Castillo M, Martinez-Cayuela M, Zafra M F, Garcia-Peregrin E
Department of Biochemistry and Molecular Biology, University of Granada, Spain.
Mol Cell Biochem. 1991 Jun 26;105(1):21-5. doi: 10.1007/BF00230371.
Phenylalanine, phenylpyruvate and phenylacetate produced a considerable inhibition of chick liver mevalonate 5-pyrophosphate decarboxylase while mevalonate kinase and mevalonate 5-phosphate kinase were not significantly affected. Phenolic derivatives of phenylalanine produced a similar inhibition of decarboxylase activity than that found in the presence of phenyl metabolites. The degree of inhibition was progressive with increasing concentrations of inhibitors (1.25-5.00 mM). Simultaneous supplementation of different metabolites in conditions similar to those in experimental phenylketonuria (0.25 mM each) produced a clear inhibition of liver decarboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase. To our knowledge, this is the first report on the in vitro inhibition of both liver regulatory enzymes of cholesterogenesis in phenylketonuria-like conditions. Our results show a lower inhibition of decarboxylase than that of reductase but suggest an important regulatory role of decarboxylase in cholesterol synthesis.
苯丙氨酸、苯丙酮酸和苯乙酸对鸡肝甲羟戊酸5-焦磷酸脱羧酶产生了显著抑制作用，而甲羟戊酸激酶和甲羟戊酸5-磷酸激酶未受到明显影响。苯丙氨酸的酚类衍生物对脱羧酶活性的抑制作用与在苯代谢产物存在时相似。随着抑制剂浓度增加（1.25 - 5.00 mM），抑制程度逐渐增强。在类似于实验性苯丙酮尿症的条件下（每种0.25 mM）同时补充不同代谢产物，对肝脏脱羧酶和3-羟基-3-甲基戊二酰辅酶A还原酶产生了明显抑制作用。据我们所知，这是关于在类似苯丙酮尿症条件下体外抑制胆固醇生成的两种肝脏调节酶的首次报道。我们的结果显示脱羧酶受到的抑制低于还原酶，但表明脱羧酶在胆固醇合成中具有重要的调节作用。
