The dehalogenation of iodouracil by cysteine. Intramolecular general-acid catalysis of cysteine addition to 5-iodouracil |
| |
Authors: | Frank A. Sedor Dan G. Jacobson Eugene G. Sander |
| |
Affiliation: | Department of Biochemistry, University of Florida, Gainesville, Florida 32610 USA |
| |
Abstract: | The rate-determining step of the cysteine-catalyzed deiodination of 5-iodouracil is the formation of 5-iodo-6-cysteinyl-5,6-dihydrouracil. The rate of the reaction depends upon the concentration of un-ionized 5-iodouracil and the following ionic species of cysteine; ?OOC(NH3+)CHCH2S?. Unlike the reaction of 2-mercapto-ethanol with 5-iodouracil, the cysteine reaction is not subject to catalysis by imidazolium ion and tris(hydroxymethyl)aminomethane hydrochloride. When the rates of cysteine reacting with 5-iodouracil are measured in both H2O and D2O, a large kinetic isotope effect is observed (), thus implicating the protonated α amino group of cysteine as an intramolecular general acid catalyst for the reaction. These results and possible mechanisms for the actual dehalogenation of the intermediate 5-iodo-6-cysteinyl-5,6-dihydrouracil are discussed in terms of a possible mechanism for enzymatic halopyrimidine dehalogenation. |
| |
Keywords: | To whom inquiries should be addressed. |
本文献已被 ScienceDirect 等数据库收录! |