Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Steroid Biosynthesis
Saccharomyces cerevisiae
Metabolic Pathway
The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. The latter compound reacts with hydrogen ion, NADPH through a squalene synthetase resulting in the release NADP, pyrophosphate and squalene. The latter compound reacts with hydrogen ion NADPH and oxygen through squalene monooxygenase resulting in the release of NADP, Water and (3S)-2,3-epoxy-2,3-dihydrosqualene. The latter compound reacts through a 2,3-oxidosqualene lanosterol cyclase resulting in the release of lanosterol.
Lanosterol reacts with hydrogen ion, NADPH, and oxygen through a cytochrome P450 lanosterol 14a demethylase resulting in the release of formate, water, NADP and 14-demethyllanosterol. The latter compound reacts with hydrogen ion and NADPH through a c-14 sterol reductase resulting in the release of NADP and 4,4-dimethylzymosterol. The latter compound reacts with methylsterol monooxygenase resulting in the release of 4α-hydroxymethyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol which reacts with methylsterol monooxygenase twice to obtain 4α-carboxy-4β-methyl-5α-cholesta-8,24-dien-3β-ol. The latter compound then reacts with an NADP C-3 sterol dehydrogenase resulting in the release of water, NADP and 3-dehydro-4-methylzymosterol. The latter compound then reacts with NADPH and a hydrogen ion through a 3-keto sterol reductase resulting in the release of NADP and 4alpha-methyl-zymosterol. The latter compound then reacts with a methylsterol monooxygenase 3 times, followed by one reaction with c-sterol dehydrogenase and one reaction with 3-keto sterol reductase resulting in the release of a zymosterol. The latter compound reacts with SAM through a sterol methyltransferase resulting in the release of s-adenosylhomocysteine and fecosterol. Fecosterol is isomerized into episterol. The latter compound reacts with c-5 sterol desaturase resulting in the release of ergosta-5,7,24(28)-trien-3β-ol which then reacts with a c-22 sterol desaturase resulting in the release of ergosta-5,7,22,24(28)-tetraen-3-β-ol. This latter compound then reacts with a C-24 sterol reductase resulting in the release of an ergosterol.
References
Steroid Biosynthesis References
Berges T, Guyonnet D, Karst F: The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to thermosensitivity. J Bacteriol. 1997 Aug;179(15):4664-70.
Pubmed: 9244250
Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V, Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK: Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12896-901. doi: 10.1073/pnas.181466998.
Pubmed: 11698677
Chambon C, Ladeveze V, Servouse M, Blanchard L, Javelot C, Vladescu B, Karst F: Sterol pathway in yeast. Identification and properties of mutant strains defective in mevalonate diphosphate decarboxylase and farnesyl diphosphate synthetase. Lipids. 1991 Aug;26(8):633-6.
Pubmed: 1779710
Cordier H, Lacombe C, Karst F, Berges T: The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase (erg19p) forms homodimers in vivo, and a single substitution in a structurally conserved region impairs dimerization. Curr Microbiol. 1999 May;38(5):290-4.
Pubmed: 10355117
Krepkiy D, Miziorko HM: Identification of active site residues in mevalonate diphosphate decarboxylase: implications for a family of phosphotransferases. Protein Sci. 2004 Jul;13(7):1875-81. doi: 10.1110/ps.04725204. Epub 2004 May 28.
Pubmed: 15169949
Toth MJ, Huwyler L: Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase. J Biol Chem. 1996 Apr 5;271(14):7895-8.
Pubmed: 8626466
Tsay YH, Robinson GW: Cloning and characterization of ERG8, an essential gene of Saccharomyces cerevisiae that encodes phosphomevalonate kinase. Mol Cell Biol. 1991 Feb;11(2):620-31.
Pubmed: 1846667
Anderson MS, Yarger JG, Burck CL, Poulter CD: Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae. J Biol Chem. 1989 Nov 15;264(32):19176-84.
Pubmed: 2681213
Kelly GS: Squalene and its potential clinical uses. Altern Med Rev. 1999 Feb;4(1):29-36.
Pubmed: 9988781
Leber R, Fuchsbichler S, Klobucnikova V, Schweighofer N, Pitters E, Wohlfarter K, Lederer M, Landl K, Ruckenstuhl C, Hapala I, Turnowsky F: Molecular mechanism of terbinafine resistance in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2003 Dec;47(12):3890-900.
Pubmed: 14638499
Parks LW, Casey WM: Physiological implications of sterol biosynthesis in yeast. Annu Rev Microbiol. 1995;49:95-116. doi: 10.1146/annurev.mi.49.100195.000523.
Pubmed: 8561481
Bard M, Lees ND, Turi T, Craft D, Cofrin L, Barbuch R, Koegel C, Loper JC: Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans. Lipids. 1993 Nov;28(11):963-7.
Pubmed: 8277826
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Settings