Stimulation of hydroxymethylglutaryl-CoA reductase activity after a single dose of the porphyrogenic chemical, allylisopropylacetamide.
Hydroxymethylglutaryl-CoA reductase activity in fasting rats was almost doubled 12 h following a single dose (400 mg/kg) of the porphyrogenic chemical allylisopropylacetamide. This doubling effect of the drug on enzyme activity was observed during the basal period, as well as at midnight, when it is maximal in the diurnal rhythm. Cycloheximide, whether given alone or simultaneously with the drug, reduced the enzyme activity to very low levels. Actinomycin D administered alone prevented the normal rise in reductase activity which occurs at night; however, when administered with the drug, it inhibited but did not completely suppress the inducing effect of allylisopropylacetamide. These data suggest a requirement for protein synthesis to observe the stimulating effect of allylisopropylacetamide on hydroxymethylglutaryl-CoA reductase activity. A modification in the reductase assay is also described wherein the formation of mevalonolactone from mevalonic acid, the end-product of the assay, is maximized with 3 M HCl. Using this procedure, consistent yields of mevalonolactone in the 90% range are observed since the use of 3M HCl prevents dehydration of mevalonic acid to delta3, 4-methyl-delta-valerolactone.
D000081:Acetamides / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005215:Fasting; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats
D000081:Acetamides; D000502:Allylisopropylacetamide; D006903:Hydroxymethylglutaryl CoA Reductases