title: Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis.
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-(11)C]-tyrosine ((11)C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for (11)C-Tyr transport from arterial plasma to brain tissue (K1), while CPS was modeled by the rate constant for (11)C-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 R(2)=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.
authors.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.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: de Groot
authors.affiliation: Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sijens
authors.affiliation: 1] Department of Digestive and Metabolic Diseases, Center for Liver, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands [2] Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Reijngoud
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Paans
authors.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.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood*; D049268:Positron-Emission Tomography; D014176:Protein Biosynthesis; D011859:Radiography
chemical_list: D010649:Phenylalanine