Malic enzyme levels are increased by the activation of NADPH-consuming pathways: detoxification processes

The administration to rats of either t-butyl hydroperoxide or phenobarbital, compounds that are metabolized through detoxification processes, produces an increase in specific activity of the NADPH-consuming enzymes, glutathione reductase and NADPH-cytochrome c reductase. These compounds also produce a very significant increase in the specific activity of malic enzyme. Immunoprecipitation with a specific antibody for malic enzyme indicates that specific activity changes are the result of corresponding changes in the amounts of enzyme protein present. The administration of 1,3-bis(chloroethyl(-1-nitrosourea (a glutathione reductase inhibitor) together with t-butyl hydroperoxide abolishes any stimulation of malic enzyme activity. These results indicate that an increase in NADPH consumption induces the synthesis of malic enzyme. Alternatively, a protection of enzyme degradation cannot be rigorously excluded.