Phenylketonuria: Brain Phenylalanine Concentrations Relate Inversely to Cerebral Protein Synthesis

Author:

de Groot Martijn J12,Sijens Paul E3,Reijngoud Dirk-Jan24,Paans Anne M5,van Spronsen Francjan J12

Affiliation:

1. Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

2. Department of Digestive and Metabolic Diseases, Center for Liver, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

3. Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

4. Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

5. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Abstract

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-[1-11C]-tyrosine (11C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for 11C-Tyr transport from arterial plasma to brain tissue (K1), while CPS was modeled by the rate constant for 11C-Tyr incorporation into cerebral protein (k3). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOIs): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k3 and each predictor variable were analyzed by multiple linear regression. The rate constant k3 was inversely associated with brain phenylalanine concentrations in VOIs 2 and 3 (adjusted R2=0.826, F=19.936, P=0.021). Since brain phenylalanine concentrations in these VOIs highly correlated with each other, the specific associations of each predictor with k3 could not be determined. The associations between k3 and plasma phenylalanine concentration, K1, and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k3 and increased brain phenylalanine concentrations.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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