Abstract
THE molecular defect in classical phenylketonuria (PKU) has not been elucidated, but it seems certain that the block in metabolism is in the conversion of phenylalanine to tyrosine1 and that the enzyme which carries out this reaction, phenylalanine hydroxylase (EC, 1.14.3.1), is defective2. Progress in delineating the molecular defect has been slow because of the limited tissue distribution of phenylalanine hydroxylase, lability of this enzyme after death3, scarcity of normal and PKU livers for study and the nonspecific purification methods for this enzyme. We recently developed a specific, one-step method for purification of phenylalanine hydroxylase from crude extracts of monkey liver4, and have now applied it to crude extracts of livers from two human foetuses, from three patients who died of unrelated disease and from a patient with classical PKU who died at 12 yr. (The PKU patient did not follow the rapidly progressive course described recently in variant forms of PKU5 and dihydropteridine reductase activity was demonstrated in the liver.)
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COTTON, R., DANKS, D. Purification of inactive phenylalanine hydroxylase protein from liver in classical phenylketonuria. Nature 260, 63–64 (1976). https://doi.org/10.1038/260063a0
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DOI: https://doi.org/10.1038/260063a0
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