Summary
Phenylketonuria is an autosomal recessive inherited disease caused by a disturbance in the phenylalanine hydroxylating system. Phenylalanine is converted to tyrosine by phenylalanine hydroxylase, which is located mainly in the liver. This enzyme needs the reduced cofactor tetrahydrobiopterin to be active. In phenylketonuria, low or zero enzyme activity is measured. Enzyme activity higher than 5% compared with that in normal controls is correlated to hyperphenylalaninemia. Dihydropteridine reductase regenerates the active cofactor. A defect in this enzyme or in the biosynthesis of the cofactor results in phenylketonuria which does not respond to dietary treatment because the biosynthesis of neurotransmitters is impaired.
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Bartholomé, K.: A new molecular defect in phenylketonuria. Lancet 1974II, 1580
Bartholomé, K., Lutz, P., Bickel, H.: Determination of phenylalanine hydroxylase activity in patients with phenylketonuria and hyperphenylalaninemia. Pediatr. Res. 9, 899–903 (1975)
Bartholomé, K., Byrd, D. J.: L-DOPA and 5-hydroxytryptophan therapy in phenylketonuria with normal phenylalanine hydroxylase activity. Lancet 1975II, 1042
Bartholomé, K., Byrd, D. J., Kaufman, S., Milstien, S.: Atypical phenylketonuria with normal phenylalanine hydroxylase reductase activity in vitro. Pediatrics 59, 757–761 (1977)
Bickel, H., Gerrard, J., Hickmans, E. M.: Influence of phenylalanine intake on phenylketonuria. Lancet 1953II, 812–815
Blaskovics, M. E., Nelson, T. L.: Phenylketonuria and its variations. Calif. Med. 115, 42 (1971)
Cotton, R. G. H., Grattan, P. J.: Phenylalanine hydroxylase of Macaca irus. Eur. J. Biochem. 60, 427–430 (1975)
Dancis, J., Hutzler, J., Snyderman, S. E., Cox, R. P.: Enzyme activity in classical and variant forms of maple syrup urine disease. J. Pediatr. 81, 312–320 (1972)
Fölling, A.: Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität. Hoppe-Seylers Z. Physiol. Chem. 227, 169 (1934)
Guthrie, R.: Blood screening for phenylketonuria. JAMA 178, 863 (1961)
Grimm, U., Knapp, A., Schlenzka, K., Hesse, R.: Phenylalaninhydroxylase-Aktivität bei heterozygoten Anlageträgern für das Phenylketonurie-Gen. Acta Biol. Med. Germ. 36, 1179–1182 (1977)
Huang, C. Y., Kaufman, S.: Studies on the mechanisms of action of phenylalanine hydroxylase and its protein stimulator. J. Biol. Chem. 248, 4242–4251 (1973)
Jervis, G. A.: The genetics of phenylpyruvic oligophrenia. J. Ment. Sci. 85, 719–762 (1939)
Jervis, G. A.: Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc. Soc. Exp. Biol. 82, 514–515 (1953)
Justice, P., O'Flynn, M. E., Hsia, D. Y. Y.: Phenylalanine hydroxylase activity in hyperphenylalaninemia. Lancet 1967I, 928–929
Kang, E. S., Kaufman, S., Gerald, P. S.: Clinical and biochemical observations of patients with atypical phenylketonuria. Pediatrics 45, 83–92 (1970)
Kaufman, S.: The enzymatic conversion of phenylalanine to tyrosine. J. Biol. Chem. 226, 511–524 (1957)
Kaufman, S.: A new cofactor required for the enzymatic conversion of phenylalanine to tyrosine. J. Biol. Chem. 230, 931–939 (1958)
Kaufman, S.: Metabolism of the phenylalanine hydroxylation cofactor. J. Biol. Chem. 242, 3934–3943 (1967)
Kaufman, S., Fisher, D. B.: Purification and some physical properties of phenylalanine hydroxylase from rat liver. J. Biol. Chem. 245, 4745–4750 (1970)
Kaufman, S., Max, E. E., Kang, E. S.: Phenylalanine hydroxylase activity in liver biopsies from hyperphenylalaninemia heterozygotes: Deviation from proportionality with gene dosage. Pediatr. Res. 9, 632–634 (1975a)
Kaufman, S., Holtzman, N. A., Milstien, S., Butler, I. J., Krumholz, A.: Phenylketonuria due to a deficiency of dihydropteridine reductase. N. Engl. J. Med. 293, 785–790 (1975b)
Menkes, J. H.: A proposed classification for the hyperphenylalaninemias. In: Proceedings of the International Conference on Inborn Errors of Metabolism, Dubrovnik, Yugoslavia, p. 29. Washington: Children's Bureau, U.S. Dept. of Health, Education and Welfare 1967
Mitoma, C.: Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. Biophys. 60, 476–484 (1956)
Niederwieser, A., Curtius, H.-C., Bettoni, O., Bieri, J., Schirks, B., Viscontini, M., Schaub, J.: Atypical phenylketonuria caused by 7,8-dihydrobiopterin synthetase deficiency. Lancet 1979I, 131–133
Smith, I.: Atypical phenylketonuria accompanied by a severe progressive neurological illness unresponsive to dietary treatment. Arch. Dis. Child. 49, 245 (1974)
Woo, S. L. C., Gillam, S. S., Woolf, L. I.: The isolation and properties of phenylalanine hydroxylase from human liver. Biochem. J. 139, 741–749 (1974)
Woolf, L. I., Goodwin, B. L., Cranston, W. I., Wade, D. N., Woolf, F., Hudson, F. P., McBean, M. S.: A third allele at the phenylalanine-hydroxylase locus in mild phenylketonuria (hyperphenylalaninaemia). Lancet 1968I, 114–117
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Bartholomé, K. Genetics and biochemistry of the phenylketonuria-present state. Hum Genet 51, 241–245 (1979). https://doi.org/10.1007/BF00283389
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DOI: https://doi.org/10.1007/BF00283389