Lertratanangkoon K, Denney D
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.
Biochem Pharmacol. 1993 Jun 22;45(12):2513-25. doi: 10.1016/0006-2952(93)90233-m.
When N-acetyl-S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cystein e (4-S-premercapturic acid) and N-acetyl-S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cystein e (3-S-premercapturic acid) were used as substrates in incubations with Hartley guinea pig kidney 9000 g supernatant preparations, the major products were the corresponding S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine and S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. At the end of the incubation period, the percentage recovery of these N-deacetylate cysteine conjugates accounted for 77 +/- 2% of the substrates, 3-S- and 4-S-premercapturic acids. Removal of the N-acetyl group from premercapturic acids to form the corresponding cysteine conjugates by kidney N-deacetylase(s) showed no preference with respect to the 3-S- and 4-S-positional isomeric conjugates. Other metabolites which included the known sulfur-containing acids, mercaptolactate and mercaptoacetate, were also detected. 3- and 4-Bromophenol and 3- and 4-bromothioanisole were also formed. The addition of pyridoxal-5'-phosphate to the kidney incubation mixture resulted in a 5-fold increase in the formation of phenols and thioanisoles, along with four different isomeric O- and S-methylated 3-S-and 4-S-bromothiocatechols and two S-methylated 3-S- and 4-S-bromodihydrobenzene thiolols. This result indicated that a pyridoxal phosphate-dependent C-S lyase(s) is involved in the formation of both phenol and thiophenolic metabolites from S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine and S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. Guinea pig liver 9000 g supernatant preparations did not N-deacetylate the 3-S- and 4-S-premercapturic acids to the same extent as kidney preparations, and this may account for decreased conversion of 3-S- and 4-S-premercapturic acids to 3- and 4-bromophenol and to thiophenolic products by liver preparations.
当N-乙酰基-S-(2-羟基-4-溴环己-3,5-二烯基)-L-半胱氨酸（4-S-前巯基尿酸）和N-乙酰基-S-(2-羟基-5-溴环己-3,5-二烯基)-L-半胱氨酸（3-S-前巯基尿酸）作为底物与哈特利豚鼠肾9000g上清液制剂一起孵育时，主要产物是相应的S-(2-羟基-4-溴环己-3,5-二烯基)-L-半胱氨酸和S-(2-羟基-5-溴环己-3,5-二烯基)-L-半胱氨酸。在孵育期结束时，这些N-脱乙酰半胱氨酸共轭物的回收率占底物3-S-和4-S-前巯基尿酸的77±2%。肾脏N-脱乙酰酶从前巯基尿酸中去除N-乙酰基以形成相应的半胱氨酸共轭物，对3-S-和4-S-位置异构共轭物没有偏好。还检测到了其他代谢物，包括已知的含磺酸、巯基乳酸和巯基乙酸。还形成了3-和4-溴苯酚以及3-和4-溴苯甲醚。向肾脏孵育混合物中添加磷酸吡哆醛导致酚类和苯甲醚的形成增加了5倍，同时还形成了四种不同的异构O-和S-甲基化的3-S-和4-S-溴硫代邻苯二酚以及两种S-甲基化的3-S-和4-S-溴二氢苯硫醇。这一结果表明，一种磷酸吡哆醛依赖性C-S裂解酶参与了从S-(2-羟基-4-溴环己-3,5-二烯基)-L-半胱氨酸和S-(2-羟基-5-溴环己-3,5-二烯基)-L-半胱氨酸形成酚类和硫酚类代谢物的过程。豚鼠肝脏9000g上清液制剂对3-S-和4-S-前巯基尿酸的N-脱乙酰程度不如肾脏制剂，这可能解释了肝脏制剂将3-S-和4-S-前巯基尿酸转化为3-和4-溴苯酚以及硫酚类产物的转化率降低的原因。
