Incefy G S, Kappas A
Proc Natl Acad Sci U S A. 1974 Jun;71(6):2290-4. doi: 10.1073/pnas.71.6.2290.
The porphyrin-heme pathway is controlled in the liver at the level of the mitochondrial enzyme delta-aminolevulinate synthase (EC 2.3.1.37), a protein inducible in cultured avian hepatocytes by a variety of chemicals including certain 5beta-metabolites of steroid hormones. The great sensitivity of the induction process to inhibition by agents known to block transcriptional activity of genetic material suggests that some control mechanism may be operating at this level to regulate the formation of the enzyme. We report here enhancement of nuclear RNA synthesis and of Mn(2+)-(NH(4))(2)SO(4)-stimulated DNA-dependent RNA polymerase (EC 2.7.7.6) activities by the 5beta-steroid metabolite, 3alpha-hydroxy-5beta-androstan-17-one (etiocholanolone), in cultured avian hepatocytes during induction of the enzyme. These changes were demonstrated in the G(1) phase of the hepatocyte cell cycle at a time when DNA synthesis is constant. Our findings support the view that one of the early steps in the process of induction of delta-aminolevulinate synthase by steroid metabolites requires new RNA synthesis, very probably messenger RNA, suggesting a 5beta-steroid transcriptional control mechanism for induction of this protein.
卟啉 - 血红素途径在肝脏中由线粒体酶δ-氨基乙酰丙酸合酶（EC 2.3.1.37）调控，该蛋白在培养的禽肝细胞中可被多种化学物质诱导，包括某些甾体激素的5β-代谢产物。诱导过程对已知能阻断遗传物质转录活性的试剂抑制作用极为敏感，这表明可能在此水平存在某种控制机制来调节该酶的形成。我们在此报告，在培养的禽肝细胞中，于该酶诱导期间，5β-甾体代谢产物3α-羟基 - 5β-雄甾烷 - 17 - 酮（本胆烷醇酮）可增强核RNA合成以及Mn(2 +)-(NH(4))(2)SO(4)刺激的依赖DNA的RNA聚合酶（EC 2.7.7.6）活性。这些变化在肝细胞周期的G(1)期得到证实，此时DNA合成保持恒定。我们的研究结果支持这样一种观点，即甾体代谢产物诱导δ-氨基乙酰丙酸合酶过程中的早期步骤之一需要新的RNA合成，很可能是信使RNA，这表明存在一种5β-甾体转录控制机制来诱导该蛋白。
