Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis

In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synt...

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Published in:Orphanet journal of rare diseases 2013-09, Vol.8 (1), p.133-133, Article 133
Main Authors: de Groot, Martijn J, Hoeksma, Marieke, Reijngoud, Dirk-Jan, de Valk, Harold W, Paans, Anne M J, Sauer, Pieter J J, van Spronsen, Francjan J
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Biological Transport - physiology
Brain
Brain - metabolism
Carbon Radioisotopes - metabolism
Female
Health aspects
Humans
Intellectual disabilities
Linear Models
Male
Medical research
Medicine, Experimental
Metabolic disorders
Middle Aged
PET imaging
Phenylketonuria
Phenylketonurias - metabolism
Physiological aspects
Protein biosynthesis
Protein synthesis
Rare diseases
Studies
Tyrosine
Tyrosine - metabolism
Young Adult
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Summary:In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synthesis. In this study, we investigated the hypothesis that impaired LNAA influx relates to reduced cerebral protein synthesis. Using positron emission tomography, L-[1-11C]-tyrosine (11C-Tyr) brain influx and incorporation into cerebral protein were studied in 16 PKU patients (median age 24, range 16 - 47 years), most of whom were early and continuously treated. Data were analyzed by regression analyses, using either 11C-Tyr brain influx or 11C-Tyr cerebral protein incorporation as outcome variable. Predictor variables were baseline plasma Phe concentration, Phe tolerance, age, and 11C-Tyr brain efflux. For the modelling of cerebral protein incorporation, 11C-Tyr brain influx was added as a predictor variable. 11C-Tyr brain influx was inversely associated with plasma Phe concentrations (median 512, range 233 - 1362 μmol/L; delta adjusted R2=0.571, p=0.013). In addition, 11C-Tyr brain influx was positively associated with 11C-Tyr brain efflux (delta adjusted R2=0.098, p=0.041). Cerebral protein incorporation was positively associated with 11C-Tyr brain influx (adjusted R2=0.567, p
ISSN:1750-1172
1750-1172
DOI:10.1186/1750-1172-8-133