Phenylpyruvic oligophrenia

D2. Dancis, J., and Balis, M. E., A possible mechanism for the disturbance in tyrosine metabolism in phenylpyruvic oligophrenia. Pediatrics 16, 63-67 (1955). 

J3. Jervis, G. A., Studies on phenylpyruvic oligophrenia. The position of the metabolic error. J. Biol. Chem. 169, 651-656 (1947). 

J4. Jervis, G. A., Phenylpyruvic oligophrenia (phenylketonuria). Research Pubis. Assoc. Research Nervous Mental Disease 33, 259-282 (1954). 

M10. Meister, A., Udenfriend, S., and Bessman, S. P., Diminished phenylketonuria in phenylpyruvic oligophrenia after administration of L-glutamine, L-glutamate, or L-asparagine. J. Clin. Invest. 36, 619-626 (1956). 

Chemical and metabolic studies on phenylalanine. II. Phenylalanine content of the blood and spinal fluid in phenylpyruvic oligophrenia. Ibid., 134, 105 (1940). With G. A. Jervis, D. Bolling, and E. Kanze. 

Classical phenylketonuria is an hereditary defect in the synthesis of Phe hydroxylase (the enzyme may be absent or inactive), which affects about 1 infant in 10,000. These individuals are unable to convert Phe into tyrosine, and the major route of Phe metabolism is thus blocked. Phenylpyruvate and phenylacetic acid are excreted in the urine. The condition is accompanied by defective pigmentation and, if untreated, by severe mental retardation (hence the other name, phenylpyruvic oligophrenia, also known as Polling s syndrome). Tlie urine of newborn infants is now routinely tested (Guthrie test) for the presence of phenylketones the condition can be compensated by a diet low in phenylalanine, and the typic mental retardation is thereby avoided. Other types of phenylketonuria are due to defective reduction or synthesis of dihydrobiopterin (see Inborn errors of metabolism). 

Phenylketonuria or phenylpyruvic oligophrenia is a disease transmitted as a typical mendelian recessive character and manifested by a specific biochemical and neurological syndrome. Biochemically, phenylketonuria is characterized by increased levels of phenylalanine in the blood, cerebrospinal fluid, and urine. In addition to phenylalanine derivatives, a few indole derivatives are found in the urine of phenylketonuric patients. 

Udenfriend, S., Bessman, S.P. The hydroxylation of phenylalanine and antipyrine in phenylpyruvic oligophrenia. J. biol. Chem. 203, 961-966 (1953)... 

The series of reactions outlined accounts for most of the oxidation of phenylalanine and tyrosine in animals. Conversion of phenylalanine to phenylpyruvic acid also occurs, and the keto acid is a major excretion product in the disease phenylpyruvic oligophrenia. Armstrong and collaborators have shown that a very large number of phenolic compounds, presumably derived from aromatic amino acids, also occur in human urine. The reactions that are responsible have not been defined. 

Phenylpyruvic oligophrenia has been shown to involve a specific enzyme deficiency. One of the two proteins required for the conversion of phenylalanine to tyrosine is lacking in livers of patients with the disease. The second protein, which occurs in other tissues as well as in liver, is not deficient in the disease (H. W. Wallace, K. Moldave, and A. Meister, Proc. Soc. Exptl. Biol. Med. 64, 632 (1957) C. Mitoma, R. M. Auld, and S. Udenfriend, ibid. 64, 634 (1957)). 

Block in phenylpyruvic oligophrenia. 2. Block in tyrosinosis. 3. Block in alcaptonuria. 4. Impairment in ascorbic acid deficiency. 

In the hereditary disease phenylpyruvic oligophrenia there appears to be an inability to convert phenylalanine to tyrosine, which results in an accumulation of phenylalanine in the blood, and the excretion of phenylalanine, phenylpyruvic acid, and phenyllactic acid. ... 

Goldstein, F. B. Studies on aromatic acids in relation to phenylpyruvic oligophrenia. Thesis, McGill University, Montreal (1955). 

Much of the earlier knowledge of the metabolic pathways of phenylalanine and tyrosine was obtained by the study of the defects in the hereditary diseases, alcaptonuria, albinism, phenylpyruvic oligophrenia, and tyrosinosis. Widespread interest in this subject dates from the publication of Garrod s Inborn Errors of Metabolism (2). The metabolic Uoeka at particular steps in the degradative pathways of phenylalanine and tyrosine for the disorders mentioned above are shown in Fig. 15. 

Fio. 15. Metabolic pathways of phenylalanine and tyrosine. The numbered dashed lines have the following significance 1 block in phenylpyruvic oligophrenia 2 — block in tyrosinosis 3 block in alcaptonuria 4 = impairment in ascorbic acid deficiency. 

It has for some time been apparent from nutritional and tracer studies, and from investigation of the metabolic error, phenylpyruvic oligophrenia, that tyrosine is formed in animals by enzymic hydroxyl-ation of phenylalanine (see 1 ) (Fig. 2). Partial characterization of the enzjmiic system which catalyzes this transformation is reported by Udenfriend and by Mitoma (556,557,768,770). 

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