Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Cholesterol Biosynthesis and Metabolism CE(12:0)
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2016-05-17
Last Updated: 2019-08-29
The biosynthesis of Cholesterol starts with acetyl-CoA reacts with acetyl-CoA c-acetyltransferase resulting in the release of CoA acetoacetyl-CoA, The latter compound then reacts with an acetyl-coa through a hydroxymethylglutaryl-CoA synthase resulting in the release of 3-hydroxy-3-methylglutaryl-CoA. The latter compound in turn reacts with a NADPH through a 3-hydroxy-3-methylglutaryl-coenzyme A reductase resulting in the release of a NADP, Coenzyme A and Mevalonic acid. The latter is then phosphorylated by ATP through a mevalonate kinase resulting in the release of ADP and Mevalonic acid-5P which is then phosphorylated by ATP through a phosphomevalonate kinase resulting in the release of ADP and (S)-5-diphosphomevalonic acid. The latter compound in turn reacts with ATP through a diphosphomevalonic decarboxylase resulting in the release of phosphate, ADP, carbon dioxide and Isopentenyl pyrophosphate. The latter compound in turn reacts with isopentenyl diphosphate delta isomerase resulting in the release of dimethylallylpyrophosphate. The latter compound then reacts with isopentenyl pyrophosphate through a farnesyl pyrophosphate synthase resulting in the release of Geranyl-PP. The latter then reacts with an isopentenyl pyrophosphate through farnesyl pyrophosphate synthase resulting in the release of pyrophospate and farnesyl pyrophosphate. Farnesyl pyrophosphate then reacts with NADPH through a squalene synthase in order to produce squalene while also releasing two phosphates and NADP. Squalene then reacts with oxygen and NADPH through a squalene monooxygenase resulting in the release of water, NADP and (S)-2,3-epoxysqualene. The latter in turn reacts with lanosterol synthase resulting in the release of lanosterin. Lanosterin then reacts with oxygen and NADPH through a lanosterol 14-alpha demethylase resulting in the release of formic acid, water, NADP and 4,4-dimethylcholesta-8,14,24-trienol. The latter compound in turn is reduced by an NADPH through a Delta (14)-sterol reductase resulting in the release of NADP and 4,4-dimethyl-5a-cholesta-8,24-dien-3-b-ol. The latter reacts with hydrogen ion,oxygen and NADPH through a methylsterol monooxygenase resulting in the release of NADP, water and 4a-hydroxymethyl-4B-methyl-5a-cholesta-8,24-dien-3B-ol. The latter compound reacts with a hydrogen ion, water, and NADPH through a methylsterol monooxygenase resulting in the release of NADP, water and 4a-formyl-4b-methyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with oxygen, NADPH through methylsterol monooxygenase resulting in the release of water, NADP and 4B-methyl-4a-carboxy-cholesta-8,24-dien-3B-ol. The latter reacts with an NADP through c-3 sterol dehydrogenase resulting in the release of NADPH, carbon dioxide and 3-keto-4-methylzymosterol. The latter is reduced by NADPH through a 3-keto sterol reductase resulting in the release of NADP and 4a-methylzymosterol. The latter then reacts with hydrogen, oxygen and nadph through methylsterol monooxygenase resulting in the release of water, NADP and 4a-hydroxymethyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with water, hydrogen and NADPH through a methylsterol monooxygenase resulting in the release of water, NADP and 4a-formyl-5a-cholesta-8,24-dien-3B-ol. The latter reacts with oxygen and NADPH through methylsterol monooxygenase resulting in the release of water, NADP and 4a-carboxy-5a-cholesta-8,24-dien-3B-ol. The latter compound reacts with NADP through a C-3 sterol dehydrogenase resulting in the release of carbon dioxide, NADPH and 5a-cholesta-8,24-dien-3-one. The latter reacts with hydrogen ion and NADPH through a 3-keto sterol reductase resulting in the release of NADP and zymosterol. Zymosterol can either be used to create ergosterol starts with zymosterol reacting with S-adenosylmethionine through a sterol 24-c-methyltransferase resulting in the release of S-adenosylhomocysteine, hydrogen ion and fecosterol. Fecosterol reacts with C-8 sterol isomerase resulting in the release of episterol. Episterol reacts with oxygen, hydrogen ion and ferrocytochrome c through a C-5 sterol desaturase resulting in the release of ferricytochrome c, water and 5,7,24(28)-ergostatrienol. The latter reacts with hydrogen ion, oxygen, NADPH and c-22 sterol desaturase resulting in the release of water, NADP AND ERGOSTA-5,7,22,24(28)-tetraen-3-B-ol. The latter compound reacts with hydrogen ion and NADPH through a C-24 sterol reductase resulting in the release of NADP and ergosterol. Zymosterol reacts with C-8 sterol isomerase resulting in the release of 5a-cholesta-7,24-dien-3b-ol. The latter compound reacts with C-5 sterol desaturase resulting in the release of 7-dehydrodesmosterol. The latter is then converted spontaneously through desmosterol. Desmosterol is then spontaneously turned into cholesterol which can in turn react with Dodecanoic acid spontaneously resulting in the release of Coenzyme A and CE(12:0).
References
Cholesterol Biosynthesis and Metabolism CE(12:0) References
Einerhand AW, Voorn-Brouwer TM, Erdmann R, Kunau WH, Tabak HF: Regulation of transcription of the gene coding for peroxisomal 3-oxoacyl-CoA thiolase of Saccharomyces cerevisiae. Eur J Biochem. 1991 Aug 15;200(1):113-22. doi: 10.1111/j.1432-1033.1991.tb21056.x.
Pubmed: 1715273
Igual JC, Matallana E, Gonzalez-Bosch C, Franco L, Perez-Ortin JE: A new glucose-repressible gene identified from the analysis of chromatin structure in deletion mutants of yeast SUC2 locus. Yeast. 1991 May-Jun;7(4):379-89. doi: 10.1002/yea.320070408.
Pubmed: 1872029
Churcher C, Bowman S, Badcock K, Bankier A, Brown D, Chillingworth T, Connor R, Devlin K, Gentles S, Hamlin N, Harris D, Horsnell T, Hunt S, Jagels K, Jones M, Lye G, Moule S, Odell C, Pearson D, Rajandream M, Rice P, Rowley N, Skelton J, Smith V, Barrell B, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome IX. Nature. 1997 May 29;387(6632 Suppl):84-7.
Pubmed: 9169870
Basson ME, Thorsness M, Finer-Moore J, Stroud RM, Rine J: Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol. 1988 Sep;8(9):3797-808. doi: 10.1128/mcb.8.9.3797.
Pubmed: 3065625
Johnston M, Hillier L, Riles L, Albermann K, Andre B, Ansorge W, Benes V, Bruckner M, Delius H, Dubois E, Dusterhoft A, Entian KD, Floeth M, Goffeau A, Hebling U, Heumann K, Heuss-Neitzel D, Hilbert H, Hilger F, Kleine K, Kotter P, Louis EJ, Messenguy F, Mewes HW, Hoheisel JD, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome XII. Nature. 1997 May 29;387(6632 Suppl):87-90.
Pubmed: 9169871
Engel SR, Dietrich FS, Fisk DG, Binkley G, Balakrishnan R, Costanzo MC, Dwight SS, Hitz BC, Karra K, Nash RS, Weng S, Wong ED, Lloyd P, Skrzypek MS, Miyasato SR, Simison M, Cherry JM: The reference genome sequence of Saccharomyces cerevisiae: then and now. G3 (Bethesda). 2014 Mar 20;4(3):389-98. doi: 10.1534/g3.113.008995.
Pubmed: 24374639
Bowman S, Churcher C, Badcock K, Brown D, Chillingworth T, Connor R, Dedman K, Devlin K, Gentles S, Hamlin N, Hunt S, Jagels K, Lye G, Moule S, Odell C, Pearson D, Rajandream M, Rice P, Skelton J, Walsh S, Whitehead S, Barrell B: The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII. Nature. 1997 May 29;387(6632 Suppl):90-3.
Pubmed: 9169872
Kalb VF, Woods CW, Turi TG, Dey CR, Sutter TR, Loper JC: Primary structure of the P450 lanosterol demethylase gene from Saccharomyces cerevisiae. DNA. 1987 Dec;6(6):529-37. doi: 10.1089/dna.1987.6.529.
Pubmed: 3322742
Ishida N, Aoyama Y, Hatanaka R, Oyama Y, Imajo S, Ishiguro M, Oshima T, Nakazato H, Noguchi T, Maitra US, et al.: A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS. Biochem Biophys Res Commun. 1988 Aug 30;155(1):317-23. doi: 10.1016/s0006-291x(88)81087-8.
Pubmed: 3046615
Johnston M, Andrews S, Brinkman R, Cooper J, Ding H, Dover J, Du Z, Favello A, Fulton L, Gattung S, et al.: Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science. 1994 Sep 30;265(5181):2077-82. doi: 10.1126/science.8091229.
Pubmed: 8091229
Lorenz RT, Parks LW: Cloning, sequencing, and disruption of the gene encoding sterol C-14 reductase in Saccharomyces cerevisiae. DNA Cell Biol. 1992 Nov;11(9):685-92. doi: 10.1089/dna.1992.11.685.
Pubmed: 1418625
Lai MH, Bard M, Pierson CA, Alexander JF, Goebl M, Carter GT, Kirsch DR: The identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway. Gene. 1994 Mar 11;140(1):41-9. doi: 10.1016/0378-1119(94)90728-5.
Pubmed: 8125337
Philippsen P, Kleine K, Pohlmann R, Dusterhoft A, Hamberg K, Hegemann JH, Obermaier B, Urrestarazu LA, Aert R, Albermann K, Altmann R, Andre B, Baladron V, Ballesta JP, Becam AM, Beinhauer J, Boskovic J, Buitrago MJ, Bussereau F, Coster F, Crouzet M, D'Angelo M, Dal Pero F, De Antoni A, Del Rey F, Doignon F, Domdey H, Dubois E, Fiedler T, Fleig U, Floeth M, Fritz C, Gaillardin C, Garcia-Cantalejo JM, Glansdorff NN, Goffeau A, Gueldener U, Herbert C, Heumann K, Heuss-Neitzel D, Hilbert H, Hinni K, Iraqui Houssaini I, Jacquet M, Jimenez A, Jonniaux JL, Karpfinger L, Lanfranchi G, Lepingle A, Levesque H, Lyck R, Maftahi M, Mallet L, Maurer KC, Messenguy F, Mewes HW, Mosti D, Nasr F, Nicaud JM, Niedenthal RK, Pandolfo D, Pierard A, Piravandi E, Planta RJ, Pohl TM, Purnelle B, Rebischung C, Remacha M, Revuelta JL, Rinke M, Saiz JE, Sartorello F, Scherens B, Sen-Gupta M, Soler-Mira A, Urbanus JH, Valle G, Van Dyck L, Verhasselt P, Vierendeels F, Vissers S, Voet M, Volckaert G, Wach A, Wambutt R, Wedler H, Zollner A, Hani J: The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications. Nature. 1997 May 29;387(6632 Suppl):93-8.
Pubmed: 9169873
Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature. 2003 Oct 16;425(6959):737-41. doi: 10.1038/nature02046.
Pubmed: 14562106
Oulmouden A, Karst F: Nucleotide sequence of the ERG12 gene of Saccharomyces cerevisiae encoding mevalonate kinase. Curr Genet. 1991 Jan;19(1):9-14.
Pubmed: 1645230
Kearsey SE, Edwards J: Mutations that increase the mitotic stability of minichromosomes in yeast: characterization of RAR1. Mol Gen Genet. 1987 Dec;210(3):509-17. doi: 10.1007/bf00327205.
Pubmed: 3323847
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. doi: 10.1128/mcb.11.2.620.
Pubmed: 1846667
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. doi: 10.1074/jbc.271.14.7895.
Pubmed: 8626466
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. doi: 10.1128/jb.179.15.4664-4670.1997.
Pubmed: 9244250
This pathway was generated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Generated from SMP0070041
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