Kim B D, Keenen S, Bodnar J K, Sander E G
J Biol Chem. 1976 Nov 25;251(22):6909-14.
Incubation of 5-iodo-5,6-dihydrouracil (IH2Ura) with soluble rat liver enzymes at 37 degrees, pH 8.2, results in the rapid release of iodide ion. The second product resulting from the carbon skeleton of the dihydropyrimidine ring system is 2-amino-2-oxazoline-5-carboxylic acid (I). Ultraviolet absorbance measurements at 225 nm, where both IH2Ura and iodide ion absorb, indicate that IH2Ura dehalogenation is a two-step process. The first step, which is enzyme-dependent, involves dihydropyrimidine amidohydrolase (EC 3.5.2.2.)-catalyzed hydrolysis of the IH2Ura ring system presumably to yield 2-iodo-3-ureidopropionate. The enzyme preparations also catalyze the hydrolysis of 5-bromo-5,6-dihydrouracil, 5,6-dihydrouracil, and 5,6-dihydrothymine, the latter two of which are the natural substrates for dihydropyrimidine amidohydrolase. The second step in IH2Ura dehalogenation involves the nonenzymatically catalyzed, pH-independent intramolecular cyclization of 2-iodo-3-ureidopropionate via nucleophilic attack of the ureido oxygen atom on carbon-2 resulting in iodide ion and the oxazoline (I) as final products. The results are discussed relative to the role of pyrimidine catabolizing enzymes in 5-halopyrimidine dehalogenation.
在37摄氏度、pH值为8.2的条件下，将5-碘-5,6-二氢尿嘧啶（IH2Ura）与可溶性大鼠肝脏酶一起孵育，会导致碘离子迅速释放。二氢嘧啶环系统碳骨架产生的第二种产物是2-氨基-2-恶唑啉-5-羧酸（I）。在225nm处进行的紫外吸收测量表明，IH2Ura脱卤是一个两步过程，在该波长下IH2Ura和碘离子都会吸收。第一步是酶依赖性的，涉及二氢嘧啶酰胺水解酶（EC 3.5.2.2.）催化的IH2Ura环系统水解，大概产生2-碘-3-脲基丙酸酯。这些酶制剂还催化5-溴-5,6-二氢尿嘧啶、5,6-二氢尿嘧啶和5,6-二氢胸腺嘧啶的水解，后两者是二氢嘧啶酰胺水解酶的天然底物。IH2Ura脱卤的第二步涉及2-碘-3-脲基丙酸酯通过脲基氧原子对碳-2的亲核攻击进行的非酶催化、与pH无关的分子内环化，最终产生碘离子和恶唑啉（I）。讨论了这些结果与嘧啶分解代谢酶在5-卤代嘧啶脱卤中的作用的关系。
