Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) (EHHADH)

Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) is a key bifunctional enzyme located in the peroxisome, where it plays a critical role in the beta-oxidation of long-chain fatty acids and dicarboxylic acids (UniProt P07896). It possesses both hydratase and dehydrogenase activities, facilitating the conversion of enoyl-CoA intermediates into 3-ketoacyl-CoA (PubMed: 24411253). While primarily known for its metabolic function, EHHADH has gained clinical significance due to its association with Fanconi renotubular syndrome 3, where a specific missense mutation leads to mitochondrial interference and renal dysfunction (PubMed: 24411253). In the context of pharmacology, EHHADH is a well-known target gene of the peroxisome proliferator-activated receptor alpha (PPAR-alpha), and its expression is significantly induced by fibrate drugs in rodent models (PubMed: 10960473). Although not a primary target for current small-molecule inhibitors, its role in lipid metabolism and its involvement in certain cancers, such as hepatocellular carcinoma, make it a subject of interest for metabolic and oncological research (PubMed: 31513861). Understanding EHHADH is essential for managing peroxisomal disorders and exploring the systemic effects of lipid-modulating therapies. The enzyme's dual catalytic nature makes it a unique component of the peroxisomal machinery compared to the mitochondrial beta-oxidation system. Research continues to investigate how EHHADH levels correlate with metabolic health and its potential as a biomarker for renal and hepatic conditions.

Other names

L-bifunctional enzymePeroxisomal bifunctional enzymePBFEECHDFRTS3L-PBE

Induction of enzyme expression via PPAR-alpha activation; catalytic hydration of 2-trans-enoyl-CoA and subsequent oxidation of 3-hydroxyacyl-CoA.