Abstract
Extensive metabolic and enzymatic studies in a patient with hereditary hepatorenal tyrosinemia demonstrated for the first time a deficiency of red cell and hepatic glutathione (GSH). Markedly decreased hepatic fumarylacetoacetate hydrolase activity was measured in this patient (1-16% of normal). The activity of enzymes not involved in tyrosine metabolism were also measured in liver tissue. Assay of mixed function oxidase activity demonstrated low levels of arylhydrocarbon hydroxylase and 7-ethoxycoumarindeethylase. This depression of mixed function oxidase activity may result in a decreased detoxification capacity of the liver. Delta-amino levulinic acid dehydratase (ALAD) activity was undetectable. Succinyl acetone (4,6 dioxoheptanoic acid), an abnormal metabolic product secondary to the fumarylacetoacetate hydrolase deficiency, was measurable in serum and urine. Succinyl acetone was demonstrated to inhibit ALAD in vitro, as did the urine, plasma and red cell lysates of the patient. The decreased GSH observed in this condition may play a role in the hepatic pathology and increased malignant potential in this disorder. Therefore, the decrease in GSH demonstrated in our patient suggests the possibility of a new mode of therapy.
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Stoner, E., Starkman, H., Wellner, D. et al. 1183 GLUTATHIONE IS DEFICIENT IN HEREDITARY TYROSINEMIA. Pediatr Res 15 (Suppl 4), 640 (1981). https://doi.org/10.1203/00006450-198104001-01209
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DOI: https://doi.org/10.1203/00006450-198104001-01209