Cholesterol monooxygenase

Cholesterol monooxygenase
	Crystal structure of human cytochrome P450 11A1 as a complex with cholesterol according to PDB 3n9y
Properties of human protein
Mass / length primary structure	482 amino acids
Cofactor	Heme thiolate
Identifier
Gene name	CYP11A1
External IDs	OMIM : 118485 ; UniProt : P05108 ; MGI : 88582 ;
Enzyme classification
EC, category	1.14.15.6 , monooxygenase
Response type	Two oxidations, one split
Substrate	Cholesterol + 3 • Ferredoxin (red) + 3 • O 2
Products	Pregnenolone + isocaproic acid + 3 • Ferredoxin (oxy) + 3 • H 2 O
Occurrence
Parent taxon	Vertebrates

The cholesterol side-chain cleavage enzyme (P450scc) (also: 20.22-desmolase , Cholesterindesmolase ) is the enzyme that catalyzes the conversion of cholesterol to pregnenolone catalyzed . This reaction step is essential in the biosynthesis of steroid hormones in vertebrates . In humans, the enzyme is located on the inner wall of mitochondria in the gonads , adrenal glands and in the brain . Mutations in CYP11A1 - gene can and lead to P450cc deficiency this to adrenal insufficiency.

Variants of the enzyme may be associated with an increased risk and recurrence of prostate cancer. An earlier association of variants of CYP11A1 - promoter with the appearance of polycystic ovary syndrome was not confirmed.

Catalyzed reaction

+ O ₂ ⇒ + H ₂ O

Cholesterol is converted to pregnenolone. Vitamin D3 is also accepted as a substrate, and 20 (OH) -D3 is produced as a product, which causes keratinocytes to divide.

Individual evidence

↑ UniProt P05108
↑ Kim CJ, Lin L, Huang N, et al : Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc . In: J. Clin. Endocrinol. Metab. . 93, No. 3, March 2008, pp. 696-702. doi : 10.1210 / jc.2007-2330 . PMID 18182448 . PMC 2266942 (free full text).
↑ Celhar T, Gersak K, Ovcak Z, Sedmak B, Mlinaric-Rascan I: The presence of the CYP11A1 (TTTTA) 6 allele increases the risk of biochemical relapse in organ confined and low-grade prostate cancer . In: Cancer Genet. Cytogenet. . 187, No. 1, November 2008, pp. 28-33. doi : 10.1016 / j.cancergencyto.2008.08.003 . PMID 18992638 .
↑ Gaasenbeek M, Powell BL, Sovio U, et al : Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone . In: J. Clin. Endocrinol. Metab. . 89, No. 5, May 2004, pp. 2408-13. PMID 15126571 .
↑ Tuckey RC, Li W, Zjawiony JK, et al : Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc . In: FEBS J . . 275, No. 10, May 2008, pp. 2585-96. doi : 10.1111 / j.1742-4658.2008.06406.x . PMID 18410379 .
↑ Zbytek B, Janjetovic Z, Tuckey RC, et al : 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation . In: Journal of Investigative Dermatology . 128, No. 9, September 2008, pp. 2271-80. doi : 10.1038 / jid.2008.62 . PMID 18368131 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Steroid Hormone Metabolism - Learning and Teaching Materials

Jassal / D'Eustachio / reactome.org: Oxidation of cholesterol to 22beta-hydroxycholesterol
Jassal / D'Eustachio / reactome.org: Oxidation of 22beta-hydroxycholesterol to 20alpha, 22beta-hydroxycholesterol
Jassal / D'Eustachio / reactome.org: 20alpha, 22beta-hydroxycholesterol is cleaved by CYP11A1 to yield pregnenolone and isocaproaldehyde

[1] UniProt P05108

[2] Kim CJ, Lin L, Huang N, et al : Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc . In: J. Clin. Endocrinol. Metab. . 93, No. 3, March 2008, pp. 696-702. doi : 10.1210 / jc.2007-2330 . PMID 18182448 . PMC 2266942 (free full text).

[3] Celhar T, Gersak K, Ovcak Z, Sedmak B, Mlinaric-Rascan I: The presence of the CYP11A1 (TTTTA) 6 allele increases the risk of biochemical relapse in organ confined and low-grade prostate cancer . In: Cancer Genet. Cytogenet. . 187, No. 1, November 2008, pp. 28-33. doi : 10.1016 / j.cancergencyto.2008.08.003 . PMID 18992638 .

[4] Gaasenbeek M, Powell BL, Sovio U, et al : Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone . In: J. Clin. Endocrinol. Metab. . 89, No. 5, May 2004, pp. 2408-13. PMID 15126571 .

[5] Tuckey RC, Li W, Zjawiony JK, et al : Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc . In: FEBS J . . 275, No. 10, May 2008, pp. 2585-96. doi : 10.1111 / j.1742-4658.2008.06406.x . PMID 18410379 .

[6] Zbytek B, Janjetovic Z, Tuckey RC, et al : 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation . In: Journal of Investigative Dermatology . 128, No. 9, September 2008, pp. 2271-80. doi : 10.1038 / jid.2008.62 . PMID 18368131 .