Organic acidurias : proceedings of the ninth symposium of the Society for the Study of Inborn Errors of Metabolism / edited by J. Stern and C. Toothill.

  • Society for the Study of Inborn Errors of Metabolism.
Date:
1972
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Organic acidurias : proceedings of the ninth symposium of the Society for the Study of Inborn Errors of Metabolism / edited by J. Stern and C. Toothill. Source: Wellcome Collection.

    78/202 (page 62)
    p-HYDROXYPHENYLPYRUVIC ACID METABOLISM IN HEREDITARY TYROSINAEMIA Abstract of Paper by B. N. La Du Patients with hereditary tyrosinaemia show a consistent reduction in liver p-hydroxyphenylpyruvic acid (pHPPA) oxidase activity, liver cir¬ rhosis, and defective renal reabsorption of amino acids, glucose and phosphate. The hypertyrosinaemia and tyrosyluria associated with the liver and kidney abnormalities in these patients have led to the suggestion that a hereditary deficiency of pHPPA oxidase accounts for the bio¬ chemical and clinical features of the disorder. Enzymatic studies in our laboratory with liver obtained at autopsy and biopsy from over twenty- five patients with tyrosinaemia show a marked reduction, but not a complete loss, of pHPPA oxidase activity. Tyi osine transaminase and phenylalanine hydroxylase are also significantly reduced. Nevertheless, it is probable that altered tyrosine metabolism in this hereditary disease is secondary to another metabolic defect, as yet unknown, which results in inhibition of pHPPA oxidase. The accumulation of tyrosine metabolites, pHPPA and its metabolic derivatives, seems to contribute to the renal and Uver damage since dietary restriction of tyrosine intake ameliorates the metaboHc disease. Some of the alternative pathways of pHPPA metabolism include reduction to p-hydroxyphenyllactic acid by aromatic ketoacid reductase, and conversion of pHPPA to p-hydroxy phenylbenzaldehyde and p-hydroxybenzoic acid by oxidative cleavage of the side chain. Possible mechanisms by which the formation of these metabolites could contribute to the liver and kidney damage will be presented. Why tyrosyl metabolites can be toxic in hereditary tyrosin¬ aemia but not in other conditions of altered tyrosine metabolism (such as vitamin С deficiency and premature infants with tyrosyluria) will be discussed. 62