Giger U, Meyer U A
FEBS Lett. 1983 Mar 21;153(2):335-8. doi: 10.1016/0014-5793(83)80637-1.
The effects of succinylacetone, a tyrosine metabolite, on the hepatic biosynthesis of heme and cytochrome P450 were studied in primary culture of chick embryo hepatocytes. Succinylacetone potentiated the phenobarbital-mediated induction of delta-aminolevulinate synthase, strongly inhibited porphobilinogen synthase activity, reduced cellular heme concentration and impaired induction of cytochrome P450. Enhanced induction of delta-aminolevulinate synthase and decreased cytochrome P450 induction may be explained by the succinylacetone-mediated inhibition of porphobilinogen synthase and the subsequent depletion of intracellular heme, since these effects of succinylacetone were reversed by addition of heme. These results suggest clinical implications for patients with tyrosinemia, who accumulate succinylacetone.
在鸡胚肝细胞原代培养中，研究了酪氨酸代谢产物琥珀酰丙酮对肝脏血红素生物合成及细胞色素P450的影响。琥珀酰丙酮增强了苯巴比妥介导的δ-氨基乙酰丙酸合酶的诱导作用，强烈抑制胆色素原合酶活性，降低细胞血红素浓度并损害细胞色素P450的诱导。δ-氨基乙酰丙酸合酶诱导增强及细胞色素P450诱导减少可能是由于琥珀酰丙酮介导的胆色素原合酶抑制及随后细胞内血红素的消耗所致，因为添加血红素可逆转琥珀酰丙酮的这些作用。这些结果提示了对于蓄积琥珀酰丙酮的酪氨酸血症患者的临床意义。
