Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis

In phenylketonuria, elevated plasma phenylalanine concentrations may disturb blood-to-brain large neutral amino acid (LNAA) transport and cerebral protein synthesis (CPS). We investigated the associations between these processes, using data obtained by positron emission tomography with L-[1-C-11]-tyrosine (C-11-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for C-11-Tyr transport from arterial plasma to brain tissue (K-1), while CPS was modeled by the rate constant for C-11-Tyr incorporation into cerebral protein (k(3)). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOls): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k(3) and each predictor variable were analyzed by multiple linear regression. The rate constant k(3) was inversely associated with brain phenylalanine concentrations in VOls 2 and 3 (adjusted R-2 = 0.826, F = 19.936, P = 0.021). Since brain phenylalanine concentrations in these VOls highly correlated with each other, the specific associations of each predictor with k(3) could not be determined. The associations between k(3) and plasma phenylalanine concentration, K-1, and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k(3) and increased brain phenylalanine concentrations