CYP11A1
Function
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783).
Involvement in disease
Adrenal insufficiency, congenital, with 46,XY sex reversal
AICSR
A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Lipid metabolism; C21-steroid hormone metabolism.
Steroid metabolism; cholesterol metabolism.
Sequence Similarities
Belongs to the cytochrome P450 family.
Cellular localization
- Mitochondrion inner membrane
- Peripheral membrane protein
- Localizes to the matrix side of the mitochondrion inner membrane.
Alternative names
CYP11A, CYP11A1, CYPXIA1, Cholesterol desmolase, Cytochrome P450 11A1, Cytochrome P450(scc)