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: arginine degradation to spermidine, spermidine biosynthesis
|Superclasses:||Biosynthesis → Amines and Polyamines Biosynthesis → Spermidine Biosynthesis|
Some taxa known to possess this pathway include : Arabidopsis thaliana col , Archaea , Bacillus subtilis , Escherichia coli K-12 substr. MG1655 , Eukaryota , Homo sapiens , Saccharomyces cerevisiae , Thermococcus kodakarensis KOD1
The polyamines (the most common of which are putrescine, spermidine, and spermine) are a group of positively charged organic polycations that are involved in any biological processes, including binding to nucleic acids, stabilizing membranes, and stimulating several enzymes [Tabor85, Abraham68, Frydman92, Huang90]. 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]. In the hyperthermophilic archaeon Thermococcus kodakarensis KOD1 both this pathway and pathway spermidine biosynthesis III may lead to the synthesis of longer chain polyamines, with the latter pathway being the main route [Morimoto10].
In Saccharomyces cerevisiae the pathway is realized via the ODC pathway. Spermidine is formed by spermidine synthase which has been characterized through the complementation of a mutant strain (Δspe3). It has been demonstrated that spermidine was absolutely necessary for such mutants to restore wild-type growth and sporulation [HamasakiKatagir97]. The null mutant Δspe3 accumulates putrescine which is an activator of S-adenosylmethionine decarboxylase providing the propylamine moiety necessary to form spermidine [Li01]. The formed other product of the reaction S-adenosyl 3-(methylthio)propylamine is not only a strong competitive inhibitor for the S-adenosylmethionine decarboxylase but is poisonous for yeast when accumulating in Δspe3 mutants [HamasakiKatagir97].
Spermidine is formed by the addition of a propylamine moiety to putrescine, catalyzed by an aminopropyltransferase termed spermidine synthase. The source of the propylamine group is decarboxylated S-adenosyl-L-methionine (S-adenosyl 3-(methylthio)propylamine) which is produced by the action of the pyruvoyl-containing enzyme S-adenosylmethionine decarboxylase. The other product of the aminopropyltransferase reaction is S-methyl-5'-thioadenosine (MTA), which is recycled back to L-methionine.
Superpathways: L-methionine salvage cycle III , L-methionine salvage cycle I (bacteria and plants) , superpathway of polyamine biosynthesis II , superpathway of polyamine biosynthesis I , superpathway of arginine and polyamine biosynthesis
Created 14-Sep-1999 by Pellegrini-Toole A , Marine Biological Laboratory
Revised 31-Oct-2005 by Caspi R , SRI International
Revised 11-Mar-2013 by Foerster H , Boyce Thompson Institute
Last-Curated 11-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
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
HamasakiKatagir97: Hamasaki-Katagiri N, Tabor CW, Tabor H (1997). "Spermidine biosynthesis in Saccharomyces cerevisae: polyamine requirement of a null mutant of the SPE3 gene (spermidine synthase)." Gene 187(1);35-43. PMID: 9073064
Huang90: 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
Li01: Li YF, Hess S, Pannell LK, White Tabor C, Tabor H (2001). "In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 98(19);10578-83. PMID: 11526206
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
Morimoto10: Morimoto N, Fukuda W, Nakajima N, Masuda T, Terui Y, Kanai T, Oshima T, Imanaka T, Fujiwara S (2010). "Dual biosynthesis pathway for longer-chain polyamines in the hyperthermophilic archaeon Thermococcus kodakarensis." J Bacteriol 192(19);4991-5001. PMID: 20675472
Anton87a: Anton DL, Kutny R (1987). "Escherichia coli S-adenosylmethionine decarboxylase. Subunit structure, reductive amination, and NH2-terminal sequences." J Biol Chem 262(6);2817-22. PMID: 3546296
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
Diaz91: Diaz E, Anton DL (1991). "Alkylation of an active-site cysteinyl residue during substrate-dependent inactivation of Escherichia coli S-adenosylmethionine decarboxylase." Biochemistry 1991;30(16);4078-81. PMID: 2018773
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
Ekstrom99: Ekstrom JL, Mathews II, Stanley BA, Pegg AE, Ealick SE (1999). "The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold." Structure Fold Des 7(5);583-95. PMID: 10378277
Friesen98: Friesen H, Tanny JC, Segall J (1998). "Spe3, which encodes spermidine synthase, is required for full repression through NRE(DIT) in Saccharomyces cerevisiae." Genetics 150(1);59-73. PMID: 9725830
Kashiwagi90: Kashiwagi K, Taneja SK, Liu TY, Tabor CW, Tabor H (1990). "Spermidine biosynthesis in Saccharomyces cerevisiae. Biosynthesis and processing of a proenzyme form of S-adenosylmethionine decarboxylase." J Biol Chem 265(36);22321-8. PMID: 2266128
Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493