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The Metabolism of Gammekane and Related Compounds

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thesis
posted on 2021-11-05, 02:15 authored by Clark, Alan Geoffrey

1. A detailed kinetic study has been made of the glutathione S-aryl-transferases from the New Zealand grass grub (Costelytra zealandica) and from sheep liver. The insect enzyme behaves in accordance with a Michaelis-Menten model for two-substrate enzymes. It is inhibited by the sulphonphthaleins, phthaleins, fluoresceins and dicarboxylic acids competing with glutathione, while the sheep-liver enzyme is not susceptible to this type of inhibition. From this, and other data obtained from a study of the variation of kinetics with pH, it is proposed that two basic groups (possibly lysine residues) are involved in binding of glutathione to the insect enzyme, while only one such group appears in the sheep-liver enzyme. Binding of the aromatic substrate to the enzyme in both species may involve a histidine residue. 2. The accumulation of little significant radioactivity in diluant 2gamma-pentachlorocyclohexene (gamma-PCCH) during the in vitro metabolism of [14C]gamma-hexachlorohexane (gamma-HCH) suggests that the PCCH's are not formed as free intermediates during the metabolism of the HCH's. However, certain ambiguities introduced with the experimental techniques used preclude the complete exclusion of this possibility. 3. gamma-HCH, gamma-PCCH and delta-PCCH metabolized in vivo by M.domestica and C.zealandica and in vitro by preparations from both species, all produce as the principal metabolite a glutathione conjugate with chromatographic properties identical with those of authentic S-(2,4-dichlorophenyl)glutathione. There is, however some doubt as to the identity of the S-substituent moiety. 4. The in vitro metabolism of gamma-HCH and delta-PCCH is glutathione-dependent and is inhibited by various phthaleins and sulphonphthaleins. The in vivo metabolism of delta-PCCH in C.zealandica is profoundly affected by this type of compound, but its effects on the rate of metabolism in vivo of delata-HCH in M.domestica and C.zealandica are only marginal. 5. The enzyme concerned in the metabolism of delta-PCCH has been shown to differ from aryltransferase in M.domestica and C.zealandica by gel filtration techniques and by differences in activity in different enzyme preparations. The delta-PCCH-metabolising activity appears to be associated with a DDT dehydrochlorinase activity. In M.domestica, there appears to be, in addition, a second DDT dehydrochlorinase with only a low cross-specificity towards delta-PCCH.

History

Copyright Date

1967-01-01

Date of Award

1967-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Biochemistry

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Doctoral

Degree Name

Doctor of Philosophy

Victoria University of Wellington Item Type

Awarded Doctoral Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

Smith, J N