Effect of protease inhibitors on protein degradation in rat hepatoma cells II. Effects on ornithine decarboxylase and tyrosine aminotransferase

Tyrosine aminotransferase (EC 2.6.1.5) and ornithine decarboxylase (EC 4.1.1.17) are both inducible, pyridoxal phosphate-requiring enzymes, which undergo rapid turnover in cultured rat hepatoma (HTC) cells, as measured by loss of enzyme activity following inhibition of protein synthesis. Under these conditions tosylphenylalanine chloromethyl ketone (Tos-PheCh2Cl) and tosyllysine chloromethyl ketone (Tos-LysCh2Cl) both almost completely inhibit the loss of tyrosine aminotransferase activity, implying the involvement of serine proteases in this process. Depletion of intracellular ATP levels to virtually zero also completely inhibits the apparent degradation of tyrosine aminotransferase. In contrast, the decline in ornithine decarboxylase activity following inhibition of protein synthesis is stimulated by both Tos-PheCH2Cl and Tos-LysCH2Cl, although with Tos-PheCH2Cl this stimulation is followed after 45 min by a complete inhibition of apparent degradation. ATP starvation inhibits the loss of ornithine decarboxylase activity by only 50%. © 1974.

Duke Scholars

Author Brigid L. M. Hogan Cell Biology