Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.15.6

Official Name

cholesterol monooxygenase (side-chain-cleaving)

Name from literature

P450scc

Pathway from literature

steroid synthesis

Pathway from KEGG

Lipid Metabolism; C21-Steroid hormone metabolism; map00140

Organisms

Human (9606)

Genome localization

15q23-q24[1583 ],

Comments

A heme-thiolate protein. The reaction proceeds in three stages, with hydroxylation at C-20 and C-22 preceding scission of the side-chain at C-20.

Rate-limiting Description

"The first and rate-limiting step in the synthesis of all steroid hormones is the conversion of cholesterol to pregnenolone by the mitochondrial enzyme, P450scc." (10418987)

"We conclude from this study that cholesterol is near-saturating for cytochrome P450scc activity in placental mitochondria due to the P450scc displaying a low K(m) for cholesterol resulting from the low and rate-limiting concentration of AR present." (12137805)

Regulatory Information

Upstream transcription factor

2516;4088;4093;55809;1387;2033;7342

Regulatory type

Detail

transcriptional factor;"TReP-132(55809),steroidogenic factor-1(2516),CBP(1387)/p300(2033)"

"p450scc expression is regulated by TReP-132, steroidogenic factor-1 and CBP/p300" (12101186)

transcriptional factor;LBP-1b(7342)

"LBP-1b is an important SF1-independent transcriptional activator stimulating P450scc expression in human placental JEG-3 cells, whereas LBP-9 modulates the action of LBP-1b, exerting both positive and negative effects" (15471945)

interact with TF;SMAD3(4088)

"Towards a proteome-scale map of the human protein-protein interaction network." (16189514)

interact with TF;SMAD9(4093)

"Towards a proteome-scale map of the human protein-protein interaction network." (16189514)

Gene ontology

Gene ontology

GO:0031966 (C) mitochondrial membrane [P05108 ];
GO:0008386 (F) cholesterol monooxygenase (side-chain-cleav... [P05108 ];
GO:0006700 (P) C21-steroid hormone biosynthetic process [P05108 ];
GO:0008203 (P) cholesterol metabolic process [P05108 ];
GO:0020037 (F) heme binding [P05108 ];
GO:0005506 (F) iron ion binding [P05108 ];
GO:0042359 (P) vitamin D metabolic process [P05108 ];
GO:0009055 (F) electron carrier activity [P05108 ];
GO:0055114 (P) oxidation reduction [P05108 ];

Subcellular localization

Localization

mitochondrion [P05108 ];

Disease relevance

Disease

Defects in CYP11A1 are a cause of congenital lipoid adrenal hyperplasia (CLAH) [MIM:201710];
also called lipoid CAH. CLAH is the most severe form of adrenal hyperplasia. This autosomal recessive and potentially lethal condition includes the onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. CLAH is a rare disease, except in Japan and Korea where it accounts for a significant percentage of cases of congenital adrenal hyperplasia [P05108 ];

Defects in CYP11A1 are a cause of congenital adrenal insufficiency (CAI) [P05108 ];

Links

SwissProt

P05108

Entrez Gene

1583

HPRD

00326



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  Last Modified: 2009-03-24  
  Design by Zhao Min