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Pathway Description
NAD Metabolism
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2016-01-21
Last Updated: 2019-08-14
The NAD biosynthesis begins with L-tryptophan interacting with oxygen through an indeleoamine 2,3-dioxygenase resulting in the release of N-formylkynurenine. This compound reacts with water through a kynurenine formamidase resulting in the release of formic acid, a hydrogen ion andL-kynurenine. The latter compound reacts with oxygen, hydrogen ion, NADPH through a kynurenine 3-monoxygenase resulting in the release of water, NADP and 3-hydroxy-L-kynurenine. The latter compound reacts with water through a kynureninase resulting in the release of L-alanine, hydrogen ion and 3-hydroxyanthranillic acid. The latter compound reacts with oxygen through a 3-hydroxyanthranilate 3,4-dioxygenase resulting in the release of hydrogen ion and 3-amino-3-carboxymuconic acid semialdehyde. The latter compound then spontaneously releases water and quinolinic acid. Quinolinic acid reacts with PRPP and hydrogen ion through a nicotinate-nucleotide pyrophosphorylase resulting in the release of carbon dioxide, pyrophosphate and nicotinate beta-D-ribonucleotide.
Nicotinate beta-D-ribonucleotide can also result from two other set of reactions: a) Nicotinate D-ribonucleoside being phosphorylated through an ATP dependent nicotinamide riboside kinase resulting in the release of ADP, hydrogen ion and nicotinate beta-D-ribonucleotide. b) nicotinamide riboside react with water through uridine nucleosidase resulting in the release of D-Ribose, hydrogen ion and niacinamide. Niacinamide react with water through nicotinamidase resulting in the release of ammonium and nicotinic acid. Nicotinic acid reacts with PRPP , water and ATP through a nicotinate phosphoribosyltransferase resulting in the release of pyrophosphate, ADP, phosphaste and nicotinate beta-D-ribonucleotide.
Nicotinate beta-D-ribonucleotide reacts with ATP and hydrogen ion through a nicotinamide/nicotinic acid mononucleotide adenylyltransferase resulting in the release of pyrophosphate and nicotinic acid adenine dinucleotide. The latter compound reacts with glutamine, water, and ATP through a glutamine dependent NAD synthetase resulting in the release of pyrophosphate, AMP, hydrogen ion, glutamic acid and NAD.
NAD can also be biosynthesized through a nicotinamide riboside being phosphorylated through an ATP driven nicotinamide riboside kinase resulting in the release of ADP, hydrogen ion and nicotinamide ribotide. The latter compound reacts with ATP and a hydrogen ion through a nicotinamid acid mononucleotide adenylyltransferase resulting in the release of a pyrophosphate and NAD.
NAD is degraded through a NAD dependent histone deacetylase resulting in SIR2 resulting in the release of 3-O acetyl ADP-ribose and niacinamide which can be incorporated into the pathway.
References
NAD Metabolism References
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Pubmed: 14977569
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Pubmed: 12062417
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Emanuelli M, Carnevali F, Lorenzi M, Raffaelli N, Amici A, Ruggieri S, Magni G: Identification and characterization of YLR328W, the Saccharomyces cerevisiae structural gene encoding NMN adenylyltransferase. Expression and characterization of the recombinant enzyme. FEBS Lett. 1999 Jul 16;455(1-2):13-7. doi: 10.1016/s0014-5793(99)00852-2.
Pubmed: 10428462
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Pubmed: 9169869
Emanuelli M, Amici A, Carnevali F, Pierella F, Raffaelli N, Magni G: Identification and characterization of a second NMN adenylyltransferase gene in Saccharomyces cerevisiae. Protein Expr Purif. 2003 Feb;27(2):357-64.
Pubmed: 12597897
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
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Pubmed: 14562106
Zagulski M, Babinska B, Gromadka R, Migdalski A, Rytka J, Sulicka J, Herbert CJ: The sequence of 24.3 kb from chromosome X reveals five complete open reading frames, all of which correspond to new genes, and a tandem insertion of a Ty1 transposon. Yeast. 1995 Sep 30;11(12):1179-86. doi: 10.1002/yea.320111208.
Pubmed: 8619316
Galibert F, Alexandraki D, Baur A, Boles E, Chalwatzis N, Chuat JC, Coster F, Cziepluch C, De Haan M, Domdey H, Durand P, Entian KD, Gatius M, Goffeau A, Grivell LA, Hennemann A, Herbert CJ, Heumann K, Hilger F, Hollenberg CP, Huang ME, Jacq C, Jauniaux JC, Katsoulou C, Karpfinger-Hartl L, et al.: Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X. EMBO J. 1996 May 1;15(9):2031-49.
Pubmed: 8641269
Panozzo C, Nawara M, Suski C, Kucharczyka R, Skoneczny M, Becam AM, Rytka J, Herbert CJ: Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae. FEBS Lett. 2002 Apr 24;517(1-3):97-102. doi: 10.1016/s0014-5793(02)02585-1.
Pubmed: 12062417
Obermaier B, Gassenhuber J, Piravandi E, Domdey H: Sequence analysis of a 78.6 kb segment of the left end of Saccharomyces cerevisiae chromosome II. Yeast. 1995 Sep 15;11(11):1103-12. doi: 10.1002/yea.320111112.
Pubmed: 7502586
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Pubmed: 7813418
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
Baxter SM, Rosenblum JS, Knutson S, Nelson MR, Montimurro JS, Di Gennaro JA, Speir JA, Burbaum JJ, Fetrow JS: Synergistic computational and experimental proteomics approaches for more accurate detection of active serine hydrolases in yeast. Mol Cell Proteomics. 2004 Mar;3(3):209-25. doi: 10.1074/mcp.M300082-MCP200. Epub 2003 Nov 25.
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Huang ME, Manus V, Chuat JC, Galibert F: Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading frames and a gene cluster with a counterpart on chromosome XI. Yeast. 1996 Jul;12(9):869-75. doi: 10.1002/(SICI)1097-0061(199607)12:9%3C869::AID-YEA964%3E3.0.CO;2-1.
Pubmed: 8840504
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