Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I)

Hereditary tyrosinemia is characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. FAH was purified from rat and human liver and was used to immunize rabbits. Specific antibodies were used to probe protein ext...

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Bibliographic Details
Published in:American journal of human genetics 1990-08, Vol.47 (2), p.308-316
Main Authors: TANGUAY, R. M, VALET, J. P, LESCAULT, A, DUBAND, J. L, LABERGE, C, LETTRE, F, PLANTE, M
Format: Article
Language:English
Subjects:
Amino Acid Metabolism, Inborn Errors - enzymology
Amino Acid Metabolism, Inborn Errors - genetics
Aminoacid disorders
Animals
Biological and medical sciences
Errors of metabolism
Humans
Hydrolases - deficiency
Hydrolases - genetics
Hydrolases - isolation & purification
Immunoblotting
Liver - enzymology
Medical sciences
Metabolic diseases
Organ Specificity
Rats
Tyrosine - blood
tyrosinemia
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Summary:Hereditary tyrosinemia is characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. FAH was purified from rat and human liver and was used to immunize rabbits. Specific antibodies were used to probe protein extracts of livers and other tissues of normal and tyrosinemic patients. No immunoreactive FAH band was observed on immunoblots of liver, kidneys, and lymphocytes from patients presenting with the acute form of hereditary tyrosinemia. Patients with the chronic form had immunoreactive FAH at a level approximately 20% of normal liver values, which was correlated with the measured enzymatic activity. Immunoblot analysis of aborted fetal tissues revealed normal FAH immunoreactivity in normal liver and kidneys. No FAH immunoreactivity was found in liver and kidneys of tyrosinemic fetuses. The presence of FAH immunoreactivity in normal fetal tissues suggests that deficient FAH activity in tyrosinemia is not simply related to a developmentally regulated expression of the enzyme. By this immunoblot assay, FAH was detected in most human tissues, with maximal immunoreactivity in liver and kidneys and with only trace amounts in chorionic villi and cultured amniocytes. These data confirm that the primary defect in the acute form of hereditary tyrosinemia is an absence of FAH. Moreover, these data suggest that both clinical forms of the disease have a different molecular basis.
ISSN:0002-9297
1537-6605