Relationship between the soluble glutathione-dependent delta 5-3-ketosteroid isomerase and the glutathione S-transferases of the liver.
Soluble, glutathione-stimulated delta 5-3-ketosteroid isomerase (EC 5.3.3.A) activity of human and rat liver resides in very basic proteins with molecular weights of about 45,000 which are present in high concentrations in these tissues. Physiochemical and immunological evidence is presented for the identity of the proteins responsible for this enzymatic activity with the glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18) that conjugate glutathione with a variety of electrophilic compounds. In the rat, the steroid isomerase is associated principally with the major transferase (B), which is also known as ligandin, and has the versatility to bind various hydrophobic compounds such as bilirubin, corticosteroids, and metabolites of a number of carcinogens. Other rat liver-glutathione S-transferase species are far less active in the steroid isomerization reaction. The delta 5-3-ketosteroid isomerase activity of human liver is more uniformly distributed among the five glutathione S-transferases that have been described. Steroid isomerization differs fundamentally from other reactions promoted by glutathione S-transferases in that glutathione is not consumed in the reaction. However, because the transferase enzymes promote nucleophilic attack by glutathione on a variety of largely foreign organic substrates, a similar mechanism may be involved in the isomerase reaction. Delta 5-3-ketosteroids are among the few known naturally occurring substrates for these enzymes.
D000818:Animals; D001665:Binding Sites; D004789:Enzyme Activation; D005978:Glutathione / Q000494:pharmacology; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007525:Isoelectric Focusing; D007535:Isomerases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D051381:Rats; D013251:Steroid Isomerases / Q000302:isolation & purification / Q000378:metabolism*
D005982:Glutathione Transferase; D007535:Isomerases; D013251:Steroid Isomerases; D005978:Glutathione
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