3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP) (EBP)

3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase, commonly known as the Emopamil-binding protein (EBP), is a critical enzyme located in the endoplasmic reticulum that participates in the post-lanosterol steps of cholesterol biosynthesis [1, 2]. It catalyzes the conversion of Delta(8)-sterol intermediates, such as zymosterol, into their corresponding Delta(7)-isomers, a necessary step for the production of mature cholesterol [2, 5]. Beyond its primary enzymatic function, EBP is a key component of the microsomal antiestrogen binding site (AEBS), a protein complex that interacts with various therapeutic agents, including tamoxifen and clomiphene [1, 4]. Mutations in the EBP gene are the underlying cause of Conradi-Hünermann-Happle syndrome (CDPX2), an X-linked dominant disorder characterized by skeletal dysplasia, skin defects, and cataracts due to impaired sterol metabolism [12, 15, 16]. The enzyme also plays a role in regulating the Hedgehog signaling pathway by inhibiting the cholesterylation of the Smoothened receptor [9, 35]. Because it binds a wide variety of lipophilic amines, EBP is often an off-target for many drugs, which can lead to unintended disruptions in cholesterol synthesis and potential developmental toxicity [4, 12]. Consequently, it serves as an important focus for both metabolic research and safety pharmacology.

Other names

Sterol Delta8-Delta7-isomeraseSterol Delta7-Delta8-isomeraseCholestenol Delta-isomeraseEmopamil-binding proteinD8-D7 sterol isomeraseCholesterol-5,6-epoxide hydrolase subunit EBPCPXCDPX2CHO2

Inhibition of the sterol Delta(8)-Delta(7) isomerase enzyme activity, which blocks the conversion of Delta(8)-sterols to Delta(7)-sterols in the cholesterol biosynthetic pathway [1, 2]. It also acts as a component of the microsomal antiestrogen binding site (AEBS), where it binds ligands like tamoxifen to modulate cholesterol epoxide metabolism [1, 4].