Defective CYP11A1 does not cleave 20a,22b-DHCHOL

Stable Identifier
R-HSA-5580269
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1) normally catalyses the side-chain cleavage of cholesterol to form pregnenolone. CYP11A1 is the active unit of a complex comprising adrenodoxin reductase (FDXR), adrenodoxin (FDX, or adrenodoxin-like protein FDX1L) (Strushkevich et al. 2011). Defects in CYP11A1 can cause Adrenal insufficiency, congenital, with 46,XY sex reversal (AICSR; MIM:613743). This is a rare disorder that can present as acute adrenal insufficiency in infancy with elevated ACTH and plasma renin activity and low or absent adrenal steroids. Although milder forms can present, associated with partial loss of enzyme activity, the severest phenotype is associated with prematurity, complete underandrogenisation and severe, early-onset adrenal failure. CYP11A1 mutations causing complete loss of function are a 6bp insertion resulting in the insertion of glycine and aspartate codons, a 1bp deletion resulting in a premature stop at 288 and the missense mutation V415E (Tajima et al. 2001, Hiort et al. 2005, Kim et al. 2008, Sahakitrungruang et al. 2010).

Literature References
PubMed ID Title Journal Year
15507506 Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure

Hiort, O, Holterhus, PM, Werner, R, Marschke, C, Hoppe, U, Partsch, CJ, Riepe, FG, Achermann, JC, Struve, D

J. Clin. Endocrinol. Metab. 2005
21636783 Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system

Strushkevich, N, MacKenzie, F, Cherkesova, T, Grabovec, I, Usanov, S, Park, HW

Proc. Natl. Acad. Sci. U.S.A. 2011
11502818 Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency

Tajima, T, Fujieda, K, Kouda, N, Nakae, J, Miller, WL

J. Clin. Endocrinol. Metab. 2001
21159840 Partial defect in the cholesterol side-chain cleavage enzyme P450scc (CYP11A1) resembling nonclassic congenital lipoid adrenal hyperplasia

Sahakitrungruang, T, Tee, MK, Blackett, PR, Miller, WL

J. Clin. Endocrinol. Metab. 2011
Participants
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Disease
Name Identifier Synonyms
congenital adrenal insufficiency 0050546 ADRENAL INSUFFICIENCY, CONGENITAL, WITH 46,XY SEX REVERSAL, PARTIAL OR COMPLETE, P450scc DEFICIENCY
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