INDUCTION OF A PROTEIN INHIBITOR TO ORNITHINE DECARBOXYLASE BY END PRODUCTS OF ITS REACTION

Putrescine, the end product of ornithine decarboxylase (ODC; L-ornithine carboxylase, EC 4.1.1.17) action, induces the synthesis of a protein(s), in L1210, neuroblastoma and H-35 cells as well as in rat liver, which inhibits ODC activity. Spermidine and spermine, distal products of ODC activity, also induce the synthesis of a similar protein in H-35 cells. These ODC-inhibitors are heat-labile, trypsin-sensitive; their induction is dependent upon protein synthesis. They have short half-lives which range from 18 to 66 min; these half-lives are similar to those of the ODC derived from the same source. They are noncompetitive inhibitors of ODC activity with an apparent MW of 26,500. Each inhibitor crossreacts with the ODC''s of the other cells and forms an enzyme-inhibitor complex which is stable during Sephadex chromatography; after treatment with ammonium sulfate, enzyme and inhibitor activities can be dissociated and recovered intact from the same column. The name antizyme is proposed for proteins whose synthesis is induced by the proximal or distal products of the enzyme they inhibit.