Woolf Li

The isolation and properties of phenylalanine hydroxylase from human liver

Phenylalanine hydroxylase was prepared from human foetal liver and purified 800-fold; it appeared to be essentially pure. The phenylalanine hydroxylase activity of the liver was confined to a single protein of mol.wt. approx. 108000, but omission of a preliminary filtration step resulted in partial conversion into a second enzymically active protein of mol.wt. approx. 250000. Human adult and full-term infant liver also contained a single phenylalanine hydroxylase with molecular weights and kinetic parameters the same as those of the foetal enzyme; foetal, newborn and adult phenylalanine hydroxylase are probably identical. The K(m) values for phenylalanine and cofactor were respectively one-quarter and twice those found for rat liver phenylalanine hydroxylase. As with the rat enzyme, human phenylalanine hydroxylase acted also on p-fluorophenylalanine, which was inhibitory at high concentrations, and p-chlorophenylalanine acted as an inhibitor competing with phenylalanine. Iron-chelating and copper-chelating agents inhibited human phenylalanine hydroxylase. Thiol-binding reagents inhibited the enzyme but, as with the rat enzyme, phenylalanine both stabilized the human enzyme and offered some protection against these inhibitors. It is hoped that isolation of the normal enzyme will further the study of phenylketonuria.

Conference on sex ratio in phenylketonuria

Summary A conference was held to discuss the significance of the disproportionate sex ratio (2:1) observed in the Collaborative Study of Children Treated for Phenylketonuria. No definite conclusions were arrived at concerning the cause of this observation, but it was felt that the present screening programs are sound and are not missing significant numbers of children with phenylketonuria. If the observation of an altered sex ratio has not occurred by chance in the PKU Collaborative Study, this could be the result of the criteria for inclusion in the Collaborative Study or of a slight variation in how the sexes metabolize phenylalanine.