Human biochemical genetics / by H. Harris.

  • Harris, Harry, 1919-1994.
Date:
1959
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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    42 aminoacid metabolism: i phenylalanine and also of all the other substances usually found, including the indoles, is abolished (Fig. 7). This correction of the various biochemical abnormalities characteristic of the disease has been maintained for many months and during this period the rate of growth has been satisfactory and the children did not go into negative nitrogen balance. The metabolic lesion Rose and his collegues (24) showed that, in man, phenylalanine is an indispensable dietary constituent and that its omission from the diet is followed by pronounced negative nitrogen balance. Thus phenyl¬ alanine is an 'essential' aminoacid. Tyrosine, however, is not 'essential', though it may become a limiting factor for growth and nutrition if the diet does not contain enough phenylalanine. It appears that while tyrosine can be formed from phenylalanine, the formation of phenylalanine from tyrosine is not possible. This irreversible conversion of phenylalanine to tyrosine is now generally believed to be the first step in the oxidation of phenyl¬ alanine, derived either from the protein in the diet or from the break¬ down of tissue protein. It has a central place in the intermediary metabolism of phenylalanine in the normal subject. A subsidiary series of reactions in which phenylalanine may be normally concerned involve changes in the side-chain. They are illustrated in Fig. 8. It may be reversibly converted to phenylpyruvic acid and phenyllactic acids, and the phenylpyruvic acid can be irreversibly changed to phenylacetic acid. Phenylacetic acid in man is mainly conjugated with glutamine to give phenylacetylglutamine which is excreted in the urine. Appreciable quantities of phenyl¬ acetylglutamine occur in normal urine (25) and this is presumably derived from phenylalanine via phenylpyruvic acid. The characteristic biochemical findings in the blood, cerebrospinal fluid, and the urine of Phenylketonurie patients can for the most part be readily understood on the hypothesis that the enzyme system normally concerned in the conversion of phenylalanine to tyrosine is in some way defective. Under these circumstances one would expect the composition of the body fluids to reflect a block in intermediary metabolism at this point. Phenylalanine derived from protein in the food, or from the breakdown of tissue proteins would tend to accumu¬ late in the blood and cerebrospinal fluid and be excreted in abnormal amounts in the urine. Phenylpyruvic acid, phenyllactic acid, and