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MetaCyc Pathway: inosine-5'-phosphate biosynthesis II
Inferred from experiment

Enzyme View:

Pathway diagram: inosine-5'-phosphate biosynthesis II

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: IMP biosynthesis II

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisPurine Nucleotide BiosynthesisPurine Nucleotides De Novo BiosynthesisPurine Riboucleotides De Novo BiosynthesisInosine-5'-phosphate Biosynthesis

Some taxa known to possess this pathway include : Homo sapiens, Saccharomyces cerevisiae

Expected Taxonomic Range: Eukaryota

De novo biosynthesis of purines starts with the synthesis of IMP, which can be converted to all other purines.

In the bacterium Escherichia coli IMP is synthesized from 5-amino-1-(5-phospho-β-D-ribosyl)imidazole in 6 steps (see inosine-5'-phosphate biosynthesis I). In eukaryotes the pathway consists of only 5 steps. The difference is in the first two steps, which are replaced in eukaryotes with a single reaction.

The first 3 steps of this pathway are catalyzed in the yeast Saccharomyces cerevisiae by individual enzymes, while the last two steps are catalyzed by a single multifunctional enzyme|. Saccharomyces cerevisiae possesses two isozymes of the multifunctional enzyme, encoded by the ADE16 and ADE17 genes. While these isozymes are indistinguishable with respect to activity, cellular location and subunit structure, they do differ in expression levels, and Ade17 is the major isozyme, accounting for approximately 90% activity [Tibbetts00, Tibbetts97].

Superpathways: superpathway of purine nucleotides de novo biosynthesis I

Variants: inosine-5'-phosphate biosynthesis I, inosine-5'-phosphate biosynthesis III

Created 13-Jan-2009 by Caspi R, SRI International


Firestine98: Firestine SM, Misialek S, Toffaletti DL, Klem TJ, Perfect JR, Davisson VJ (1998). "Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis." Arch Biochem Biophys 351(1);123-34. PMID: 9500840

Tibbetts00: Tibbetts AS, Appling DR (2000). "Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase isozymes from Saccharomyces cerevisiae." J Biol Chem 2000;275(27);20920-7. PMID: 10877846

Tibbetts97: Tibbetts AS, Appling DR (1997). "Saccharomyces cerevisiae expresses two genes encoding isozymes of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase." Arch Biochem Biophys 1997;340(2);195-200. PMID: 9143321

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

Aiba89: Aiba A, Mizobuchi K (1989). "Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli." J Biol Chem 1989;264(35);21239-46. PMID: 2687276

Alenin92: Alenin VV, Ostanin KV, Kostikova TR, Domkin VD, Zubova VA, Smirnov MN (1992). "[Substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase) from Saccharomyces cerevisiae yeast]." Biokhimiia 1992;57(6);845-55. PMID: 1420588

Bulock02: Bulock KG, Beardsley GP, Anderson KS (2002). "The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling." J Biol Chem 277(25);22168-74. PMID: 11948179

Cheong04: Cheong CG, Wolan DW, Greasley SE, Horton PA, Beardsley GP, Wilson IA (2004). "Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates." J Biol Chem 279(17);18034-45. PMID: 14966129

Fon93: Fon EA, Demczuk S, Delattre O, Thomas G, Rouleau GA (1993). "Mapping of the human adenylosuccinate lyase (ADSL) gene to chromosome 22q13.1-->q13.2." Cytogenet Cell Genet 64(3-4);201-3. PMID: 8404037

Graupner02: Graupner M, Xu H, White RH (2002). "New class of IMP cyclohydrolases in Methanococcus jannaschii." J Bacteriol 184(5);1471-3. PMID: 11844782

He92: He B, Smith JM, Zalkin H (1992). "Escherichia coli purB gene: cloning, nucleotide sequence, and regulation by purR." J Bacteriol 1992;174(1);130-6. PMID: 1729205

Kmoch00: Kmoch S, Hartmannova H, Stiburkova B, Krijt J, Zikanova M, Sebesta I (2000). "Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients." Hum Mol Genet 9(10);1501-13. PMID: 10888601

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee07c: Lee P, Colman RF (2007). "Expression, purification, and characterization of stable, recombinant human adenylosuccinate lyase." Protein Expr Purif 51(2);227-34. PMID: 16973378

Levdikov98: Levdikov VM, Barynin VV, Grebenko AI, Melik-Adamyan WR, Lamzin VS, Wilson KS (1998). "The structure of SAICAR synthase: an enzyme in the de novo pathway of purine nucleotide biosynthesis." Structure 1998;6(3);363-76. PMID: 9551557

Li07c: Li SX, Tong YP, Xie XC, Wang QH, Zhou HN, Han Y, Zhang ZY, Gao W, Li SG, Zhang XC, Bi RC (2007). "Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis." J Mol Biol 366(5);1603-14. PMID: 17224163

Marie04: Marie S, Heron B, Bitoun P, Timmerman T, Van Den Berghe G, Vincent MF (2004). "AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC." Am J Hum Genet 74(6);1276-81. PMID: 15114530

Meyer92: Meyer E, Leonard NJ, Bhat B, Stubbe J, Smith JM (1992). "Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway." Biochemistry 1992;31(21);5022-32. PMID: 1534690

Minet90: Minet M, Lacroute F (1990). "Cloning and sequencing of a human cDNA coding for a multifunctional polypeptide of the purine pathway by complementation of the ade2-101 mutant in Saccharomyces cerevisiae." Curr Genet 18(4);287-91. PMID: 2253271

Nelson05: Nelson SW, Binkowski DJ, Honzatko RB, Fromm HJ (2005). "Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase." Biochemistry 44(2);766-74. PMID: 15641804

Ostanin89: Ostanin KV, Alenin VV, Domkin VD, Smirnov MN (1989). "[Isolation and properties of phosphoribosyl-aminoimidazole-succinocarboxyamide-synthestase from Saccharomyces cerevisiae yeasts]." Biokhimiia 1989;54(8);1265-73. PMID: 2684279

Porter83: Porter DJ, Rudie NG, Bright HJ (1983). "Nitro analogs of substrates for adenylosuccinate synthetase and adenylosuccinate lyase." Arch Biochem Biophys 1983;225(1);157-63. PMID: 6351751

Ray12: Ray SP, Deaton MK, Capodagli GC, Calkins LA, Sawle L, Ghosh K, Patterson D, Pegan SD (2012). "Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation." Biochemistry 51(33);6701-13. PMID: 22812634

Rayl96a: Rayl EA, Moroson BA, Beardsley GP (1996). "The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping." J Biol Chem 271(4);2225-33. PMID: 8567683

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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 Pathway Tools version 19.5 (software by SRI International) on Thu Apr 28, 2016, biocyc14.