Accumulation of a Tetrahydroisoquinoline in Phenylketonuria

Abstract

3',4'-Deoxynorlaudanosolinecarboxylic acid (DNLCA), a tetrahydroisoquinoline derived from dopamine and phenylpyruvic acid, has been detected by computerized mass fragmentography in urine of phenylketonuric children and in urine and brain of rats with experimentally induced hyperphenylalaninemia. Levels of DNLCA in brain of treated animals were more than tenfold higher than controls, and the excess tetrahydroisoquinoline appeared to accumulate in the cerebellum and cortex. DNLCA is a noncompetitive inhibitor of dopamine beta-hydroxylase (inhibition constant, Ki, = 0.42 mM) and is taken up by the brain.