If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|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, 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].
There are two flavors of the ADC pathway. In both cases L-arginine is first converted to agmatine by a biosynthetic arginine decarboxylase. However, in enterobacteria and mycobacteria agmatine is converted directly to putrescine by the enzyme agmatinase (this pathway), while in higher plants, Pseudomonas spp., Aeromonas spp., and lactic bacteria, agmatine is first hydrolyzed by agmatine deiminase into N-carbamoylputrescine and ammonia, and putrescine is formed by removal of the ureido group from N-carbamoylputrescine by the enzyme N-carbamoylputrescine amidohydrolase (see pathway putrescine biosynthesis II).
About This Pathway
This pathway was studied mostly in enterobacteria, but it was also found in the mycobacteria Mycobacterium phlei and Mycobacterium smegmatis [Zeller54] and in the Gram positive bacterium Bacillus subtilis [Sekowska98]. While Escherichia coli K-12 possesses both an ODC and an ADC pathways, in Bacillus subtilis this is the only putrescine biosynthetic pathway. Remarkably, even though spermidine is only synthesized in Bacillus subtilis via putrescine, no intracellular putrescine was found in this organism [Sekowska98].
It should be mentioned that in some organisms, including Escherichia coli K-12, this pathway can also operate in a catabolic manner [Shaibe85a], catalyzing the degradation of L-arginine through putrescine into succinate (see arginine degradation III (arginine decarboxylase/agmatinase pathway)). However, the main catabolic arginine pathway in these bacteria is the succinyltransferase pathway (arginine degradation II (AST pathway)). Interestingly, unlike Escherichia coli K-12, wild-type E. coli strains are unable to use L-arginine as a carbon source, even though they can use it as a nitrogen source [Cunin86].
Escherichia coli K-12 has two forms of the enzyme arginine decarboxylase: a constitutive, biosynthetic form, encoded by the speA gene, and an inducible catabolic form, encoded by the adiA gene. When the cataolic form is not expressed, the pathway operates only in an anabolic manner, catalyzing the biosynthesis of putrescine, which is used by the bacteria either directly or as a precursor for the biosynthesis of other polyamines (see superpathway of polyamine biosynthesis I). However, when the cells are grown in an arginine-rich medium, especially if the medium is acidic and conditions are semi-anaerobic, the catabolic arginine decarboxylase is expressed, and the pathway operates in a catabolic manner, feeding putrescine via 4-aminobutanoate and succinate into the TCA cycle I (prokaryotic) [Tabor85].
Variants: putrescine biosynthesis III
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
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
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
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
Shaibe85a: Shaibe E, Metzer E, Halpern YS (1985). "Metabolic pathway for the utilization of L-arginine, L-ornithine, agmatine, and putrescine as nitrogen sources in Escherichia coli K-12." J Bacteriol 163(3);933-7. PMID: 3897201
Andrell09: Andrell J, Hicks MG, Palmer T, Carpenter EP, Iwata S, Maher MJ (2009). "Crystal structure of the acid-induced arginine decarboxylase from Escherichia coli: reversible decamer assembly controls enzyme activity." Biochemistry 48(18);3915-27. PMID: 19298070
Bitonti87: Bitonti AJ, Casara PJ, McCann PP, Bey P (1987). "Catalytic irreversible inhibition of bacterial and plant arginine decarboxylase activities by novel substrate and product analogues." Biochem J 1987;242(1);69-74. PMID: 3297044
Blethen68: Blethen SL, Boeker EA, Snell EE (1968). "Argenine decarboxylase from Escherichia coli. I. Purification and specificity for substrates and coenzyme." J Biol Chem 1968;243(8);1671-7. PMID: 4870599
Boyle84: Boyle SM, Markham GD, Hafner EW, Wright JM, Tabor H, Tabor CW (1984). "Expression of the cloned genes encoding the putrescine biosynthetic enzymes and methionine adenosyltransferase of Escherichia coli (speA, speB, speC and metK)." Gene 30(1-3);129-36. PMID: 6392022
Carvajal04: Carvajal N, Orellana MS, Salas M, Enriquez P, Alarcon R, Uribe E, Lopez V (2004). "Kinetic studies and site-directed mutagenesis of Escherichia coli agmatinase. A role for Glu274 in binding and correct positioning of the substrate guanidinium group." Arch Biochem Biophys 430(2);185-90. PMID: 15369817
Carvajal99: Carvajal N, Lopez V, Salas M, Uribe E, Herrera P, Cerpa J (1999). "Manganese is essential for catalytic activity of Escherichia coli agmatinase." Biochem Biophys Res Commun 258(3);808-11. PMID: 10329468
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
Moore90: Moore RC, Boyle SM (1990). "Nucleotide sequence and analysis of the speA gene encoding biosynthetic arginine decarboxylase in Escherichia coli." J Bacteriol 1990;172(8);4631-40. PMID: 2198270
Moore91: Moore RC, Boyle SM (1991). "Cyclic AMP inhibits and putrescine represses expression of the speA gene encoding biosynthetic arginine decarboxylase in Escherichia coli." J Bacteriol 1991;173(12);3615-21. PMID: 1646785
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493