Ambrus C M, Sharma S D, Horváth C, Kalghatgi K, Anthone S, Ambrus J L, Cooley C, Mirand E A
J Pharmacol Exp Ther. 1983 Mar;224(3):598-602.
Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.
开发了固定化苯丙氨酸解氨酶（PAL）的中空纤维酶反应器，用于体内消耗循环血液中的苯丙氨酸（Phe）。为了探索其临床应用的安全性，在大型动物模型上进行了一系列实验。在患有实验性高苯丙氨酸血症的麻醉、肝素化犬和猴中应用反应器2小时期间，红细胞、白细胞和血小板水平没有变化。由于PAL催化Phe分解产生氨，未观察到血尿素氮增加。据报道，另一种代谢产物反式肉桂酸无毒。将PAL反应器重复应用于同一动物未产生不良生理或免疫反应。这些数据表明，PAL反应器在体内用于控制苯丙酮尿症患者因发热、感染或妊娠导致的过量Phe可能是安全的，否则这些患者通过低苯丙氨酸饮食保持平衡。PAL反应器的应用可为酶缺乏疾病的体外酶替代提供一个模型。
