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Isotope Effects on the Enzymatic and Non-Enzymatic Reactions of Chorismate
The important biosynthetic intermediate chorismate reacts thermally by two competitive pathways, one leading to 4-hydroxybenzoate via elimination of the enolpyruvyl side chain, and the other to prephenate by a facile Claisen rearrangement. Measurements with isotopically labeled chorismate derivative...
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| Main Authors: | , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
2005
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| Assuntos: | |
| Acesso em linha: | https://ncbi.nlm.nih.gov/pmc/articles/PMC2519010/ https://ncbi.nlm.nih.gov/pubmed/16159290 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1021/ja052929v |
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| Resumo: | The important biosynthetic intermediate chorismate reacts thermally by two competitive pathways, one leading to 4-hydroxybenzoate via elimination of the enolpyruvyl side chain, and the other to prephenate by a facile Claisen rearrangement. Measurements with isotopically labeled chorismate derivatives indicate that both are concerted sigmatropic processes, controlled by the orientation of the enolpyruvyl group. In the elimination reaction of [4-(2)H]chorismate, roughly 60% of the label was found in pyruvate after 3 h at 60 °C. Moreover, a 1.846±0.057 (2)H isotope effect for the transferred hydrogen atom and a 1.0374±0.0005 (18)O isotope effect for the ether oxygen show that the transition state for this process is highly asymmetric, with hydrogen atom transfer from C4 to C9 significantly less advanced than C—O bond cleavage. In the competing Claisen rearrangement, a very large (18)O isotope effect at the bond-breaking position (1.0482±0.0005) and a smaller (13)C isotope effect at the bond-making position (1.0118±0.0004) were determined. Isotope effects of similar magnitude characterized the transformations catalyzed by evolutionarily unrelated chorismate mutases from Escherichia coli and Bacillus subtilis. The enzymatic reactions, like their solution counterpart, are thus concerted [3,3]-sigmatropic processes in which C—C bond formation lags behind C—O bond cleavage. However, as substantially larger (18)O and smaller (13)C isotope effects were observed for a mutant enzyme in which chemistry is fully rate determining, the ionic active site may favor a somewhat more polarized transition state than that seen in solution. |
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