Gene ID: 26296). Deficiencies in HIBCH lead to a rare metabolic disorder characterized by neurodegeneration, Leigh-like syndrome, and developmental delay due to mitochondrial dysfunction and secondary respiratory chain deficiencies (OMIM: 610690). Beyond its role in metabolic disease, emerging evidence suggests that HIBCH is upregulated in various malignancies, such as colorectal and prostate cancer, where it supports increased metabolic demands for cell proliferation (PubMed: 30265317). While there are currently no approved drugs that target HIBCH, it is considered a potential metabolic vulnerability in oncology and a candidate for gene replacement therapies in the context of inherited deficiency.

Other names

3-hydroxyisobutyryl-CoA hydrolaseHIBYL-CoA hydrolase3-hydroxyisobutyryl-coenzyme A hydrolase

Hydrolysis of 3-hydroxyisobutyryl-CoA to 3-hydroxyisobutyrate and coenzyme A