Human Cytochrome P450scc (CYP11A1) Catalyzes Epoxide Formation with Ergosterol

Abstract

ABSTRACT:Cytochrome P450scc (P450scc) catalyzes the cleavage of the side chain of both cholesterol and the vitamin D 3 precursor, 7-dehydrocholesterol. The aim of this study was to test the ability of human P450scc to metabolize ergosterol, the vitamin D 2 precursor, and define the structure of the major products. P450scc incorporated into the bilayer of phospholipid vesicles converted ergosterol to two major and four minor products with a k cat of 53 mol ⅐ min

Synthesis of brassinosteroids with a keto group in the side chain

“…However, this process is still poorly studied, especially with respect to metabolic transformations of the side chain. Similar 22-dehydrogenation has not been described at all so far for BS, although steroidal 23-hydroxy-22-ketones are known as natural compounds [5][6][7].…”

Lumisterol is metabolized by CYP11A1: Discovery of a new pathway

“…Bovine and human CYP11A1, human adrenodoxin and human adrenodoxin reductase were expressed in Escherichia coli and purified as described previously (Tuckey and Sadleir, 1999; Tuckey et al, 2012, Woods et al, 1998). Highly purified bovine CYP11A1 was used for small scale metabolic and kinetic studies and was prepared from adrenal mitochondria by extraction with sodium cholate, ammonium sulfate fractionation and octyl Sepharose chromatography (Tuckey and Stevenson., 1984).…”

“…We and others have also reported the presence of CYP11A1 in human skin (Slominski et al, 1996, 2004, 2014a; Thiboutot et al, 2003;) and have detected CYP11A1-dependent production of 20(OH)D3 by cultured keratinocytes in the absence of exogenous vitamin D3 substrate (Slominski et al, 2012a). These findings, together with the ability of CYP11A1 to act on 7-DHC (Slominski et al, 2004, 2009, 2012b), ergosterol (Slominski et al, 2005b; Tuckey et al, 2012) and vitamin D2 (Nguyen et al, 2009; Slominski et al, 2006, 2014b) has prompted us to test the ability of this enzyme to act on L3.…”

2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation

“…8 They are synthesized in steroidogenic tissues or organs, such as the 9 adrenal glands or the gonads, in a series of reactions involving six 10 different cytochromes P450 (CYPs) [1][2][3]. Steroid hormones are 11 categorized into three main classes: the mineralocorticoids and 12 glucocorticoids, regulating the salt and sugar homeostasis, 13 respectively, as well as the sex hormones, which are necessary 14 for the development of the secondary sexual characteristics and for 15 reproduction [2,4].…”

“…This is the first 31 enzymatic and rate-limiting step and is catalyzed by the side-chain 32 cleaving cytochrome P450CYP11A1 [10,11], a mitochondrial cyto- 33 chrome P450 found primarily in the steroidogenic cells of the 34 adrenal cortex and the gonads as well as in the skin and brain [12]. 35 The side chain cleavage of cholesterol by CYP11A1 is performed 36 through three consecutive steps: two hydroxylations at C22 and 37 C20, respectively, followed by the cleavage of the C20-C22 bond 38 [2,10,13]. The resulting product, pregnenolone, is the precursor of 39 all classes of steroid hormones: mineralocorticoids, glucocorti- 40 coids and sex hormones [14,15].…”