Induction of δ-Aminolevulinic Acid Synthetase in Isolated Rat Liver Cell Suspensions

Autor: Anthony M. Edwards, W. H. Elliott
Rok vydání: 1974
Předmět:
Zdroj: Journal of Biological Chemistry. 249:851-855
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(19)43006-8
Popis: The control of total δ-aminolevulinic acid (ALA) synthetase activity in mammalian liver has been studied in isolated rat liver cell suspensions. Induction of ALA synthetase by the drug, allylisopropyl-acetamide (AIA) at a rate comparable to that of drug-stimulated induction in fasted rats could be achieved in the isolated cells; induction was largely dependent on the presence of adenosine 3' : 5'-monophosphate (cyclic AMP) or its dibutyryl derivative. At optimal concentrations either AIA (1.2 mm) or dibutyryl cyclic AMP (50 µm) alone caused little induction, but in combination caused a 4- to 5-fold increase of ALA synthetase activity in isolated cells over a 6-hour period. It is suggested that the cyclic AMP dependence of induction by drugs, also demonstrated for the drug 3,5-dicarbethoxydihydrocollidine, explains glucose repression of ALA synthetase observed in vivo. Glucose had no effect on induction by AIA ± dibutyryl cyclic AMP in isolated cells. Despite reports that glucocorticoids are required for induction in vivo, addition of hydrocortisone succinate to concentrations maximally effective in inducing hepatic tyrosine aminotransferase had little effect on the increase in total ALA synthetase activity stimulated by AIA ± dibutyryl cyclic AMP in isolated cells. Induction was prevented by addition of cycloheximide or actinomycin D to cell suspensions.
Databáze: OpenAIRE