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1H nuclear magnetic resonance (NMR) was used to detect directly the signal from the aromatic protons of phenylalanine (phe) in the brains of rabbits made hyperphenylalaninemic by administration of a diet high in phe and containing 0.4% alpha-methylphenylalanine. In addition to those resonances found in the region between 6.5 and 8.5 ppm in the 1H NMR spectra of control rabbits, a resonance centered at 7.37 ppm was observed in the spectra obtained from the brains of hyperphenylalaninemic rabbits in vivo or in situ postmortem. The chemical shift of this additional resonance was that expected for protons of the phenyl ring of phe. Its intensity correlated well with measurements of brain phe levels made on postmortem samples by amino acid analyzer. Both of these measurements correlated poorly with amino acid analyzer measurements of serum phe, especially at high values of the latter. High-resolution 1H NMR spectra of the brain extracts showed that in most animals an unidentified aromatic compound, possibly gamma-glutamyl-phe, was present in addition to phe. This study demonstrates the feasibility of measuring the concentration of brain phenyl and its metabolites noninvasively by 1H NMR. The method can be used for similar measurements in human brain.

Proton NMR Observation of Phenylalanine and an Aromatic Metabolite in the Rabbit Brain in Vivo