If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: SAM cycle, activated methyl cycle, AMC
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Individual Amino Acids Biosynthesis → Methionine Biosynthesis → Methionine Salvage → S-adenosyl-L-methionine cycle|
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.
About this pathway
In this pathway, SAH is first hydrolyzed to S-ribosyl-L-homocysteine by 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase, followed by conversion to L-homocysteine by S-ribosylhomocysteine lyase. The cycle continues with the methylation of L-homocysteine to L-methionine using a methyl group from a methylated folate. Finally, the cycle is completed with the regeneration of SAM by methionine adenosyltransferase.
The metabolites of this pathway have been quantitatively profiled as a function of growth in wild-type and mtn or luxS mutant E. coli [Halliday10].
Subpathways: S-adenosyl-L-methionine biosynthesis
Halliday10: Halliday NM, Hardie KR, Williams P, Winzer K, Barrett DA (2010). "Quantitative liquid chromatography-tandem mass spectrometry profiling of activated methyl cycle metabolites involved in LuxS-dependent quorum sensing in Escherichia coli." Anal Biochem 403(1-2);20-9. PMID: 20417170
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
Arifuzzaman et al., 2006: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
Banerjee89: Banerjee RV, Johnston NL, Sobeski JK, Datta P, Matthews RG (1989). "Cloning and sequence analysis of the Escherichia coli metH gene encoding cobalamin-dependent methionine synthase and isolation of a tryptic fragment containing the cobalamin-binding domain." J Biol Chem 1989;264(23);13888-95. PMID: 2668277
Banerjee90: Banerjee RV, Frasca V, Ballou DP, Matthews RG (1990). "Participation of cob(I) alamin in the reaction catalyzed by methionine synthase from Escherichia coli: a steady-state and rapid reaction kinetic analysis." Biochemistry 1990;29(50);11101-9. PMID: 2271698
Boysen10: Boysen A, Moller-Jensen J, Kallipolitis B, Valentin-Hansen P, Overgaard M (2010). "Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli." J Biol Chem 285(14);10690-702. PMID: 20075074
Brito13: Brito PH, Rocha EP, Xavier KB, Gordo I (2013). "Natural genome diversity of AI-2 quorum sensing in Escherichia coli: conserved signal production but labile signal reception." Genome Biol Evol 5(1);16-30. PMID: 23246794
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
Chu85: Chu J, Shoeman R, Hart J, Coleman T, Mazaitis A, Kelker N, Brot N, Weissbach H (1985). "Cloning and expression of the metE gene in Escherichia coli." Arch Biochem Biophys 239(2);467-74. PMID: 2988449
Clinch12: Clinch K, Evans GB, Frohlich RF, Gulab SA, Gutierrez JA, Mason JM, Schramm VL, Tyler PC, Woolhouse AD (2012). "Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics." Bioorg Med Chem 20(17);5181-7. PMID: 22854195
Cornell96: Cornell KA, Swarts WE, Barry RD, Riscoe MK (1996). "Characterization of recombinant Eschericha coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity." Biochem Biophys Res Commun 228(3);724-32. PMID: 8941345
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
Daniels92: Daniels DL, Plunkett G, Burland V, Blattner FR (1992). "Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes." Science 1992;257(5071);771-8. PMID: 1379743
Datta08: Datta S, Koutmos M, Pattridge KA, Ludwig ML, Matthews RG (2008). "A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor." Proc Natl Acad Sci U S A 105(11);4115-20. PMID: 18332423
DeLisa01: DeLisa MP, Wu CF, Wang L, Valdes JJ, Bentley WE (2001). "DNA microarray-based identification of genes controlled by autoinducer 2-stimulated quorum sensing in Escherichia coli." J Bacteriol 183(18);5239-47. PMID: 11514505
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
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