3-hydroxyisobutyrate dehydrogenase, mitochondrial (HIBADH)

3-hydroxyisobutyrate dehydrogenase, mitochondrial (HIBADH), is a tetrameric enzyme located in the mitochondrial matrix that catalyzes the reversible NAD+-dependent oxidation of 3-hydroxyisobutyrate, an intermediate in the valine catabolic pathway, to methylmalonate semialdehyde[4][10][11]. This reaction supports the breakdown of branched-chain amino acids for cellular energy and metabolic homeostasis. HIBADH is highly specific for its substrate and exhibits high stereoselectivity in catalysis. In mammals, HIBADH is also present in spermatozoa, where it is implicated in mitochondrial function and sperm motility, potentially serving as a biomarker for sperm quality[12][13]. Mutations or deficiencies of HIBADH may disrupt normal amino acid metabolism, but there are no current therapies or drugs targeting this enzyme, nor are there recognized safety concerns associated with its function.

Other names

HIBADHNS5ATP1β-hydroxyisobutyrate dehydrogenase3-hydroxyisobutyrate dehydrogenase, mitochondrial3'-hydroxyisobutyrate dehydrogenaseepididymis secretory sperm binding proteinHibadh (mouse/rat ortholog)

Not applicable (no approved drugs or investigational agents directly target HIBADH)