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- W8614354 abstract "Review of the literature of the past 40 years on tyrosine and its toxicity shows that no direct link between this aromatic amino acid and carcinogenesis has been well established. Ten years ago, studies of tyrosine toxicity in mice suggested the formation of an epoxide adduction product presumably derived from tyrosine by way of the liver microsomal detoxification system. Another study showed an increased frequency of hepatomas following long-term treatment with para-hydroxyphenyllactic acid, a tyrosine derivative occurring in the absence of p-hydroxyphenylpyruvate oxydase activity. Recently, studies on hereditary tyrosinemias (Type I) have indicated that the primary enzyme defect in these diseases is a deficiency of liver and renal fumarylacetoacetase. This results in an accumulation of natural alkylating derivatives of homogentisic acid such as maleyl- and fumarylacetoacetate in liver. Adduction of these compounds by glutathione is demonstrated by the presence of the mercapturic acid S-2-fumaryl-acetone-N-acetylcysteine in urine of patients. This adduct is also present in the urine of a number of heterozygote carriers after oral loads consisting of small quantities of homogentisic acid. In this report, we present the results of preliminary animal studies on the biochemical nature of the toxic effects of these tyrosine derivatives in these diseases along with preliminary data on the influence of fumarylacetone on protein synthesis in cultured eucaryotic cells. Fumarylacetone reacts as a natural alkylating agent and may, along with maleylacetoacetate, be responsible for the high incidence of late-onset hepatoma in the clinical chronic forms of hereditary tyrosinemias.KeywordsAromatic Amino AcidMercapturic AcidTyrosine AminotransferaseHomogentisic AcidButhionine SulfoximineThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves." @default.
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- W8614354 date "1986-01-01" @default.
- W8614354 modified "2023-09-23" @default.
- W8614354 title "Hereditary Tyrosinemias (Type I): A New Vista on Tyrosine Toxicity and Cancer" @default.
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- W8614354 doi "https://doi.org/10.1007/978-1-4613-1835-4_17" @default.
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