If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: ODC pathway
|Superclasses:||Biosynthesis → Amines and Polyamines Biosynthesis → Putrescine Biosynthesis|
Pathway Summary from MetaCyc:
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, Huang90a]. 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].
Pathway Evidence Glyph:
Created in MetaCyc 10-Oct-2005 by Caspi R , SRI International
Revised in MetaCyc 09-Mar-2013 by Foerster H , Boyce Thompson Institute
Imported from MetaCyc 08-Aug-2014 by Subhraveti P , 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
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
Huang90a: 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
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