Saheki T, Ueda A, Hosoya M, Kusumi K, Takada S, Tsuda M, Katsunuma T
Clin Chim Acta. 1981 Feb 5;109(3):325-35. doi: 10.1016/0009-8981(81)90318-1.
Enzymological and immunochemical analyses of the liver were preformed in seven Japanese patients with citrullinemia. Among the urea cycle enzymes in the liver, only the activity of argininosuccinate synthetase was specifically decreased to 2 to 50% of normal controls. Liver argininosuccinate synthetase of patients was indistinguishable from that of controls when tested immunochemically by Ouchterlony's double immunodiffusion technique with anti-rat argininosuccinate synthetase antiserum. Immunochemical analysis by means of the single radial immunodiffusion revealed that the decrease in the activity of liver argininosuccinate synthetase was explainable by a decrease in the amount of the enzyme protein in five patients, while the decrease in the activity in the other two patients was not accompanied by a decrease of enzyme protein. The Km values for the substrates of liver argininosuccinate synthetase of the former five were similar to those of the control, while the kinetic properties of the latter two were quite different in terms of higher Km values and negative cooperativity. From these results, we consider that citrullinemia may consist of more than one type including qualitative or quantitative abnormalities of argininosuccinate synthetase caused by some defects in certain genes or in the epigenetic processes in the liver.
对7例日本瓜氨酸血症患者进行了肝脏的酶学和免疫化学分析。在肝脏的尿素循环酶中，只有精氨琥珀酸合成酶的活性特异性降低至正常对照的2%至50%。当用抗大鼠精氨琥珀酸合成酶抗血清通过Ouchterlony双免疫扩散技术进行免疫化学检测时，患者肝脏中的精氨琥珀酸合成酶与对照的无法区分。通过单向放射免疫扩散进行的免疫化学分析显示，5例患者肝脏精氨琥珀酸合成酶活性的降低可归因于酶蛋白量的减少，而另外2例患者活性的降低并未伴随酶蛋白的减少。前5例患者肝脏精氨琥珀酸合成酶底物的Km值与对照相似，而后2例的动力学特性在较高的Km值和负协同性方面有很大不同。从这些结果来看，我们认为瓜氨酸血症可能由不止一种类型组成，包括由某些基因或肝脏表观遗传过程中的缺陷导致的精氨琥珀酸合成酶的定性或定量异常。
