Human biochemical genetics / by H. Harris.

  • Harris, Harry, 1919-1994.
Date:
1966
Catalogue details

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

Credit: Human biochemical genetics / by H. Harris. Source: Wellcome Collection.

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    PHENYLKETONURIA 45 The enzyme system The enzyme system concerned with the hydroxylation of phenyl¬ alanine to tyrosine was described by Udenfriend and Cooper (28), They found that it is present in water-soluble fractions from liver, but not from other tissues, and it appears to be specific for L-phenyl- alanine. The system is evidently complex and Mitoma(29) has shown that it consists of at least two protein fractions. One of these is very labile and is peculiar to the liver, and the other is more stable and occurs in other tissues as well. The reaction requires both reduced DPN and oxygen. Both protein fractions are necessary for the hydroxylation, and it has not been possible to separate the overall reaction into two steps. A direct attempt to discover whether any L-phenylalanine hydroxy¬ lase activity could be detected in the liver of Phenylketonurie patients was made by Jervis in 1953 (зо). He obtained fragments of Hver at autopsy from two Phenylketonurie patients and three controls. Crude liver extracts were tested in the system of Udenfriend and Cooper, and it was found that while activity could be demonstrated in the controls, no activity was detectable in the phenylketonurics. This result has since been confirmed by Wallace, Moldave and Meister (3i) using fresh biopsy specimens from a living Phenylketonurie patient and appropriate controls. These workers and also Mitoma, Auld and Udenfriend (32) have been able to show that the part of the enzyme system which is deficient in these patients is the labile fraction described by Mitoma. This fraction is only found in the liver. The stable fraction also present in other tissues appears to occur in Phenylketonurie patients in normal amounts. Some difficulties While there seems little doubt that most of the biochemical dis¬ turbances occurring in phenylketonuria can be directly referred to a deficiency in one component of the enzyme system normally con¬ cerned with the hydroxylation of phenylalanine to tyrosine, there still remain a number of puzzhng aspects of the biochemistry of this dis¬ order which require explanation. The mechanism by which increased quantities of o-hydroxyphenyl- acetic acid and possibly other hydroxyphenolic compounds are formed is still obscure. o-Hydroxyphenylacetic acid is certainly formed from phenylalanine, as has been demonstrated by ^^C-