Induction of Hepatic Enzymes by Adenosine 3′,5′-Monophosphate in Organ Culture

作者：Wesley D. Wicks · 发表于：Journal of Biological Chemistry · 年份：1969 · DOI：10.1016/s0021-9258(17)36440-2 · 被引用次数：191 · 研究领域：Metabolism and Genetic Disorders、Cancer, Hypoxia, and Metabolism、Biochemical and Molecular Research

Abstract In fetal rat liver maintained in organ culture, the activity of tyrosine-α-ketoglutarate transaminase (L-tyrosine:2-oxo-glutarate aminotransferase, EC 2.6.1.5) is elevated by adenosine 3',5'-monophosphate (cyclic AMP) and those hormones (glucagon, catecholamines) that stimulate formation of this nucleotide, as well as by hydrocortisone and insulin. Hydrocortisone is the most effective inducer, but the lag period for response to glucagon, isoproterenol, and cyclic AMP is somewhat shorter than with the steroid. The results obtained with combinations of the different inducers suggest that there may be three basic mechanisms for regulation of the transaminase: one stimulated by hydrocortisone, one by insulin, and one by cyclic AMP. The effect of cyclic AMP on the transaminase was found to be due to an increased rate of enzyme synthesis as determined by immunochemical isotopic analysis. Very low concentrations of either hydrocortisone or cyclic AMP markedly potentiated the effects of optimal concentrations of the other. Glucagon, isoproterenol, and cyclic AMP were found to stimulate the activity of another hepatic enzyme, soluble phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase transphosphorylating, EC 4.1.1.32), but not glucose 6-phosphatase (D-glucose 6-phosphate phosphohydrolase, EC 3.1.3.9) within a 4-hour period. Hydrocortisone and insulin did not affect either of these enzymes; rather, insulin inhibited induction of the carboxykinase by glucagon, is...