Peroxisomal bifunctional enzyme (enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase) (EHHADH)

EHHADH encodes the peroxisomal bifunctional enzyme, which catalyzes two sequential steps in the β-oxidation of fatty acids within peroxisomes—the hydration of enoyl-CoA into 3-hydroxyacyl-CoA and the subsequent dehydrogenation to 3-ketoacyl-CoA. The enzyme is essential for the metabolism of straight-chain and dicarboxylic fatty acids, particularly during fasting, where it is indispensable for the production of medium-chain dicarboxylic acids (e.g., adipic and suberic acid) and their carnitine esters. EHHADH activity is highly inducible by PPARα agonists such as fibrates and is critical for energy generation from fatty acids in the liver. Genetic defects in EHHADH are implicated in peroxisomal disorders like Zellweger syndrome, and alterations in its expression or activity may influence glucose metabolism and contribute to metabolic and renal diseases. The enzyme acts as a trifunctional protein with additional isomerase activity, handling a variety of β-oxidation substrates, and participates in coordinated metabolic responses to fasting and peroxisome proliferator drugs.

Other names

Peroxisomal bifunctional enzymeEnoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase3,2-trans-enoyl-CoA isomeraseL-bifunctional proteinMultifunctional enzyme 1ECHDPBEPBFELBPMFE1FRTS3LBFPECHP

Activation by PPARα agonists, which induce enzyme expression and activity