Tyrosinase phenylketonuria

Enzyme deficiency diseases. A variety of metabolic diseases are caused by deficiencies or malfunctions of enzymes, due originally to gene mutation. Albinism, for example, may be caused by the absence of tyrosinase, an enzyme essential for the production of cellular pigments. The hereditary lack of phenylalanine hydroxylase results in the disease phenylketonuria (PKU) PKU is usually managed by dietary modifications, but intravenous... 

The absence of pigmentation associated Avith phenylketonuria may be due either to lack of tyrosine as substrate for melanin formation, or to inhibition of tyrosinase by the abnormal amounts of phenylalanine (179a), or to both. Pigmentation is restored on giving tyrosine (816a). 

Parahydroxyphenylpyruvic, phenylacetic, and phenyllactic acids inhibit tyrosinase, but whereas the first of these compounds is a potent inhibitor, the others are only weak inhibitors. It seems that if this inhibitory effect were important in phenylketonuria, pigment metabolism would be more apparently altered in tyrosinosis than in phenylketonuria, which seems not to be the case. However, the enzyme block might explain why small doses or dietary amounts of tyrosine have no effect on the pigmentation of patients with phenylketonuria. Only when large doses of the amino acid are administered are pigmentation and epinephrine biosynthesis restored to normal, probably because tyrosine competes with phenylalanine metabolites for melanocyte tyrosinase and dopa decarboxylase. 

Miyamato, M. and Fitzpatrick, Th. B., Competitive inhibition of mammalian tyrosinase by phenylalanine and its relationship to hair pigmentation in phenylketonuria, Nature 179, 199 (1957). 

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