Abstract
A gas chromatographic-mass spectrometric method was developed for analyzing phenylalanine and tyrosine (Tyr) in plasma and brain. With this procedure, we were able to show that18O2 is incorporated into Tyr in vivo and that the presence of18O-Tyr in plasma is a relative measure of phenylalanine hydroxylating activity. Treatment withp-chlorophenylalanine decreases the18O incorporation into Tyr. Because of the simplicity of the procedure and its easy adaptability to human studies, the incorporation of18O2 into endogenous constituents might serve as a useful diagnostic procedure for some metabolic disorders, such as phenylketonuria. These results also indicate that labeling with18O cannot be used to measure the turnover rate of brain catecholamines as previously proposed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jervis, G. A. 1953. Phenylpyruvic oligophrenic deficiency of phenylalanine-oxidizing system. Proc. Soc. Exp. Biol. Med. 82:514–515.
Hsia, D. Y.-Y. 1966. Inborn Errors of Metabolism, Part 1, Clinical Aspects, 2nd Ed., Year Book Medical Publishers, Chicago, pp. 6–8, 134–143.
Lipton, M. A., Gordon, R., Guroff, G., andUdenfriend, S. 1967.p-Chlorophenylalanine-induced chemical manifestations of phenylketonuria in rats. Science 156:248–250.
Sedvall, G., Mayevsky, A., Fri, C. G., Sjoqvist, B., andSamuel, D. 1973. The use of stable isotopes for labeling homovanillic acid in rat brainin vivo. Pages 57–68,in Costa, E., andHolmstedt, B. (eds.), Advances in Biochemical Psychopharmacology, Vol. 7, Raven Press, New York.
Koe, B. K., andWeissman, A. 1966.p-Chlorophenylalanine: A specific depletor of brain serotonin. J. Pharmacol. Exp. Ther. 154:499–516.
Ter-Pogossian, M. M., Eichling, J. O., Davis, D. O., Welch, M. J., andMetzger, J. M. 1969. The determination of regional cerebral blood flow by means of water labeled with radioactive oxygen 15. Radiology 93:31–40.
McGee, M. M., Greengard, O., andKnox, W. E. 1972. Liver phenylalanine hydroxylase activity in relation to blood concentrations of tyrosine and phenylalanine in the rat. Biochem. J. 127:675–680.
Brand, L. M., andHarper, A. E. 1974. Effect of glucagon on phenylalanine metabolism and phenylalanine degrading enzymes in the rat. Biochem. J. 142:231–245.
Milstien, S., andKaufman, S. 1975. Studies on the phenylalanine hydroxylase system in vivo: An in vivo assay based on the liberation of deuterium or tritium into the body water from ring-labeledl-phenylalanine. J. Biol. Chem. 250:4782–4785.
Nagatsu, T., Levitt, M., andUdenfriend, S. 1964. Tyrosine hydroxylase: The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239:2910–2917.
Neff, N. H., Galli, C. L., andCosta, E. 1976 The turnover of dopamine: Studies with18O2. Pages 187–192,in Costa, E., andGessa, G. L. (eds.), Advances in Biochemical Psychopharmacology, Vol. 16, Raven Press, New York.
Mayevsky, A., Sjoqvist, B., Fri, C.-G., Samuel, D. andSedvall, G. 1973. Incorporation of18O into homovallic acid of rat brain during exposure to oxygen-18-containing atmosphere. Biochem. Biophys. Res. Commun. 51:746–755.
Costa, E., Koslow, S. H., andLeFevre, H. F. 1975. Mass fragmentography: A tool for studying transmitter function at synaptic level. Pages 1–24,in Iversen, L., Iversen, S., andSnyder, S. H. (eds.), Handbook of Psychopharmacology, Vol. 1, Plenum, New York.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galli, C.L., Commissiong, J.W., Karoum, F. et al. Measurement of phenylalanine hydroxylating activity in vivo. Neurochem Res 2, 657–669 (1977). https://doi.org/10.1007/BF00963778
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00963778