A cytosolic high M cysteine-S-conjugate -lyase (apparent M of 330,000) has been partially purified from rat kidneys. The high M lyase is also present in the mitochondria. The purified enzyme contains at least two proteins with apparent M values of 50,000 and 70,000. Activity is stimulated by dithiothreitol, -keto acids, and pyridoxal 5`-phosphate; aminooxyacetate is an inhibitor. The enzyme catalyzes a competing (half) transamination reaction between pyridoxal 5`-phosphate cofactor and cysteine-S-conjugate substrate; added -keto acids promote conversion of active site pyridoxamine 5`-phosphate to pyridoxal 5`-phosphate. The enzyme also catalyzes a full (but weak) transamination between L-phenylalanine and -keto--methiolbutyrate. The purified enzyme is not recognized by polyclonal rabbit antibodies to cytosolic rat kidney glutamine transaminase K (another cysteine-S-conjugate -lyase of rat kidney) and has no obvious similarities to other pyridoxal 5`-phosphate-containing enzymes. In addition to catalyzing elimination reactions with S-(1,2-dichlorovinyl)-L-cysteine and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, the enzyme reacts with leukotriene E and 5`-S-cysteinyldopamine. Finally, the cytosolic and mitochondrial enzymes are activated by -ketoglutarate. Thus, the possibility must be considered that, in kidneys of animals exposed to various cysteine conjugates, the high M lyase contributes to the generation of pyruvate, ammonia, and reactive fragments in vivo. Many cysteine conjugates are nephrotoxic, and the high M lyase(s) may be involved.

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