MetaCyc Pathway: S-adenosyl-L-methionine cycle I
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: S-adenosyl-L-methionine cycle 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: SAM cycle, activated methyl cycle, AMC

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-methionine BiosynthesisL-methionine SalvageS-adenosyl-L-methionine cycle

Some taxa known to possess this pathway include : Aliivibrio fischeri, Bacillus subtilis, Escherichia coli, Salmonella enterica enterica serovar Typhimurium

Expected Taxonomic Range: Archaea, Bacteria

About 20% of the L-methionine pool is used as a building block of proteins. The rest is converted to S-adenosyl-L-methionine (SAM), the major methyl donor in the cell. When SAM donates its methyl group, it is converted to S-adenosyl-L-homocysteine. This molecule can be recycled back to SAM via the S-adenosyl-L-methionine cycle, also known as the activated methyl cycle (AMC).

There are two main variations of this pathway, one found mostly in prokaryotes, while the other is found predominantly, but not exclusively, in eukaryotes. The main difference between the variants is the processing of S-adenosyl-L-homocysteine (SAH), the immediate product of the methylation reactions.

In the first pathway (described in S-adenosyl-L-methionine cycle I) SAH is first hydrolyzed to S-ribosyl-L-homocysteine by the MTA/SAH nucleosidase, followed by conversion to L-homocysteine by S-ribosylhomocysteine lyase. In the second pathway, which is described in S-adenosyl-L-methionine cycle II, SAH is hydrolyzed to L-homocysteine in a single step, catalyzed by S-adenosylhomocysteine hydrolase.

The cycle continues with the methylation of L-homocysteine to L-methionine using a methyl group from a methylated folate. In some organisms, including Homo sapiens, this reaction is catalyzed by a cobalamin-dependent methionine synthase (EC In other organisms, such as Bacillus subtilis, the reaction is catalyzed by a cobalamin-independent methionine synthase (EC Yet some organisms, such as Escherichia coli and Corynebacterium glutamicum, have both enzymes, as described in the pathway L-methionine biosynthesis III. In Escherichia coli the reaction catalyzed by the B12-dependent enzyme is more than 100-fold faster than the reaction catalyzed by the B12-independent isoenzyme [Rodionov04].

Finally, the cycle is completed with the regeneration of SAM by S-adenosylmethionine synthetase.

Subpathways: S-adenosyl-L-methionine biosynthesis

Variants: S-adenosyl-L-methionine cycle II

Unification Links: EcoCyc:PWY-6151

Created 09-Mar-2009 by Caspi R, SRI International


Rezzonico08: Rezzonico F, Duffy B (2008). "Lack of genomic evidence of AI-2 receptors suggests a non-quorum sensing role for luxS in most bacteria." BMC Microbiol 8;154. PMID: 18803868

Rodionov04: Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS (2004). "Comparative genomics of the methionine metabolism in Gram-positive bacteria: a variety of regulatory systems." Nucleic Acids Res 32(11);3340-53. PMID: 15215334

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

Allart98: Allart B, Gatel M, Guillerm D, Guillerm G (1998). "The catalytic mechanism of adenosylhomocysteine/methylthioadenosine nucleosidase from Escherichia coli--chemical evidence for a transition state with a substantial oxocarbenium character." Eur J Biochem 256(1);155-62. PMID: 9746359

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

Cabrero87: Cabrero C, Puerta J, Alemany S (1987). "Purification and comparison of two forms of S-adenosyl-L-methionine synthetase from rat liver." Eur J Biochem 170(1-2);299-304. PMID: 3121322

Cantoni51: Cantoni, G. L. (1951). "Methylation of nicotinamide with a soluble enzyme system from rat liver." J. Biol. Chem. 189: 203 - 216.

Capitanio03: Capitanio N, Capitanio G, De Nitto E, Boffoli D, Papa S (2003). "Proton transfer reactions associated with the reaction of the fully reduced, purified cytochrome C oxidase with molecular oxygen and ferricyanide." Biochemistry 42(16);4607-12. PMID: 12705823

Chattopadhyay91: Chattopadhyay MK, Ghosh AK, Sengupta S (1991). "Control of methionine biosynthesis in Escherichia coli K12: a closer study with analogue-resistant mutants." J Gen Microbiol 137(3);685-91. PMID: 2033383

Chiang77: Chiang PK, Cantoni GL (1977). "Activation of methionine for transmethylation. Purification of the S-adenosylmethionine synthetase of bakers' yeast and its separation into two forms." J Biol Chem 1977;252(13);4506-13. PMID: 194884

Chou72: Chou TC, Talalay P (1972). "The mechanism of S-adenosyl-L-methionine synthesis by purified preparations of bakers' yeast." Biochemistry 1972;11(6);1065-73. PMID: 4552214

Cornell98: Cornell KA, Riscoe MK (1998). "Cloning and expression of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase: identification of the pfs gene product." Biochim Biophys Acta 1396(1);8-14. PMID: 9524204

Csaikl86: Csaikl U, Csaikl F (1986). "Molecular cloning and characterization of the MET6 gene of Saccharomyces cerevisiae." Gene 46(2-3);207-14. PMID: 3542720

Della85: Della Ragione F, Porcelli M, Carteni-Farina M, Zappia V, Pegg AE (1985). "Escherichia coli S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase. Purification, substrate specificity and mechanism of action." Biochem J 232(2);335-41. PMID: 3911944

Eichel95: Eichel J, Gonzalez JC, Hotze M, Matthews RG, Schroder J (1995). "Vitamin-B12-independent methionine synthase from a higher plant (Catharanthus roseus). Molecular characterization, regulation, heterologous expression, and enzyme properties." Eur J Biochem 230(3);1053-8. PMID: 7601135

Farrar10: Farrar CE, Siu KK, Howell PL, Jarrett JT (2010). "Biotin synthase exhibits burst kinetics and multiple turnovers in the absence of inhibition by products and product-related biomolecules." Biochemistry 49(46);9985-96. PMID: 20961145

Ferro76: Ferro AJ, Barrett A, Shapiro SK (1976). "Kinetic properties and the effect of substrate analogues on 5'-methylthioadenosine nucleosidase from Escherichia coli." Biochim Biophys Acta 438(2);487-94. PMID: 782530

Gakiere99: Gakiere B, Job D, Douce R, Ravanel S "Characterization of the cDNA and Gene for a Cytosolic Cobalamin-Independent Methionine Synthase in Arabidopsis thaliana (Accession No. U97200). (PGR99-115)." Plant Physiol. (1999), 120, 1206.

Gopishetty09: Gopishetty B, Zhu J, Rajan R, Sobczak AJ, Wnuk SF, Bell CE, Pei D (2009). "Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues." J Am Chem Soc 131(3);1243-50. PMID: 19099445

Greene73: Greene RC, Hunter JS, Coch EH (1973). "Properties of metK mutants of Escherichia coli K-12." J Bacteriol 115(1);57-67. PMID: 4577753

Grundy02: Grundy,F.J., Henkin,T.M. (2002). "Synthesis of serine, glycine, cysteine, and methionine." in Sonenshein,A.L., Hoch,J.A. and Losick,R. (eds), Bacillus subtilis and its Relatives: From Genes to Cells. American Society for Microbiology, Washington, DC, pp. 245254.

Guest64: Guest JR, Friedman S, Foster MA, Tejerina G, Woods DD (1964). "Transfer of the methyl group from N5-methyltetrahydrofolates to homocysteine in Escherichia coli." Biochem J 92(3);497-504. PMID: 5319972

Gutierrez09: Gutierrez JA, Crowder T, Rinaldo-Matthis A, Ho MC, Almo SC, Schramm VL (2009). "Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing." Nat Chem Biol 5(4):251-7. PMID: 19270684

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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
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