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Pathway Description
Lysine Metabolism
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2016-01-19
Last Updated: 2019-08-14
The biosynthesis of lysine starts with oxoglutaric acid interacting with acetyl-coa through a homocitrate synthase resulting in the release of homocitric acid. This reaction may happen in the cytosol or in the mitochondria. The homocitric acid spontaneously releases water an is transformed into cis-homoaconitate, The cis-homoaconitate reacts with homoaconitase resulting in the release of water and a homoisocitrate. Homoisocitrate reacts with a NAD dependent homoisocitrate dehydrogenase resulting in the release of a carbon dioxide, a NADH and a oxoadipic acid. These set of reactions happen in the mitochondria. Oxoadipic acid reacts with a glutamic acid resulting in the release of oxoglutaric acid and aminoadipic acid. The aminoadipic acid reacts with a holo-[LYS2 peptidyl-carrier-protein] through an ATP driven L-2-aminoadipate reductase resulting in the release of AMP, pyrophosphate and L-2-aminoadipyl-[lys2 peptidyl-carrier-protein]. This resulting element reacts with a NADPH dependent L-2-aminoadipate reductase resulting in the release of allysine. Allysine reacts with a glutamic acid through a NADPH dependent saccharopine dehydrogenase resulting in the release of water, NADP and saccharopine. Saccharopine reacts with a water molecule and a NAD dependent saccharopine dehydrogenase resulting in the release of oxoglutaric acid and L-lysine. This last reaction is reversible and leads to the degradation of lysine
References
Lysine Metabolism References
El Alami M, Feller A, Pierard A, Dubois E: Characterisation of a tripartite nuclear localisation sequence in the regulatory protein Lys14 of Saccharomyces cerevisiae. Curr Genet. 2000 Aug;38(2):78-86.
Pubmed: 10975256
Feller A, Ramos F, Pierard A, Dubois E: In Saccharomyces cerevisae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p. Eur J Biochem. 1999 Apr;261(1):163-70.
Pubmed: 10103047
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.
Ehmann DE, Gehring AM, Walsh CT: Lysine biosynthesis in Saccharomyces cerevisiae: mechanism of alpha-aminoadipate reductase (Lys2) involves posttranslational phosphopantetheinylation by Lys5. Biochemistry. 1999 May 11;38(19):6171-7. doi: 10.1021/bi9829940.
Pubmed: 10320345
Wolfl S, Hanemann V, Saluz HP: Analysis of a 26,756 bp segment from the left arm of yeast chromosome IV. Yeast. 1996 Dec;12(15):1549-54. doi: 10.1002/(SICI)1097-0061(199612)12:15%3C1549::AID-YEA42%3E3.0.CO;2-S.
Pubmed: 8972577
Jacq C, Alt-Morbe J, Andre B, Arnold W, Bahr A, Ballesta JP, Bargues M, Baron L, Becker A, Biteau N, Blocker H, Blugeon C, Boskovic J, Brandt P, Bruckner M, Buitrago MJ, Coster F, Delaveau T, del Rey F, Dujon B, Eide LG, Garcia-Cantalejo JM, Goffeau A, Gomez-Peris A, Zaccaria P, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome IV. Nature. 1997 May 29;387(6632 Suppl):75-8.
Pubmed: 9169867
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
Verhasselt P, Voet M, Volckaert G: New open reading frames, one of which is similar to the nifV gene of Azotobacter vinelandii, found on a 12.5 kbp fragment of chromosome IV of Saccharomyces cerevisiae. Yeast. 1995 Aug;11(10):961-6. doi: 10.1002/yea.320111007.
Pubmed: 8533471
Irvin SD, Bhattacharjee JK: A unique fungal lysine biosynthesis enzyme shares a common ancestor with tricarboxylic acid cycle and leucine biosynthetic enzymes found in diverse organisms. J Mol Evol. 1998 Apr;46(4):401-8.
Pubmed: 9541534
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
Strassman M, Ceci LN: Enzymatic formation of alpha-ketoadipic acid from homoisocitric acid. J Biol Chem. 1965 Nov;240(11):4357-61.
Pubmed: 4284830
Morris ME, Jinks-Robertson S: Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase 1. Gene. 1991 Feb 1;98(1):141-5. doi: 10.1016/0378-1119(91)90117-t.
Pubmed: 2013406
Fleig UN, Pridmore RD, Philippsen P: Construction of LYS2 cartridges for use in genetic manipulations of Saccharomyces cerevisiae. Gene. 1986;46(2-3):237-45. doi: 10.1016/0378-1119(86)90408-7.
Pubmed: 3542721
Mannhaupt G, Stucka R, Ehnle S, Vetter I, Feldmann H: Molecular analysis of yeast chromosome II between CMD1 and LYS2: the excision repair gene RAD16 located in this region belongs to a novel group of double-finger proteins. Yeast. 1992 May;8(5):397-408. doi: 10.1002/yea.320080507.
Pubmed: 1626431
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
Hu Y, Rolfs A, Bhullar B, Murthy TV, Zhu C, Berger MF, Camargo AA, Kelley F, McCarron S, Jepson D, Richardson A, Raphael J, Moreira D, Taycher E, Zuo D, Mohr S, Kane MF, Williamson J, Simpson A, Bulyk ML, Harlow E, Marsischky G, Kolodner RD, LaBaer J: Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae. Genome Res. 2007 Apr;17(4):536-43. doi: 10.1101/gr.6037607. Epub 2007 Feb 23.
Pubmed: 17322287
Ramos F, Dubois E, Pierard A: Control of enzyme synthesis in the lysine biosynthetic pathway of Saccharomyces cerevisiae. Evidence for a regulatory role of gene LYS14. Eur J Biochem. 1988 Jan 15;171(1-2):171-6. doi: 10.1111/j.1432-1033.1988.tb13773.x.
Pubmed: 3123231
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