Studies on the Induction and Repression of Enzymes in Rat Liver

Abstract

Abstract The enzyme, serine dehydratase (l-serine hydro-lyase, EC 4.2.1.13), has been purified by a previously unpublished method involving heat denaturation, ammonium sulfate treatment, Sephadex gel filtration, and hydroxylapatite chromatography. Antibodies to the pure enzyme have been prepared in rabbits and have been shown to be antigenically homogeneous. Utilizing the technique of pulse labeling of the enzyme in vivo with 14C-valine, it has been shown that administration of mixtures of amino acids dramatically increases the rate of synthesis of this enzyme in vivo without appreciably enhancing the synthesis of total soluble proteins. The amino acid, l-tryptophan, as well as the hormone, glucagon, also effects an increased rate of synthesis of the enzyme. Administration of glucose results in a complete cessation of enzyme synthesis whether administered from zero time or at a time interval thereafter at which the synthesis of the enzyme is completely resistant to the antibiotic, actinomycin D. Amino acid induction and glucose repression as well as hormonal induction by both glucagon and hydrocortisone occur in adrenalectomized animals. The effects of glucose administration on protein synthesis are not general since serum protein synthesis was not affected by this treatment. By prelabeling the enzyme and administering glucose with and without amino acids, it has been shown that glucose appears to effect primarily a cessation of enzyme synthesis and an increase of degradation of the enzyme. Studies of the composition of amino acid pools in the intact animal have shown that the different rates of synthesis seen in rats fed amino acids with respect to those fed glucose are not the result of differential labeling of the labeled precursor pool. The studies reported here show that the synthesis of rat liver serine dehydratase may be regulated by amino acids and glucose as well as by the hormones, hydrocortisone and glucagon, the latter being the most efficient inducer of the enzyme of those compounds studied. The repression of serine dehydratase synthesis in vivo by glucose appears in a number of ways to be analogous to catabolite repression seen in microorganisms.