Hagmann W, Denzlinger C, Rapp S, Weckbecker G, Keppler D
Prostaglandins. 1986 Feb;31(2):239-51. doi: 10.1016/0090-6980(86)90050-x.
Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats in vivo after endotoxin treatment. The mercapturate N-acetyl-leukotriene E4 (N-acetyl-LTE4) represented a major metabolite eliminated into bile after injection of [3H]LTC4 as shown by cochromatography with synthetic N-acetyl-LTE4 in four different HPLC solvent systems. The identity of endogenous N-acetyl-LTE4 elicited by endotoxin in vivo was additionally verified by enzymatic deacetylation followed by chemical N-acetylation. The deacetylation was catalyzed by penicillin amidase. Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation. A N-acetyl-LTE4 concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection. Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE4. The mercapturic acid pathway, leading from the glutathione conjugate LTC4 to N-acetyl-LTE4, thus plays an important role in the deactivation and elimination of these potent endogenous mediators.
巯基尿酸的形成是外源性物质解毒的一条既定途径，在内毒素处理后的大鼠体内产生的半胱氨酰白三烯中得到了证实。如在四种不同的高效液相色谱（HPLC）溶剂系统中与合成的N - 乙酰 - 白三烯E4（N - 乙酰 - LTE4）共色谱分析所示，巯基尿酸N - 乙酰 - 白三烯E4（N - 乙酰 - LTE4）是注射[3H]白三烯C4（LTC4）后排入胆汁的主要代谢产物。通过酶促脱乙酰化然后化学N - 乙酰化，进一步证实了内毒素在体内引发的内源性N - 乙酰 - LTE4的身份。脱乙酰化由青霉素酰胺酶催化。高效液相色谱分离后，通过放射免疫测定法定量内源性半胱氨酰白三烯。在内毒素注射后30至60分钟收集的胆汁中，测定的N - 乙酰 - LTE4浓度为80 nmol/l。在此条件下，通过放射免疫测定法在胆汁中检测到的其他半胱氨酰白三烯含量不到N - 乙酰 - LTE4的5%。因此，从谷胱甘肽共轭物LTC4到N - 乙酰 - LTE4的巯基尿酸途径在这些强效内源性介质的失活和消除中起重要作用。
