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MetaCyc Pathway: pregnenolone biosynthesis
Inferred from experiment

Pathway diagram: pregnenolone biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisHormones Biosynthesis

Some taxa known to possess this pathway include : Homo sapiens

Expected Taxonomic Range: Vertebrata

Pregnenolone is synthesized in the mitochondrial inner membrane and is the biosynthetic precursor of all steroid hormones--androgens, estrogens, mineralo-and gluco-corticoids. Cholesterol is released from lipid droplets or endosomes and transported to the mitochondria by carrier proteins. The rate limiting step for steroid hormone synthesis is the transport of cholesterol from the outer to inner mitochondrial membrane by the steroidogenic acute regulatory protein (StAR) [Miller07]. StAR functions at the outer mitochondrial membrane to bind and release cholesterol during a pH mediated molten globule confirmational change [Bose99]. The cytosolic carrier proteins, StARD4, -5 and -6, contain a StAR-related lipid binding domain and exhibit tissue specific expression patterns [Soccio03]. The conversion of cholesterol to pregnenolone is catalyzed in three distinct reactions by a single cytochrome p450 enzyme CYP11A1.

Superpathways: superpathway of steroid hormone biosynthesis

Created 26-Jul-2010 by Trupp M, SRI International


Bose99: Bose HS, Whittal RM, Baldwin MA, Miller WL (1999). "The active form of the steroidogenic acute regulatory protein, StAR, appears to be a molten globule." Proc Natl Acad Sci U S A 96(13);7250-5. PMID: 10377400

Miller07: Miller WL (2007). "StAR search--what we know about how the steroidogenic acute regulatory protein mediates mitochondrial cholesterol import." Mol Endocrinol 21(3);589-601. PMID: 16973755

Soccio03: Soccio RE, Breslow JL (2003). "StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism." J Biol Chem 278(25);22183-6. PMID: 12724317

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Bloch65: Bloch K (1965). "The biological synthesis of cholesterol." Science 150(692);19-28. PMID: 5319508

Bloch92: Bloch K (1992). "Sterol molecule: structure, biosynthesis, and function." Steroids 57(8);378-83. PMID: 1519268

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

Fujita06: Fujita S, Ohnishi T, Watanabe B, Yokota T, Takatsuto S, Fujioka S, Yoshida S, Sakata K, Mizutani M (2006). "Arabidopsis CYP90B1 catalyses the early C-22 hydroxylation of C27, C28 and C29 sterols." Plant J 45(5);765-74. PMID: 16460510

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

Knopp99: Knopp RH (1999). "Drug treatment of lipid disorders." N Engl J Med 341(7);498-511. PMID: 10441607

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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

Vance00: Vance DE, Van den Bosch H (2000). "Cholesterol in the year 2000." Biochim Biophys Acta 1529(1-3);1-8. PMID: 11111073

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

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 19.5 on Sat Feb 13, 2016, BIOCYC11A.