Sanghvi A, Parikh B
Biochim Biophys Acta. 1978 Oct 25;531(1):79-85. doi: 10.1016/0005-2760(78)90184-4.
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.
在给卟啉原性化学物质烯丙基异丙基乙酰胺单次给药（400毫克/千克）后12小时，禁食大鼠的羟甲基戊二酰辅酶A还原酶活性几乎增加了一倍。在基础期以及午夜（昼夜节律中该酶活性最高时）均观察到该药物对酶活性的这种加倍作用。放线菌酮，无论是单独给药还是与该药物同时给药，都将酶活性降低到非常低的水平。单独给予放线菌素D可阻止夜间还原酶活性的正常升高；然而，当与该药物一起给药时，它会抑制但不会完全抑制烯丙基异丙基乙酰胺的诱导作用。这些数据表明，要观察烯丙基异丙基乙酰胺对羟甲基戊二酰辅酶A还原酶活性的刺激作用需要蛋白质合成。还描述了还原酶测定方法的一种改进，其中用3M盐酸使测定的终产物甲羟戊酸内酯从甲羟戊酸中形成最大化。使用该方法，观察到甲羟戊酸内酯的产率在90%范围内保持一致，因为使用3M盐酸可防止甲羟戊酸脱水生成δ3,4-甲基-δ-戊内酯。
