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Pathway Description
Leucine Biosynthesis
Saccharomyces cerevisiae
Metabolic Pathway
Leucine biosynthesis involves a five-step conversion process starting with the valine precursor 2-keto-isovalerate interacting with acetyl-CoA and water through a 2-isopropylmalate synthase resulting in Coenzyme A, hydrogen Ion and 2-isopropylmalic acid. The latter compound reacts with isopropylmalate isomerase which dehydrates the compound resulting in a Isopropylmaleate. This compound reacts with water through a isopropylmalate isomerase resulting in 3-isopropylmalate. This compound interacts with a NAD-driven D-malate / 3-isopropylmalate dehydrogenase results in 2-isopropyl-3-oxosuccinate. This compound interacts spontaneously with hydrogen resulting in the release of carbon dioxide and ketoleucine. Ketoleucine interacts in a reversible reaction with L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in Oxoglutaric acid and L-leucine. L-leucine can then be exported outside the cytoplasm through a transporter: L-amino acid efflux transporter. In the final step, ketoleucine can be catalyzed to form L-leucine by branched-chain amino-acid aminotransferase (IlvE) and tyrosine aminotransferase (TryB). L-Glutamic acid can also be transformed into oxoglutaric acid by these two enzymes. Tyrosine aminotransferase can be suppressed by lecuine, and inhibited by 2-keto-isovarlerate and its end product, tyrosine. 2-ketoisocaproate can not be introduced if 2-keto-isovarlerate inhibit TyrB and IlvE is absent.
References
Leucine Biosynthesis References
Andreadis A, Hsu YP, Hermodson M, Kohlhaw G, Schimmel P: Yeast LEU2. Repression of mRNA levels by leucine and primary structure of the gene product. J Biol Chem. 1984 Jul 10;259(13):8059-62.
Pubmed: 6330094
Bollon AP: Regulation of the ilv 1 multifunctional gene in Saccharomyces cerevisiae. Mol Gen Genet. 1975 Dec 23;142(1):1-12.
Pubmed: 765733
Branduardi P, Longo V, Berterame NM, Rossi G, Porro D: A novel pathway to produce butanol and isobutanol in Saccharomyces cerevisiae. Biotechnol Biofuels. 2013 May 4;6(1):68. doi: 10.1186/1754-6834-6-68.
Pubmed: 23642236
Eden A, Simchen G, Benvenisty N: Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases. J Biol Chem. 1996 Aug 23;271(34):20242-5.
Pubmed: 8702755
Hinnebusch, A. General and pathway-specific regulatory mechanisms controlling the synthesis of amino acid biosynthetic enzymes in Saccharomyces cerevisiae. The Molecular and Cellular Biology of the yeast Saccharomyces: Gene Expression. 1992;2:319-414.
Kohlhaw GB: Leucine biosynthesis in fungi: entering metabolism through the back door. Microbiol Mol Biol Rev. 2003 Mar;67(1):1-15, table of contents.
Pubmed: 12626680
Storms RK, Holowachuck EW, Friesen JD: Genetic complementation of the Saccharomyces cerevisiae leu2 gene by the Escherichia coli leuB gene. Mol Cell Biol. 1981 Sep;1(9):836-42.
Pubmed: 9279396
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