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MetaCyc Pathway: superpathway of NAD biosynthesis in eukaryotes

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis NAD Metabolism NAD Biosynthesis
Superpathways

Some taxa known to possess this pathway include ? : Saccharomyces cerevisiae

Expected Taxonomic Range: Eukaryota

Summary:
NAD is an ubiquitous molecule that participates in many metabolic reactions. It also plays important roles in transcriptional regulation, longevity, calorie-restriction-mediated life-span extension and age-associated diseases. In yeast, it has been shown that NAD affects longevity and transcriptional silencing through the regulation of the Sir2p family of NAD-dependent deacetylases [Lin03, Lin04].

NAD is synthesised via two major pathways in eukaryotic systems. In the de novo pathway (NAD biosynthesis II (from tryptophan)), the nicotinic acid moiety of NAD is synthesized from tryptophan via the kynurenine pathway. In yeast, the de novo pathway consists of six enzymatic steps (catalyzed by the products of the BNA genes) and one non-enzymatic reaction.

In the NAD salvage pathway I, the nicotinate moiety of NAD is generated by the recycling of degraded NAD products such as nicotinamide [Panozzo02, Anderson02].

The two pathways converge at nicotinate nucleotide, and continue along the same path, generating NAD via deamido-NAD.

Subpathways: NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde , tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde , NAD biosynthesis II (from tryptophan) , NAD salvage pathway I

Variants: NAD biosynthesis I (from aspartate) , NAD biosynthesis III , NAD salvage pathway II , NAD salvage pathway III

Credits:
Created 27-Apr-2005 by Balakrishnan R , Hong E , Saccharomyces Genome Database
Reviewed 03-Apr-2006 by Caspi R , SRI International


References

Anderson02: Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA (2002). "Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels." J Biol Chem 277(21);18881-90. PMID: 11884393

Lin03: Lin SJ, Guarente L (2003). "Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease." Curr Opin Cell Biol 15(2);241-6. PMID: 12648681

Lin04: Lin SJ, Ford E, Haigis M, Liszt G, Guarente L (2004). "Calorie restriction extends yeast life span by lowering the level of NADH." Genes Dev 18(1);12-6. PMID: 14724176

Panozzo02: Panozzo C, Nawara M, Suski C, Kucharczyka R, Skoneczny M, Becam AM, Rytka J, Herbert CJ (2002). "Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae." FEBS Lett 517(1-3);97-102. PMID: 12062417

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

AlberatiGiani97: Alberati-Giani D, Cesura AM, Broger C, Warren WD, Rover S, Malherbe P (1997). "Cloning and functional expression of human kynurenine 3-monooxygenase." FEBS Lett 410(2-3);407-12. PMID: 9237672

Austin09: Austin CJ, Astelbauer F, Kosim-Satyaputra P, Ball HJ, Willows RD, Jamie JF, Hunt NH (2009). "Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties." Amino Acids 36(1);99-106. PMID: 18274832

Baecker78: Baecker PA, Yung SG, Rodriguez M, Austin E, Andreoli AJ (1978). "Periplasmic localization of nicotinate phosphoribosyltransferase in Escherichia coli." J Bacteriol 1978;133(3);1108-12. PMID: 346557

Basran08: Basran J, Rafice SA, Chauhan N, Efimov I, Cheesman MR, Ghamsari L, Raven EL (2008). "A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase." Biochemistry 47(16);4752-60. PMID: 18370401

Batabyal07: Batabyal D, Yeh SR (2007). "Human tryptophan dioxygenase: a comparison to indoleamine 2,3-dioxygenase." J Am Chem Soc 129(50);15690-701. PMID: 18027945

Bhatia96: Bhatia R, Calvo KC (1996). "The sequencing expression, purification, and steady-state kinetic analysis of quinolinate phosphoribosyl transferase from Escherichia coli." Arch Biochem Biophys 325(2);270-8. PMID: 8561507

Brady75: Brady FO (1975). "Tryptophan 2,3-dioxygenase: a review of the roles of the heme and copper cofactors in catalysis." Bioinorg Chem 5(2);167-82. PMID: 178384

BRENDA, 2014: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Breton00: Breton J, Avanzi N, Magagnin S, Covini N, Magistrelli G, Cozzi L, Isacchi A (2000). "Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase." Eur J Biochem 267(4);1092-9. PMID: 10672018

Brown86: Brown D, Hitchcock MJ, Katz E (1986). "Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus." Can J Microbiol 32(6);465-72. PMID: 2425918

Brown90: Brown OR, Seither RL (1990). "Paraquat toxicity and pyridine nucleotide coenzyme synthesis: a data correction." Free Radic Biol Med 8(2);113-6. PMID: 2139629

Calderone02: Calderone V, Trabucco M, Menin V, Negro A, Zanotti G (2002). "Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli: characterisation of the purified enzyme and its in vitro inhibition by Zn2+." Biochim Biophys Acta 1596(2);283-92. PMID: 12007609

Colabroy05: Colabroy KL, Begley TP (2005). "Tryptophan catabolism: identification and characterization of a new degradative pathway." J Bacteriol 187(22);7866-9. PMID: 16267312

Dahmen67: Dahmen W, Webb B, Preiss J (1967). "The deamido-diphosphopyridine nucleotide and diphosphopyridine nucleotide pyrophosphorylases of Escherichia coli and yeast." Arch Biochem Biophys 1967;120(2);440-50. PMID: 4291828

Emanuelli01: Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G (2001). "Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase." J Biol Chem 276(1);406-12. PMID: 11027696

Emanuelli99: Emanuelli M, Carnevali F, Lorenzi M, Raffaelli N, Amici A, Ruggieri S, Magni G (1999). "Identification and characterization of YLR328W, the Saccharomyces cerevisiae structural gene encoding NMN adenylyltransferase. Expression and characterization of the recombinant enzyme." FEBS Lett 455(1-2);13-7. PMID: 10428462

Foster79: Foster JW, Kinney DM, Moat AG (1979). "Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide." J Bacteriol 137(3);1165-75. PMID: 220211

Foster80: Foster JW, Moat AG (1980). "Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems." Microbiol Rev 44(1);83-105. PMID: 6997723

Foster80a: Foster JW, Baskowsky-Foster AM (1980). "Pyridine nucleotide cycle of Salmonella typhimurium: in vivo recycling of nicotinamide adenine dinucleotide." J Bacteriol 142(3);1032-5. PMID: 6445894

Galeazzi11: Galeazzi L, Bocci P, Amici A, Brunetti L, Ruggieri S, Romine M, Reed S, Osterman AL, Rodionov DA, Sorci L, Raffaelli N (2011). "Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family." J Biol Chem 286(46);40365-75. PMID: 21953451

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Nov 22, 2014, biocyc13.