M. Kelner, J. Mclenithan, M. W. Anders
Jun 1, 1986
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0
Influential Citations
13
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Quality indicators
Journal
Biochemical pharmacology
Abstract
The enzymatic reduction of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) was studied with rat hepatic microsomal fractions. The reaction required NADPH and was inhibited by dioxygen and carbon monoxide, which shows that the reaction is catalyzed by cytochromes P-450. Moreover, when the reaction was studied in the presence of deuterium oxide, no deuterium was incorporated into the DDD, which suggests that a one-electron reduction of DDT to the 1,1-dichloro-2,2-bis(p-chlorophenyl)ethyl radical followed by hydrogen atom abstraction accounts for the formation of DDD. The microsomal reduction of DDT to DDD was stimulated markedly by several thiols, including glutathione. The stimulatory effect of thiols was concentration dependent and was not due to conservation of cytochrome P-450, because nonthiol antioxidants failed to stimulate the reaction. The mechanism of the stimulation is not understood, but thiols do not promote the formation of DDD by preventing the alkylation of microsomal lipids and, thereby, stimulating the formation of a reduced alkane. Finally, these results show that soluble, low-molecular weight compounds may enhance the activity of membrane-bound enzymes.