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Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo
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Phenylketonuria: High plasma phenylalanine decreases cerebral protein synthesis

Marieke Hoeksma1, Dirk-Jan Reijngoud, Jan Pruim

  • 1Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Section of Metabolic Diseases, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.

Molecular Genetics and Metabolism
|February 10, 2009
PubMed

Insights

Phenylketonuria (PKU) treatment may need to continue into adulthood. High phenylalanine levels in adults with PKU significantly decrease brain protein synthesis rates, impacting cognitive function.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Medical Genetics

Background:

  • Phenylketonuria (PKU) is a genetic disorder characterized by high phenylalanine levels.
  • Untreated PKU leads to severe intellectual disability.
  • The necessity of lifelong dietary phenylalanine restriction in PKU is not fully understood.

Purpose of the Study:

  • To investigate the relationship between plasma phenylalanine concentrations and cerebral protein synthesis rates in adult PKU patients.
  • To explore the in-vivo pathophysiological mechanisms linking phenylalanine levels to brain function.

Main Methods:

  • Utilized positron emission tomography (PET) brain imaging.
  • Administered an intravenous l-[1-(11)C]-tyrosine bolus to 19 adult PKU patients.
  • Correlated plasma phenylalanine concentrations with measured cerebral protein synthesis rates.

Main Results:

  • A significant negative correlation (R(2)=0.40, p<0.01) was observed between plasma phenylalanine levels and cerebral protein synthesis rate.
  • Cerebral protein synthesis was notably reduced in PKU patients with phenylalanine concentrations above 600-800 micromol/l.
  • These findings indicate impaired cerebral protein metabolism at elevated phenylalanine levels.

Conclusions:

  • High plasma phenylalanine concentrations negatively impact cerebral protein synthesis in adults with PKU.
  • These results suggest that maintaining phenylalanine levels below 600-800 micromol/l is crucial for adult PKU patients.
  • Lifelong dietary management of PKU may be necessary to prevent adverse neurological outcomes.

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