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Pathway Description
Cholesterol Biosynthesis and Metabolism
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-01
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 an acyl-CoA spontaneously resulting in the release of coenzyme A and a cholesteryl ester.
References
Cholesterol Biosynthesis and Metabolism References
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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.
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