Side chain cleavage enzyme P450scc

Testiculat androgens are synthesized in the interstitial tissue by the Leydig cells. The immediate precursor of the gonadal steroids, as for the adrenal steroids, is cholesterol. The rate-limiting step, as in the adrenal, is delivery of cholesterol to the inner membrane of the mitochondria by the transport protein StAR. Once in the proper location, cholesterol is acted upon by the side chain cleavage enzyme P450scc. The conversion of cholesterol to pregnenolone is identical in adrenal, ovary, and testis. In the latter two tissues, however, the reaction is promoted by LH rather than ACTH. 

Tee MK, Abramsohn M, Loewenthal N, Harris M, Si waeh S, Kaplinsky A, Markus B, Birk O, Sheffield VC, Parvari R, Hershkovitz E, Miller WL (2013) Varied clinieal presentations of seven patients with mutations in CYPllAl encoding the cholesterol side-chain cleavage enzyme, P450scc. J Clin Endocrinol Metab 98 713-720... 

CYPUAl P450scc Cholesterol side-chain cleavage enzyme— Pregnenolone... 

As the SCCE described above (Section 6.3.1.1) maybe part of a protein complex in the mitochondria, more effort was directed to study the possible interaction partners, especially the peripheral-t)q)e benzodiazepine receptor (PBR) (Papadopoulos et al, 1997 Koch, 2002) and the acyl-CoA-binding protein (ACBP Metzner et al, 2000). The ACBPs bind to the peripheral-t)q)e PBR present in the envelope of mitochondria (Gamier et al, 1994). This interaction stimulates the transport of cholesterol into mitochondria (Papadopoulos and Brown, 1995). The cholesterol taken up into the mitochondria is available as a substrate to the side-chain cleavage enzyme which transforms cholesterol into pregnenolone (Papadopoulos et al, 1997). Because of its interaction with PBR, ACBP is also described as diazepam-binding inhibitor or endozepine. Some isoforms of the latter were isolated and characterized from D. lanata (Metzner et al, 2000). Lindemann and Luckner (1997) speculated that cardenolide formation is regulated mainly by the availability of cholesterol and its transport into mitochondria, where the P450scc is assumed to be located. 

Enzymes of the biosynthetic pathway of steroid hormones can also be demonstrated effectively in immunohistochemical formats. Among the enzymes that have been localized are P450scc (cholesterol side chain cleavage), 3 3-hydroxysteroid dehydrogenase, 21-hydroxylase, 17a-hydroxylase, and lip-hydroxylase. " To date, however, there have been relatively few studies evaluating antibodies to these enzymes as diagnostic reagents. 

Cytochrome P450 22A1 (the trivial name of which is cytochrome P450scc) was identified in human and bovine adrenal mitochondria. This enzyme mediates the cleavage of the cholesterol side chain to pregnenolone, which is the first stage in the biosynthesis of several steroidal hormones. 

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