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MetaCyc Enzyme: cholesterol side chain cleavage enzyme, mitochondrial

Gene: CYP11A1 Accession Number: HS06719 (MetaCyc)

Synonyms: CYP11A, Cholesterol desmolase, CYPXIA1, Cytochrome P450 11A1, P450(scc)

Species: Homo sapiens

Summary:
CYP11A1 encodes a member of the cytochrome P450 superfamily of heme containing membrane associated enzymes. These proteins function as monooxygenases utilizing NADPH for the reduction of molecular oxygen via a membrane bound electron transfer system. CYP11A1 localizes to the mitochondrial inner membrane and catalyzes the conversion of cholesterol to pregnenolone in three distinct reactions at a single active site. [Chung86, Strushkevich11]. In these reactions the electrons from NADPH are transferred to a flavin containing protein, ferredoxin reductase and subsequently to ferredoxin (a non-heme iron-sulfur protein), to CYP11A1 and finally to activate the oxygen substrate [Vickery97].

Defects in CYP11A1 cause congenital adrenal insufficiency and ipoid adrenal hyperplasia (CLAH)(OMIM: 201710). These mutations are potentially lethal but rare, except in Japan and Korea, where they account for a significant proportion of adrenal hyperplasia cases [Matteson86].

Citations: [BenZimra02, Tuckey02, Gizard02, Doi02, Gharani97, Helmberg93, Morohashi87, Sparkes91]

Locations: membrane, mitochondrion

Map Position: [67,746,229 <- 67,773,989]

Unification Links: ArrayExpress:P05108 , Ensembl:ENSG00000140459 , Entrez-gene:1583 , Entrez-Nucleotide:AK056794 , Entrez-Nucleotide:BC032329 , Entrez-Nucleotide:D00169 , Entrez-Nucleotide:M14565 , Entrez-Nucleotide:M28253 , Entrez-Nucleotide:X05367 , Entrez-Nucleotide:X14257 , Entrez:AAA36404 , Entrez:AAA52162 , Entrez:AAH32329 , Entrez:BAA00119 , Entrez:CAA28965 , Entrez:CAA32471 , Mint:MINT-1200919 , OMIM:118485 , OMIM:201710 , PhosphoSite:P05108 , Pride:P05108 , Protein Model Portal:P05108 , RefSeq:NM_000781 , RefSeq:NP_000772 , SMR:P05108 , String:9606.ENSP00000268053 , UCSC Human Genome:NM_000781 , UniGene:76205 , UniProt:P05108

Relationship Links: InterPro:IN-FAMILY:IPR001128 , InterPro:IN-FAMILY:IPR002401 , InterPro:IN-FAMILY:IPR017972 , PDB:Structure:3N9Y , PDB:Structure:3N9Z , PDB:Structure:3NA0 , PDB:Structure:3NA1 , Pfam:IN-FAMILY:PF00067 , Prints:IN-FAMILY:PR00385 , Prints:IN-FAMILY:PR00463 , Prosite:IN-FAMILY:PS00086

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006694 - steroid biosynthetic process
GO:0006700 - C21-steroid hormone biosynthetic process
GO:0006702 - androgen biosynthetic process
Molecular Function: GO:0004497 - monooxygenase activity
GO:0008386 - cholesterol monooxygenase (side-chain-cleaving) activity
Cellular Component: GO:0005739 - mitochondrion
GO:0016020 - membrane


Enzymatic reaction of: 20-α-22-β-dihydroxycholesterol side-chain lyase (cholesterol side chain cleavage enzyme, mitochondrial)

EC Number: 1.14.15.6

(20R,22R)-dihydroxycholesterol + 2 a reduced adrenodoxin + oxygen + 2 H+ <=> pregnenolone + 4-methylpentanal + 2 an oxidized adrenodoxin + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , pregnenolone biosynthesis


Enzymatic reaction of: 22-β-hydroxycholesterol 20-α-hydroxylase (cholesterol side chain cleavage enzyme, mitochondrial)

EC Number: 1.14.15.6

(22R)-hydroxycholesterol + 2 a reduced adrenodoxin + oxygen + 2 H+ <=> (20R,22R)-dihydroxycholesterol + 2 an oxidized adrenodoxin + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , pregnenolone biosynthesis


Enzymatic reaction of: cholesterol 22-β-hydroxylase (cholesterol side chain cleavage enzyme, mitochondrial)

EC Number: 1.14.15.6

cholesterol + 2 a reduced adrenodoxin + oxygen + 2 H+ <=> (22R)-hydroxycholesterol + 2 an oxidized adrenodoxin + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , pregnenolone biosynthesis


Enzymatic reaction of: Cholesterol side-chain cleavage enzyme, mitochondrial (cholesterol side chain cleavage enzyme, mitochondrial)

EC Number: 1.14.15.6

cholesterol + 6 a reduced adrenodoxin + 3 oxygen + 6 H+ <=> pregnenolone + 4-methylpentanal + 6 an oxidized adrenodoxin + 4 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , pregnenolone biosynthesis

Exons/Introns:

Schematic showing introns, exons and/or isoforms of CYP11A1


References

BenZimra02: Ben-Zimra M, Koler M, Orly J (2002). "Transcription of cholesterol side-chain cleavage cytochrome P450 in the placenta: activating protein-2 assumes the role of steroidogenic factor-1 by binding to an overlapping promoter element." Mol Endocrinol 16(8);1864-80. PMID: 12145340

Chung86: Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL (1986). "Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta." Proc Natl Acad Sci U S A 83(23);8962-6. PMID: 3024157

Doi02: Doi J, Takemori H, Lin XZ, Horike N, Katoh Y, Okamoto M (2002). "Salt-inducible kinase represses cAMP-dependent protein kinase-mediated activation of human cholesterol side chain cleavage cytochrome P450 promoter through the CREB basic leucine zipper domain." J Biol Chem 277(18);15629-37. PMID: 11864972

Gharani97: Gharani N, Waterworth DM, Batty S, White D, Gilling-Smith C, Conway GS, McCarthy M, Franks S, Williamson R (1997). "Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism." Hum Mol Genet 6(3);397-402. PMID: 9147642

Gizard02: Gizard F, Lavallee B, DeWitte F, Teissier E, Staels B, Hum DW (2002). "The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells." J Biol Chem 277(42);39144-55. PMID: 12101186

Helmberg93: Helmberg A (1993). "Twin genes and endocrine disease: CYP21 and CYP11B genes." Acta Endocrinol (Copenh) 129(2);97-108. PMID: 8372604

Matteson86: Matteson KJ, Chung BC, Urdea MS, Miller WL (1986). "Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes." Endocrinology 118(4);1296-305. PMID: 2419119

Morohashi87: Morohashi K, Sogawa K, Omura T, Fujii-Kuriyama Y (1987). "Gene structure of human cytochrome P-450(SCC), cholesterol desmolase." J Biochem 101(4);879-87. PMID: 3038854

Sparkes91: Sparkes RS, Klisak I, Miller WL (1991). "Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25." DNA Cell Biol 10(5);359-65. PMID: 1863359

Strushkevich11: Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW (2011). "Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system." Proc Natl Acad Sci U S A 108(25);10139-43. PMID: 21636783

Tuckey02: Tuckey RC, Headlam MJ (2002). "Placental cytochrome P450scc (CYP11A1): comparison of catalytic properties between conditions of limiting and saturating adrenodoxin reductase." J Steroid Biochem Mol Biol 81(2);153-8. PMID: 12137805

Vickery97: Vickery LE (1997). "Molecular recognition and electron transfer in mitochondrial steroid hydroxylase systems." Steroids 62(1);124-7. PMID: 9029726

Woods98: Woods ST, Sadleir J, Downs T, Triantopoulos T, Headlam MJ, Tuckey RC (1998). "Expression of catalytically active human cytochrome p450scc in Escherichia coli and mutagenesis of isoleucine-462." Arch Biochem Biophys 353(1);109-15. PMID: 9578606


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Sat May 23, 2015, biocyc11.