Effects of l-phenylalanine and sodium phenylpyruvate on the formation of adrenaline from l-tyrosine in adrenal medulla in vitro

Abstract

Incubation of slices of guinea-pig adrenal medulla with L-[2-Cl4] tyrosine in well-oxygenated modified Ringer solution results in the formation of labelled [beta]-hydroxytyramine and epinephrine. The addition of 0.1 mM-sodium phenylpyruvate in vitro causes a 50% decrease in the recovery of labelled epinephrine. This decrease is caused by inhibition of the synthesis of epinephrine, rather than by its degradation after synthesis. Whereas, usually, no labelled dihydroxyphenylalanine (dopa) is observed during the incubation of slices of guinea-pig adrenal medulla in the presence of labelled tyrosine, the addition of sodium phenylpyruvate results in the appearance of labelled dopa. This effect indicates that dopa decarboxy-lation is inhibited by sodium phenylpyruvate. It is concluded that inhibition of epinephrine biosynthesis by sodium phenylpyruvate is largely due to inhibition of dopa decarboxylase. The addition of L-phenylalanine in vitro has no effect on the synthesis of epinephrine. The bearing of these results on the mental abnormalities associated with phenylketonuria are discussed.