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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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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: ?

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 Enzyme Commission system.

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 Enzyme Commission system.

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 Enzyme Commission system.

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 Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , pregnenolone biosynthesis

Exons/Introns:


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 18.5 on Fri Nov 28, 2014, biocyc14.