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:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Purine Nucleotide Biosynthesis → Purine Nucleotides De Novo Biosynthesis → Purine Riboucleotides De Novo Biosynthesis → Inosine-5'-phosphate Biosynthesis|
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
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
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
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
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
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
Rayl96: 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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