Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl-L-methionine.

摘要: S-Adenosyl-L-methionine (AdoMet) is one of Nature's most diverse metabolites, used not only in a large number biological reactions but amenable to several different modes reactivity. The types transformations which it involved include decarboxylation, electrophilic addition any the three carbons bonded central sulfur atom, proton removal at adjacent sulfonium, and reductive cleavage generate 5'-deoxyadenosyl 5'-radical intermediates. At physiological pH temperature, AdoMet subject spontaneous degradation pathways, first racemization chiral sulfonium group, takes place pH-independent manner. two remaining pathways are pH-dependent (1) intramolecular attack alpha-carboxylate group onto gamma-carbon, affording L-homoserine lactone (HSL) 5'-methylthioadenosine (MTA), (2) deprotonation C-5', initiating cascade that results formation adenine S-ribosylmethionine. Herein, we describe stability studies its selenium tellurium analogues, Se-adenosyl-L-selenomethionine Te-adenosyl-L-telluromethionine (SeAdoMet TeAdoMet, respectively), 37 degrees C constant ionic strength, use as probe their relative intrinsic reactivities. We find with nucleophilic afford HSL MTA exhibits pH-rate profile having titratable groups apparent pK(a) values 1.2 +/- 0.4 8.2 0.05 displaying first-order rate constants <0.7 x 10(-6) s(-1) less than 0.5, approximately 3 between 2 7, 15 greater 9. Degradation via C-5' follows an value 11.5. analogue decays significantly faster attack, also exhibiting 0.86 8.0 0.1 <7 0.9, 32 170 proceeds 14.1. Unexpectedly, TeAdoMet did decay observable either these pathways. Last, enzymatically synthesized was found racemize rates were consistent earlier (Hoffman, J. L. (1986) Biochemistry 25, 4444-4449); however, SeAdoMet detectable rates. In accompanying paper, information obtained model mechanism cyclopropane fatty acid synthase onium chalcogens methyl donors.