Tanguay R M, Jorquera R, Poudrier J, St-Louis M
LGCM, Centre de recherche du CHUL, Ste-Foy, Québec, Canada.
Acta Biochim Pol. 1996;43(1):209-16.
Hereditary tyrosinemia type I (HT I, McKusick 276,700) is a metabolic disease with a pattern of autosomal recessive inheritance. The disease is caused by a deficiency of the enzyme involved in the last step in the degradation of the amino acid tyrosine, fumarylacetoacetate hydrolase (FAH). The result of this block is the accumulation of catabolites some of which have been proposed to be highly toxic due to their alkylating potential. In humans, hereditary tyrosinemia is often associated with the development of hepatocellular carcinoma in young patients. The reasons for the high incidence of hepatocellular carcinoma are unknown but it has been suggested that it may be caused by accumulated metabolites such as fumarylacetoacetate (FAA) and maleylacetoacetate (MAA). The various mutational defects in the FAH gene are reviewed. The use of two mouse models of this disease to study the molecular basis of the pathologies associated with HT I are discussed. Finally, some preliminary data on the mutagenic potential of FAA and MAA in a gene reversal assay are presented.
遗传性I型酪氨酸血症（HT I，麦库西克编号276,700）是一种常染色体隐性遗传模式的代谢疾病。该疾病由参与氨基酸酪氨酸降解最后一步的酶——延胡索酰乙酰乙酸水解酶（FAH）缺乏所致。这种阻断的结果是分解代谢物的积累，其中一些因具有烷基化潜力而被认为具有高毒性。在人类中，遗传性酪氨酸血症常与年轻患者肝细胞癌的发生有关。肝细胞癌高发的原因尚不清楚，但有人认为可能是由诸如延胡索酰乙酰乙酸（FAA）和马来酰乙酰乙酸（MAA）等积累的代谢物引起的。本文综述了FAH基因的各种突变缺陷。讨论了利用该疾病的两种小鼠模型来研究与HT I相关病理的分子基础。最后，给出了在基因逆转试验中FAA和MAA诱变潜力的一些初步数据。
