ABSTRACT Mercapturic acid biosynthesis is an important biochemical process in detoxifying reactive electrophiles. Mercapturic acid biosynthesis has also been implicated in the expression of kidney selective toxicity of certain chemicals. The biosynthesis has been viewed as a result of interorgan processes of the liver and kidney with the formation of a glutathione conjugate in the liver as the initial step followed by cysteine conjugate formation in the kidney, and the end product mercapturic acid being excreted into urine. This interorgan model is largely based on the distribution of the involved enzymes in the liver and kidney of rats and mice. Although all enzyme systems required for mercapturic acid biosynthesis have been found in rat kidney, no report has been documented to demonstrate the independent capability of rat kidney for mercapturic acid biosynthesis. By using rat kidney homogenate and 1-chloro-2,4-dinitrobenzene (CDNB) as a model compound, this study showed that rat kidney was able to carry out the mercapturic acid biosynthesis independently without the involvement of liver. The formation of the glutathione conjugate of CDNB in the presence of rat kidney homogenate was an almost instantaneous reaction. The conversion of the glutathione conjugate to the corresponding cysteine conjugate and subsequently to the mercapturic acid was a time-dependent process.
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