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.
|Superclasses:||Degradation/Utilization/Assimilation → Nucleosides and Nucleotides Degradation → S-methyl-5'-thioadenosine Degradation|
S-methyl-5'-thioadenosine (MTA) is a side product in the biosynthesis of several important compounds. An important case is polyamine synthesis, where L-methionine is consumed through the utilization of S-adenosyl-L-methionine (SAM) in a reaction that releases MTA (see the pathway superpathway of polyamine biosynthesis II). MTA is a strong inhibitor of polyamine biosynthesis and transmethylation reactions, and its concentration needs to be tightly regulated.
To ensure that the pathways that produce MTA as a byproduct are not blocked, the organism must remove this compound. The most common way of achieving it is through the methionine salvage pathway, in which MTA is recycled through a series of reactions back to AMP and L-methionine. While the methionine salvage pathway is widely conserved, its initial steps, converting MTA to S-methyl-5-thio-α-D-ribose 1-phosphate, differ among microorganisms and plants (such as the bacteria Klebsiella pneumoniae [Cornell96] and Bacillus subtilis [Sekowska02]), protozoans (such as Giardia intestinalis and Plasmodium falciparum [Riscoe88]) and mammalian cells. The different routes employed by these organisms are described in the different pathways under S-methyl-5'-thioadenosine Degradation.
About This Pathway
This pathway is found mostly in bacteria and plants. In it MTA is degraded to S-methyl-5-thio-α-D-ribose 1-phosphate (MTRP) in two steps; MTA is initially cleaved to adenine and S-methyl-5-thio-D-ribose (MTR) by 5'-methylthioadenosine nucleosidase, followed by phosphorylation of MTR to MTRP by 5'-methylthioribose kinase.
Cornell96: Cornell KA, Winter RW, Tower PA, Riscoe MK (1996). "Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae." Biochem J 1996;317 ( Pt 1);285-90. PMID: 8694776
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
Cornell96a: 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
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
Gianotti90: Gianotti AJ, Tower PA, Sheley JH, Conte PA, Spiro C, Ferro AJ, Fitchen JH, Riscoe MK (1990). "Selective killing of Klebsiella pneumoniae by 5-trifluoromethylthioribose. Chemotherapeutic exploitation of the enzyme 5-methylthioribose kinase." J Biol Chem 1990;265(2);831-7. PMID: 2153115
Guranowski81: Guranowski AB, Chiang PK, Cantoni GL (1981). "5'-Methylthioadenosine nucleosidase. Purification and characterization of the enzyme from Lupinus luteus seeds." Eur J Biochem 114(2);293-9. PMID: 6783408
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
Lee05b: Lee JE, Luong W, Huang DJ, Cornell KA, Riscoe MK, Howell PL (2005). "Mutational analysis of a nucleosidase involved in quorum-sensing autoinducer-2 biosynthesis." Biochemistry 44(33);11049-57. PMID: 16101288
Li11: Li X, Apel D, Gaynor EC, Tanner ME (2011). "5'-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni." J Biol Chem 286(22);19392-8. PMID: 21489995
Tower91: Tower PA, Johnson LL, Ferro AJ, Fitchen JH, Riscoe MK (1991). "Synergistic activity of 5-trifluoromethylthioribose and inhibitors of methionine synthesis against Klebsiella pneumoniae." Antimicrob Agents Chemother 1991;35(8);1557-61. PMID: 1929327
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