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MetaCyc Pathway: spermidine biosynthesis I
Inferred from experiment

Enzyme View:

Pathway diagram: spermidine biosynthesis I

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: BiosynthesisAmines and Polyamines BiosynthesisSpermidine 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, Solanum tuberosum, Thermococcus kodakarensis KOD1

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

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 [Li01c]. 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

Variants: spermidine biosynthesis II, spermidine biosynthesis III


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

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

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

Li01c: 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

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

Anton87: Anton DL, Kutny R (1987). "Mechanism of substrate inactivation of Escherichia coli S-adenosylmethionine decarboxylase." Biochemistry 26(20);6444-7. PMID: 3322380

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

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

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

Bowman73: Bowman WH, Tabor CW, Tabor H (1973). "Spermidine biosynthesis. Purification and properties of propylamine transferase from Escherichia coli." J Biol Chem 1973;248(7);2480-6. PMID: 4572733

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

ECOSAL: EcoSal "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

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

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."

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

Kajander89: Kajander EO, Kauppinen LI, Pajula RL, Karkola K, Eloranta TO (1989). "Purification and partial characterization of human polyamine synthases." Biochem J 259(3);879-86. PMID: 2730590

Kashiwagi88: Kashiwagi K, Igarashi K (1988). "Adjustment of polyamine contents in Escherichia coli." J Bacteriol 170(7);3131-5. PMID: 3290196

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

Kolar52: Kolar, V (1952). "[Experiences with the treatment of leukemia.]." Bratisl Lek Listy 7(2);38-42. PMID: 14918534

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee12b: Lee MJ, Yang YT, Lin V, Huang H (2012). "Site-Directed Mutations of the Gatekeeping Loop Region Affect the Activity of Escherichia coli Spermidine Synthase." Mol Biotechnol. PMID: 23001854

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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 Mon May 2, 2016, biocyc13.