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: ODC pathway
|Superclasses:||Biosynthesis → Amines and Polyamines Biosynthesis → Putrescine Biosynthesis|
The polyamines (the most common of which are putrescine, spermidine, and spermine) are a group of positively charged organic polycations that are involved in many biological processes, including binding to nucleic acids, stabilizing membranes, and stimulating several enzymes [Tabor85, Abraham68, Frydman92, Huang90b]. While it is clear that polyamines are essential for normal cell growth, we still do not fully understand their specific molecular functions in vivo [Tabor85]. putrescine and spermidine are found in all life forms, and spermine is found mostly in eukaryotes.
putrescine can be formed either directly from L-ornithine by ornithine decarboxylase (ODC) (see putrescine biosynthesis III) or indirectly from L-arginine by arginine decarboxylase (ADC) (see putrescine biosynthesis I and putrescine biosynthesis II). While the ODC pathway was considered the only mammalian pathway for polyamine biosynthesis, recently the presence of the ADC pathway in mammals has been demonstrated [Mistry02, Zhu04]. In higher plants the presence of both pathways has been known for some time [Galston90]. In bacteria, both pathways are common, and are often found side by side in the same organism [Tabor85].
About This Pathway
In the ODC pathway putrescine is generated in a single reaction from L-ornithine by the enzyme ornithine decarboxylase. L-ornithine can be decarboxylated into putrescine for two purposes - either anabolically, for the generation of putrescine as a polyamine on its own, or as a precursor of spermidine, or catabolically, as a carbon and nitrogen source. Catabolic L-ornithine degradation is illustrated in the pathway superpathway of ornithine degradation.
Enteric bacteria possess two forms of ornithine decarboxylase, a biosynthetic (or constitutive) form (for example, ornithine decarboxylase, biosynthetic), apparently present in all strains of Escherichia coli, and a biodegradative (or inducible) form (for example, ornithine decarboxylase, degradative), which is present in only some strains of Escherichia coli [Tabor85, Kashiwagi91]. Other organisms, such as Pseudomonas aeruginosa appear to have only a single ornithine decarboxylase, which is regulated in a complex manner to ensure proper expression for both polyamine biosynthesis and catabolism.
Biosynthetic ornithine decarboxylase is inhibited by both putrescine and spermidine, and is activated by GTP and other nucleotides [Holtta74]. A synthetic compound, difluoromethylornithine, is a very potent mechanism-based (suicide) irreversible inhibitor of most ornithine decarboxylases, which has attracted much attention [Sjoerdsma84]. Interestingly, the Escherichia coli K-12 enzyme is completely immune to this inhibitor [Kallio81].
The formation of putrescine by the catalytic action of ornithine decarboxylase in Saccharomyces cerevisiae has been determined utilizing null mutants of the encoding gene (Δspe1) which are unable to grow but can be rescued by addition of polyamines to the growth medium [Balasundaram94, Schwartz95]. The regulation of the ornithine decarboxylase activity in yeast has been proposed to occur via an antizyme-like mechanism which controls the degradation of the enzyme [Gupta01].
Abraham68: Abraham KA (1968). "Studies on DNA-dependent RNA polymerase from Escherichia coli. 1. The mechanism of polyamine induced stimulation of enzyme activity." Eur J Biochem 5(1);143-6. PMID: 4873311
Balasundaram94: Balasundaram D, Xie QW, Tabor CW, Tabor H (1994). "The presence of an active S-adenosylmethionine decarboxylase gene increases the growth defect observed in Saccharomyces cerevisiae mutants unable to synthesize putrescine, spermidine, and spermine." J Bacteriol 176(20);6407-9. PMID: 7929015
Frydman92: Frydman L, Rossomando PC, Frydman V, Fernandez CO, Frydman B, Samejima K (1992). "Interactions between natural polyamines and tRNA: an 15N NMR analysis." Proc Natl Acad Sci U S A 89(19);9186-90. PMID: 1409623
Gupta01: Gupta R, Hamasaki-Katagiri N, White Tabor C, Tabor H (2001). "Effect of spermidine on the in vivo degradation of ornithine decarboxylase in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 98(19);10620-3. PMID: 11535806
Huang90b: Huang SC, Panagiotidis CA, Canellakis ES (1990). "Transcriptional effects of polyamines on ribosomal proteins and on polyamine-synthesizing enzymes in Escherichia coli." Proc Natl Acad Sci U S A 87(9);3464-8. PMID: 2185470
Kallio81: Kallio A, McCann PP (1981). "Difluoromethylornithine irreversibly inactivates ornithine decarboxylase of Pseudomonas aeruginosa, but does not inhibit the enzymes of Escherichia coli." Biochem J 200(1);69-75. PMID: 6800359
Kashiwagi91: Kashiwagi K, Suzuki T, Suzuki F, Furuchi T, Kobayashi H, Igarashi K (1991). "Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome." J Biol Chem 1991;266(31);20922-7. PMID: 1939141
Mistry02: Mistry SK, Burwell TJ, Chambers RM, Rudolph-Owen L, Spaltmann F, Cook WJ, Morris SM (2002). "Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus." Am J Physiol Gastrointest Liver Physiol 282(2);G375-81. PMID: 11804860
Schwartz95: Schwartz B, Hittelman A, Daneshvar L, Basu HS, Marton LJ, Feuerstein BG (1995). "A new model for disruption of the ornithine decarboxylase gene, SPE1, in Saccharomyces cerevisiae exhibits growth arrest and genetic instability at the MAT locus." Biochem J 312 ( Pt 1);83-90. PMID: 7492339
Alabadi98: Alabadi D, Carbonell J (1998). "Expression of ornithine decarboxylase is transiently increased by pollination, 2,4-dichlorophenoxyacetic acid, and gibberellic acid in tomato ovaries." Plant Physiol 118(1);323-8. PMID: 9733552
Almrud00: Almrud JJ, Oliveira MA, Kern AD, Grishin NV, Phillips MA, Hackert ML (2000). "Crystal structure of human ornithine decarboxylase at 2.1 A resolution: structural insights to antizyme binding." J Mol Biol 295(1);7-16. PMID: 10623504
Anagnostopoulos96: Anagnostopoulos CG, Kyriakidis DA (1996). "Regulation of the Escherichia coli biosynthetic ornithine decarboxylase activity by phosphorylation and nucleotides." Biochim Biophys Acta 1297(2);228-34. PMID: 8917626
Applebaum75: Applebaum D, Sabo DL, Fischer EH, Morris DR (1975). "Biodegradative ornithine decarboxylase of Escherichia coli. Purification, properties, and pyridoxal 5'-phosphate binding site." Biochemistry 1975;14(16);3675-81. PMID: 240388
Canellakis93: Canellakis ES, Paterakis AA, Huang SC, Panagiotidis CA, Kyriakidis DA (1993). "Identification, cloning, and nucleotide sequencing of the ornithine decarboxylase antizyme gene of Escherichia coli." Proc Natl Acad Sci U S A 90(15);7129-33. PMID: 8346225
CunninghamRundl75: Cunningham-Rundles S, Maas WK (1975). "Isolation, characterization, and mapping of Escherichia coli mutants blocked in the synthesis of ornithine decarboxylase." J Bacteriol 124(2);791-9. PMID: 1102531
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Filippou07: Filippou PS, Lioliou EE, Panagiotidis CA, Athanassopoulos CM, Garnelis T, Papaioannou D, Kyriakidis DA (2007). "Effect of polyamines and synthetic polyamine-analogues on the expression of antizyme (AtoC) and its regulatory genes." BMC Biochem 8;1. PMID: 17224065
Holtta72: Holtta E, Janne J, Pispa J (1972). "Ornithine decarboxylase from Escherichia coli: stimulation of the enzyme activity by nucleotides." Biochem Biophys Res Commun 47(5);1165-71. PMID: 4555250
Hu03a: Hu HY, Liu XX, Jiang CY, Zhang Y, Bian JF, Lu Y, Geng Z, Liu SL, Liu CH, Wang XM, Wang W (2003). "Cloning and expression of ornithine decarboxylase gene from human colorectal carcinoma." World J Gastroenterol 9(4);714-6. PMID: 12679917
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