The inhibition of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) dehydrochlorinase and gluthathione S-aryltransferase in grass-grub and housefly preparations

Abstract

The inhibition of DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] dehydrochlorinase and glutathione S-aryltransferase by diphenylmethane and triphenylmethane derivatives was examined. Bis-(3,5-dibromo-4-hydroxyphenyl)methane and similar compounds were excellent inhibitors of both enzymes, but only DDT dehydrochlorinase was inhibited by compounds similar to bis-(N-dimethylaminophenyl)methane. Colour salts of the basic triphenylmethyl dyes were excellent inhibitors of both enzymes. All the inhibitors examined appeared to act by competition with glutathione for its binding site on the two enzymes.

Cross-specificity in some vertebrate and insect glutathione-transferases with methyl parathion (dimethyl p-nitrophenyl phosphorothionate), 1-chloro-2,4-dinitrobenzene and S-crotonyl-N-acetylcysteamine as substrates

“…Other important xenobiotics detoxified by similar GSH-dependent enzymes are lindane (y-hexachlorocyclohexane) (Bradbury & Standen, 1959;Clark et al, 1969) and some organophosphates (Hutson et al, 1972). The insecticide DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] is also detoxified in resistant houseflies by a GSH-dependent enzyme that has some similarity to the various GSH transferases and which has been considered to be a possible member of this group (Balabaskaran & Smith, 1970).…”

Reversible inhibition in bimolecular rapid-equilibrium random-order enzyme systems. The effect of substrate–substrate and inhibitor–substrate interactions

“…DDT dehydrochlorinase is inhibited by a range of diphenylmethane derivatives that are GSH competitors in GSH transferases and are also structural analogues of DDT. The data quoted by Cohen et al (1964) and by Balabaskaran & Smith (1970) do not, however, show the parabolic form taken by * Abbreviation:…”

The separation of multiple forms of housefly 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)-ethane (DDT) dehydrochlorinase from glutathione S-aryltransferase by electrofocusing and electrophoresis

“…The detoxication of DDT* in houseflies is catalysed by the enzyme DDT dehydrochlorinase, which previous studies have shown to be inhibited by compounds that also inhibit GSH S-aryltransferase (Clark, Darby & Smith, 1967;Balabaskaran, Clark, Cundell & Smith, 1968;Balabaskaran & Smith, 1970). This is not unexpected, since both enzymes have a requirement for GSH, in the one case as a substrate and as a cofactor or activator in the other.…”