Sato P, Lindemann D
Biotechnol Appl Biochem. 1986 Apr-Jun;8(2-3):182-9.
Glutaraldehyde crosslinked, immunoprecipitated gulonolactone oxidase, injected intraperitoneally, has significant catalytic activity and is capable of providing long-term therapeutic benefit for the enzyme deficiency disease scurvy. The enzyme is tolerated even in repetitive doses. In the present study, however, we have found that when administered intra-arterially this modified enzyme is quite toxic even in single doses. Prior to administration the enzyme complex was filtered through a 5-microns filter. When administered intravascularly the enzyme is not nearly as active catalytically. In spite of this, activity can be detected in vivo as an elevation of plasma ascorbic acid and prolonged survival of guinea pigs fed without the vitamin. Following administration both activity and the enzyme complex are rapidly removed from the circulation. Liver and spleen are largely responsible for this uptake. Because of its toxicity intra-arterial injection of this form of the enzyme does not appear suitable for enzyme therapy.
经戊二醛交联、免疫沉淀的古洛糖酸内酯氧化酶,经腹腔注射后具有显著的催化活性,能够为酶缺乏疾病坏血病提供长期治疗益处。即使重复给药,该酶也能被耐受。然而,在本研究中,我们发现当经动脉给药时,这种修饰后的酶即使单次给药也具有相当大的毒性。给药前,酶复合物通过5微米滤器过滤。当经血管内给药时,该酶的催化活性远不如前。尽管如此,在体内仍可检测到活性,表现为血浆抗坏血酸水平升高以及喂食不含维生素食物的豚鼠存活时间延长。给药后,活性和酶复合物均迅速从循环中清除。肝脏和脾脏在很大程度上负责这种摄取。由于其毒性,这种形式的酶经动脉注射似乎不适合用于酶疗法。