A model for the regulation of delta-aminolaevulinate synthetase induction in rat liver.
A reciprocal relationship exists between the cytochrome P-450 content and delta-aminolaevulinate synthetase activity in adult rats. In young rats the basal delta-aminolaevulinate synthetase activity is higher and the cytochrome P-450 content is lower compared with the adult rat liver. Administration of allylisopropylacetamide neither induces the enzyme nor causes degradation of cytochrome P-450 in the young rat liver, unlike adult rat liver. Allylisopropylacetamide fails to induce delta-aminolaevulinate synthetase in adrenalectomized-ovariectomized animals or intact animals pretreated with successive doses of the drug, in the absence of cortisol. The cortisol-mediated induction of the enzyme is sensitive to actinomycin D. Allylisopropylacetamide administration degrades microsomal haem but not nuclear haem. Haem does not counteract the decrease in cytochrome P-450 content caused by allylisopropylacetamide administration, but there is evidence for the formation of drug-resistant protein-bound haem in liver microsomal material under these conditions. Phenobarbital induces delta-aminolaevulinate synthetase under conditions when there is no breakdown of cytochrome P-450. On the basis of these results and those already published, a model is proposed for the regulation of delta-aminolaevulinate synthetase induction in rat liver.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000315:Adrenalectomy; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D002369:Castration; D002951:Citrates / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D006418:Heme / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007504:Iron Radioisotopes; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008954:Models, Biological; D010634:Phenobarbital / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats
D002250:Carbon Radioisotopes; D002951:Citrates; D007504:Iron Radioisotopes; D003609:Dactinomycin; D000502:Allylisopropylacetamide; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase; D006854:Hydrocortisone; D010634:Phenobarbital