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Pathway Description
Terpenoid Backbone 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.
Farnesyl diphosphate has three different fates:
1.-Producing hexaprenyl diphosphate in the mitocondrial inner membrane by reacting with 3 isopentenyl diphosphate
2.-Producing geranylgeranyl diphosphate in the cytoplasm by reacting with one isopentenyl diphosphate
3.-Producing a dolichol precursor in the ER by reacting with 13 isopentenyl diphosphates.
References
Terpenoid Backbone Biosynthesis References
Sato M, Fujisaki S, Sato K, Nishimura Y, Nakano A: Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different properties and localizations. Implication for their distinct physiological roles in dolichol synthesis. Genes Cells. 2001 Jun;6(6):495-506.
Pubmed: 11442630
Rodriguez-Concepcion M, Boronat A: Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics. Plant Physiol. 2002 Nov;130(3):1079-89. doi: 10.1104/pp.007138.
Pubmed: 12427975
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
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