Stoner E, Starkman H, Wellner D, Wellner V P, Sassa S, Rifkind A B, Grenier A, Steinherz P G, Meister A, New M I
Pediatr Res. 1984 Dec;18(12):1332-6. doi: 10.1203/00006450-198412000-00023.
Metabolic and enzymatic studies in a patient with hereditary tyrosinemia demonstrated for the first time a deficiency of erythrocyte and hepatic glutathione. Markedly decreased hepatic fumarylacetoacetate hydrolase activity was demonstrated in this patient. The activities of hepatic enzymes not involved in tyrosine metabolism were also determined. Assay of mixed function oxidase activity demonstrated low levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase, suggesting decreased hepatic detoxification capacity. 5-Aminolevulinic acid dehydratase activity was undetectable. Succinylacetone (4,6-dioxoheptanoic acid), an abnormal metabolic product secondary to fumarylacetoacetate hydrolase deficiency was found in serum and urine. Succinylacetone was demonstrated to inhibit 5-aminolevulinic acid dehydratase in vitro, as did the urine, plasma, and red cell lysates of the patient.
对一名遗传性酪氨酸血症患者进行的代谢和酶学研究首次证实其红细胞和肝脏中谷胱甘肽缺乏。该患者肝脏中富马酰乙酰乙酸水解酶活性显著降低。还测定了肝脏中不参与酪氨酸代谢的酶的活性。混合功能氧化酶活性测定显示芳烃羟化酶和7-乙氧基香豆素脱乙基酶水平较低，提示肝脏解毒能力下降。未检测到5-氨基酮戊酸脱水酶活性。在血清和尿液中发现了富马酰乙酰乙酸水解酶缺乏继发的异常代谢产物琥珀酰丙酮（4,6-二氧代庚酸）。体外实验证明琥珀酰丙酮可抑制5-氨基酮戊酸脱水酶，该患者的尿液、血浆和红细胞裂解物也有此作用。
