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. 1994 Sep 1;302(Pt 2):601–610. doi: 10.1042/bj3020601

The effect of elevated plasma phenylalanine levels on protein synthesis rates in adult rat brain.

D S Dunlop 1, X R Yang 1, A Lajtha 1
PMCID: PMC1137270  PMID: 8093014

Abstract

Increasing the plasma phenylalanine concentration to levels as high as 0.560-0.870 mM (over ten times normal levels) had no detectable effect on the rate of brain protein synthesis in adult rats. The average rates for 7-week-old rats were: valine, 0.58 +/- 0.05%/h, phenylalanine, 0.59 +/- 0.06%/h, and tyrosine, 0.60 +/- 0.09%/h, or 0.59 +/- 0.06%/h overall. Synthesis rates calculated on the basis of the specific activity of the tRNA-bound amino acid were slightly lower (4% lower for phenylalanine) than those based on the brain free amino acid pool. Similarly, the specific activities of valine and phenylalanine in microdialysis fluid from striatum were practically the same as those in the brain free amino acid pool. Thus the specific activities of the valine and phenylalanine brain free pools are good measures of the precursor specific activity for protein synthesis. In any event, synthesis rates, whether based on the specific activities of the amino acids in the brain free pool or those bound to tRNA, were unaffected by elevated levels of plasma phenylalanine. Brain protein synthesis rates measured after the administration of quite large doses of phenylalanine (> 1.5 mumol/g) or valine (15 mumol/g) were in agreement (0.62 +/- 0.01 and 0.65 +/- 0.01%/h respectively) with the rates determined with infusions of trace amounts of amino acids. Thus the technique of stabilizing precursor-specific activity, and pushing values in the brain close to those of the plasma, by the administration of large quantities of precursor, appears to be valid.

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Selected References

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  1. Agrawal H. C., Bone A. H., Davison A. N. Effect of phenylalanine on protein synthesis in the developing rat brain. Biochem J. 1970 Apr;117(2):325–331. doi: 10.1042/bj1170325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antonas K. N., Coulson W. F. Brain uptake and protein incorporation of amino acids studied in rats subjected to prolonged hyperphenylalaninaemia. J Neurochem. 1975 Sep;25(3):309–314. doi: 10.1111/j.1471-4159.1975.tb06972.x. [DOI] [PubMed] [Google Scholar]
  3. Aoki K., Siegel F. L. Hyperphenylalaninemia: disaggregation of brain polyribosomes in young rats. Science. 1970 Apr 3;168(3927):129–130. doi: 10.1126/science.168.3927.129. [DOI] [PubMed] [Google Scholar]
  4. Benson J. R., Hare P. E. O-phthalaldehyde: fluorogenic detection of primary amines in the picomole range. Comparison with fluorescamine and ninhydrin. Proc Natl Acad Sci U S A. 1975 Feb;72(2):619–622. doi: 10.1073/pnas.72.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Binek-Singer P., Johnson T. C. The effects of chronic hyperphenylalaninaemia on mouse brain protein synthesis can be prevented by other amino acids. Biochem J. 1982 Aug 15;206(2):407–414. doi: 10.1042/bj2060407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Butcher S. P., Hamberger A. In vivo studies on the extracellular, and veratrine-releasable, pools of endogenous amino acids in the rat striatum: effects of corticostriatal deafferentation and kainic acid lesion. J Neurochem. 1987 Mar;48(3):713–721. doi: 10.1111/j.1471-4159.1987.tb05575.x. [DOI] [PubMed] [Google Scholar]
  7. Cornish-Bowden A. The amino acid compositions of proteins are correlated with their molecular sizes. Biochem J. 1983 Jul 1;213(1):271–274. doi: 10.1042/bj2130271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dunlop D. S., van Elden W., Lajtha A. A method for measuring brain protein synthesis rates in young and adult rats. J Neurochem. 1975 Feb;24(2):337–344. doi: 10.1111/j.1471-4159.1975.tb11885.x. [DOI] [PubMed] [Google Scholar]
  9. Dunlop D. S., van Elden W., Lajtha A. Optimal conditions for protein synthesis in incubated slices of rat brain. Brain Res. 1975 Dec 5;99(2):303–318. doi: 10.1016/0006-8993(75)90031-1. [DOI] [PubMed] [Google Scholar]
  10. Garlick P. J., Marshall I. A technique for measuring brain protein synthesis. J Neurochem. 1972 Mar;19(3):577–583. doi: 10.1111/j.1471-4159.1972.tb01375.x. [DOI] [PubMed] [Google Scholar]
  11. Garlick P. J., McNurlan M. A., Preedy V. R. A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H]phenylalanine. Biochem J. 1980 Nov 15;192(2):719–723. doi: 10.1042/bj1920719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldspink D. F. Protein turnover and growth of the rat brain from the foetus to old age. J Neurochem. 1988 May;50(5):1364–1368. doi: 10.1111/j.1471-4159.1988.tb03017.x. [DOI] [PubMed] [Google Scholar]
  13. Hargreaves-Wall K. M., Buciak J. L., Pardridge W. M. Measurement of free intracellular and transfer RNA amino acid specific activity and protein synthesis in rat brain in vivo. J Cereb Blood Flow Metab. 1990 Mar;10(2):162–169. doi: 10.1038/jcbfm.1990.31. [DOI] [PubMed] [Google Scholar]
  14. Hughes J. V., Johnson T. C. Hyperphenylalanemia: effect on brain polyribosomes can be partially reversed by other amino acids. Science. 1977 Jan 28;195(4276):402–404. doi: 10.1126/science.831283. [DOI] [PubMed] [Google Scholar]
  15. Keen R. E., Barrio J. R., Huang S. C., Hawkins R. A., Phelps M. E. In vivo cerebral protein synthesis rates with leucyl-transfer RNA used as a precursor pool: determination of biochemical parameters to structure tracer kinetic models for positron emission tomography. J Cereb Blood Flow Metab. 1989 Aug;9(4):429–445. doi: 10.1038/jcbfm.1989.67. [DOI] [PubMed] [Google Scholar]
  16. Neidle A., Banay-Schwartz M., Sacks S., Dunlop D. S. Amino acid analysis using 1-naphthylisocyanate as a precolumn high performance liquid chromatography derivatization reagent. Anal Biochem. 1989 Aug 1;180(2):291–297. doi: 10.1016/0003-2697(89)90433-8. [DOI] [PubMed] [Google Scholar]
  17. Pitts F. N., Jr, Quick C. Brain succinate semialdehyde. II. Changes in the developing rat brain. J Neurochem. 1967 May;14(5):561–570. doi: 10.1111/j.1471-4159.1967.tb09556.x. [DOI] [PubMed] [Google Scholar]
  18. Smith C. B., Deibler G. E., Eng N., Schmidt K., Sokoloff L. Measurement of local cerebral protein synthesis in vivo: influence of recycling of amino acids derived from protein degradation. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9341–9345. doi: 10.1073/pnas.85.23.9341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith C. B., Sun Y., Deibler G. E., Sokoloff L. Effect of loading doses of L-valine on relative contributions of valine derived from protein degradation and plasma to the precursor pool for protein synthesis in rat brain. J Neurochem. 1991 Nov;57(5):1540–1547. doi: 10.1111/j.1471-4159.1991.tb06349.x. [DOI] [PubMed] [Google Scholar]
  20. Smith C. B. The measurement of regional rates of cerebral protein synthesis in vivo. Neurochem Res. 1991 Sep;16(9):1037–1046. doi: 10.1007/BF00965848. [DOI] [PubMed] [Google Scholar]
  21. Sun Y., Deibler G. E., Sokoloff L., Smith C. B. Determination of regional rates of cerebral protein synthesis adjusted for regional differences in recycling of leucine derived from protein degradation into the precursor pool in conscious adult rats. J Neurochem. 1992 Sep;59(3):863–873. doi: 10.1111/j.1471-4159.1992.tb08324.x. [DOI] [PubMed] [Google Scholar]
  22. Wall K. M., Pardridge W. M. Decreases in brain protein synthesis elicited by moderate increases in plasma phenylalanine. Biochem Biophys Res Commun. 1990 May 16;168(3):1177–1183. doi: 10.1016/0006-291x(90)91153-j. [DOI] [PubMed] [Google Scholar]
  23. Wallyn C. S., Vidrich A., Airhart J., Khairallah E. A. Analysis of the specific radioactivity of valine isolated from aminoacyl-transfer ribonucleic acid of rat liver. Biochem J. 1974 Jun;140(3):545–548. doi: 10.1042/bj1400545. [DOI] [PMC free article] [PubMed] [Google Scholar]

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