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MetaCyc Pathway: putrescine biosynthesis III
Inferred from experiment

Enzyme View:

Pathway diagram: putrescine biosynthesis III

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: BiosynthesisAmines and Polyamines BiosynthesisPutrescine Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Homo sapiens, Nicotiana tabacum, Pseudomonas aeruginosa, Saccharomyces cerevisiae

Expected Taxonomic Range: Bacteria , Eukaryota

General Backround

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, Huang90c]. 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].

Superpathways: superpathway of polyamine biosynthesis II, superpathway of polyamine biosynthesis I, superpathway of arginine and polyamine biosynthesis

Variants: putrescine biosynthesis I, putrescine biosynthesis II, putrescine biosynthesis IV

Unification Links: AraCyc:PWY-46, EcoCyc:PWY-46

Created 10-Oct-2005 by Caspi R, SRI International
Revised 09-Mar-2013 by Foerster H, Boyce Thompson Institute
Last-Curated 04-Apr-2011 by Fulcher CA, SRI International


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

Galston90: Galston AW, Sawhney RK (1990). "Polyamines in plant physiology." Plant Physiol 94(2);406-10. PMID: 11537482

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

Holtta74: Holtta E, Janne J, Pispa J (1974). "The regulation of polyamine synthesis during the stringent control in Escherichia coli." Biochem Biophys Res Commun 59(3);1104-11. PMID: 4370496

Huang90c: 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

Morris70: Morris DR, Jorstad CM (1970). "Isolation of conditionally putrescine-deficient mutants of Escherichia coli." J Bacteriol 101(3);731-7. PMID: 4908781

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

Sjoerdsma84: Sjoerdsma A, Schechter PJ (1984). "Chemotherapeutic implications of polyamine biosynthesis inhibition." Clin Pharmacol Ther 35(3);287-300. PMID: 6421528

Tabor85: Tabor CW, Tabor H (1985). "Polyamines in microorganisms." Microbiol Rev 1985;49(1);81-99. PMID: 3157043

Zhu04: Zhu MY, Iyo A, Piletz JE, Regunathan S (2004). "Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine." Biochim Biophys Acta 1670(2);156-64. PMID: 14738999

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

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

Applebaum77: Applebaum DM, Dunlap JC, Morris DR (1977). "Comparison of the biosynthetic and biodegradative ornithine decarboxylases of Escherichia coli." Biochemistry 1977;16(8);1580-4. PMID: 15587

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Cohn80: Cohn MS, Tabor CW, Tabor H (1980). "Regulatory mutations affecting ornithine decarboxylase activity in Saccharomyces cerevisiae." J Bacteriol 142(3);791-9. PMID: 6991493

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

Fitzgerald89: Fitzgerald MC, Flanagan MA (1989). "Characterization and sequence analysis of the human ornithine decarboxylase gene." DNA 8(9);623-34. PMID: 2693021

Fonzi87: Fonzi WA, Sypherd PS (1987). "The gene and the primary structure of ornithine decarboxylase from Saccharomyces cerevisiae." J Biol Chem 262(21);10127-33. PMID: 3038869

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

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

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Ivanov98: Ivanov IP, Gesteland RF, Atkins JF (1998). "Does antizyme exist in Escherichia coli?." Mol Microbiol 29(6);1521-2. PMID: 9781887

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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 Fri Apr 29, 2016, biocyc13.