Skip to main content
SpringerLink
Log in

Abnormal amino acid metabolism and brain protein synthesis during neural development

  • Overview
  • Published:
Neurochemical Research Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Garrod, A. E. 1908. Inborn errors of metabolism. Lancet 2:1–7.

    Google Scholar 

  2. Popjak, G. 1975. Role of biochemistry in research on mental retardation. Pages 507–516,in Buchwald, N. A., and Brazier, M. A. B. (eds.), Brain Mechanisms in Mental Retardation, Academic Press, New York.

    Google Scholar 

  3. Brady, R. O. 1976. Inherited metabolic diseases of the nervous system. Science 193:733–739.

    Google Scholar 

  4. Scriver, C. R. 1969. Inborn errors of amino acid metabolism. Br. Med. Bull. 25:35–41.

    Google Scholar 

  5. Nyhan, W. L. 1974. Heritable Disorders of Amino Acid Metabolism: Patterns of Clinical Expression and Genetic Variation, John Wiley, New York.

    Google Scholar 

  6. Wiltse, H. E., andMenkes, J. H 1972. Brain damage in the aminoacidurias. Pages 143–167,in Lajtha, A. (ed.), Handbook of Neurochemistry, Vol. VII, Pathological Chemistry of the Nervous System, Plenum Press, New York.

    Google Scholar 

  7. Gaull, G. E. 1972. Abnormal metabolism of sulfur-containing amino acids associated with brain dysfunction. Pages 169–190,in Lajtha, A. (ed.), Handbook of Neurochemistry, Vol. VII, Pathological Chemistry of the Nervous System, Plenum Press, New York.

    Google Scholar 

  8. Guroff, G., King, W., andUdenfriend, S. 1961. The uptake of tyrosine by rat brain in vitro. J. Biol. Chem. 236:1773–1777.

    Google Scholar 

  9. Appel, S. H. 1966. Inhibition of brain protein synthesis: An approach to the biochemical basis of neurological dysfunction in the aminoacidurias. Trans. N.Y. Acad. Sci. 29:63–69.

    Google Scholar 

  10. Appel, S. H. 1970. Inhibition of brain protein synthesis. Pages 621–630,in Lajtha, A. (ed.), Protein Metabolism of the Nervous System, Plenum Press, New York.

    Google Scholar 

  11. Hughes, J. V., andJohnson, T. C. 1976. The effects of phenylalanine on amino acid metabolism and protein synthesis in brain cells in vitro. J. Neurochem. 26:1105–1113.

    Google Scholar 

  12. Fellman, J. H. 1956. Inhibition of DOPA decarboxylase by aromatic acids associated with phenylpyruvic oligophrenia. Proc. Soc. Exp. Biol. Med. 93:413–414.

    Google Scholar 

  13. Hanson, A. 1959. Action of phenylalanine metabolites on glutamic acid decarboxylase and γ-amino butyric acid-α-ketoglutaric acid transaminase in brain. Acta Chem. Scand. 13:1366–1374.

    Google Scholar 

  14. Tashian, R. E. 1961. Inhibition of brain glutamic acid decarboxylase by phenylalanine, valine and leucine derivatives: A suggestion concerning the etiology of the neurological defect in phenylketonuria and branched-chain ketonuria. Metabolism 10:393–402.

    Google Scholar 

  15. Yuwiler, A., andGeller, E. 1969. Brain serotonin changes in phenylalanine-fed rats: Synthesis, storage and degradation. J. Neurochem. 16:999–1005.

    Google Scholar 

  16. Shah, S. N., Peterson, N. A., andMcKean, C. M. 1972. Impaired myelin formation in experimental hyperphenylalaninaemia. J. Neurochem. 19:479–485.

    Google Scholar 

  17. Menkes, J. H. 1968. Cerebral proteolipids in phenylketonuria. Neurology 18:1003–1008.

    Google Scholar 

  18. Menkes, J. H., Hurst, P. L., andCraig, J. M. 1954. A new syndrome: Progressive familial cerebral dysfunction with an unusual urinary substance. Pediatrics 14:462–466.

    Google Scholar 

  19. Dancis, J., Hutzler, J., andLevitz, M. 1963. The diagnosis of maple syrup urine disease (branched chain ketoaciduria) by the in vitro study of the peripheral leukocyte. Pediatrics 32:234–238.

    Google Scholar 

  20. Dancis, J., Hutzler, J., andLevitz, M. 1965. Detection of the heterozygote in maple syrup urine disease. J. Pediatr. 66:595–603.

    Google Scholar 

  21. Dancis, J., Hutzler, J., andCox, R. P. 1969. Enzyme defect in skin fibroblasts in intermittent branched-chain ketonuria and in maple syrup urine disease. Biochem. Med. 2:407–411.

    Google Scholar 

  22. Menkes, J. H., Philippart, M. andFiol, R. E. 1965. Cerebral lipids in maple syrup disease. J. Pediatr. 66:584–594.

    Google Scholar 

  23. Prensky, A. L., andMoser, H. W., 1966. Brain lipids, proteolipids, and free amino acids in maple syrup urine disease. J. Neurochem. 13:863–874.

    Google Scholar 

  24. Menkes, J. H., andSolcher, H., 1967. Maple syrup urine disease: Effects of dietary therapy on cerebral lipids. Arch. Neurol. 16:486–491.

    Google Scholar 

  25. Ladu, B. N., Howell, R. R., Jacoby, G. A., Seegmiller, J. E., andZanroni, V. G. 1962. The enzymatic defect in histidinemia. Biochem. Biophys. Res. Commun. 7:398–402.

    Google Scholar 

  26. Ladu, B. N., Howell, R. R., Jacoby, G. A., Seegmiller, J. E., Sober, E. K., Zanroni, V. G., Canby, J. P., andZiegler, L. K. 1963. Clinical and biochemical studies on two cases of histidinemia. Pediatrics 32:216–227.

    Google Scholar 

  27. Woody, N. C., Snyder, C. H., andHarris, J. A. 1965. Histidinemia. Am. J. Dis. Child. 110:606–613.

    Google Scholar 

  28. Ladu, B. N. 1972. Histidinemia. Pages 338–350,in Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S. (eds.), The Metabolic Basis of Inherited Disease, McGraw-Hill, New York.

    Google Scholar 

  29. Woody, N. C. 1964. Hyperlysinemia. Am. J. Dis. Child. 108:543–553.

    Google Scholar 

  30. Ghadimi, H., Binnington, V. I., andPecora, P. 1965. Hyperlysinemia associated with retardation. N. Engl. J. Med. 273:723–729.

    Google Scholar 

  31. Armstrong, M. D., andRobinow, M. 1967. A case of hyperlysinemia: Biochemical and clinical observations. Pediatrics 39:546–554.

    Google Scholar 

  32. Gerritsen, T., andWaisman, H. A. 1972. Homocystinuria Pages 404–412,in Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S., (eds.), The Metabolic Basis of Inherited Disease, McGraw-Hill, New York.

    Google Scholar 

  33. Mudd, S. H., Finkelstein, J. D., Irreverre, F., andLaster, L., 1964. Homocystinuria; an enzymatic defect. Science 143:1443–1445.

    Google Scholar 

  34. Carson, N. A. J., andCarre, I. J. 1969. Treatment of homocystinuria with pyridoxine; a preliminary study. Arch. Dis Child. 44:387–392.

    Google Scholar 

  35. Folling, A. 1934. Über Ausscheidung von phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität. Hoppe-Seyler's Physiol. Chem. 227:169–176.

    Google Scholar 

  36. Knox, W. E. 1972. Phenylketonuria. Pages 266–295,in Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S. (eds.), The Metabolic Basis of Inherited Disease. McGraw-Hill, New York.

    Google Scholar 

  37. Koch, R., Blaskovics, M., Wenz, E., Fishler, K., andSchaeffler, G. 1974. Phenylalaninemia and phenylketonuria, pages 109–140,in Nyhan, W. L. (ed.), Heritable Disorders of Amino Acid Metabolism: Pattern of Clinical Expression and Genetic Variation, John Wiley, New York.

    Google Scholar 

  38. Scriver, C. R., andRosenberg, L. E. 1973. Phenylalanine. Pages 290–337,in Scriver, C. R., and Rosenberg, L. E. (eds.) Amino Acid Metabolism and Disorders, W. B. Saunders, Philadelphia.

    Google Scholar 

  39. Jervis, G. A. 1939. The genetics of phenylpyruvic oligophrenia. J. Ment. Sci. 85:719–725.

    Google Scholar 

  40. Jervis, G. A., Block, R. J., Bolling, D., andKanze, E. 1940. Phenylalanine content of blood and spinal fluid in phenylpyruvic oligophrenia. J. Biol. Chem. 134:105–113.

    Google Scholar 

  41. Jervis, G. A. 1947. Studies of phenylpyruvic oligophrenia: The position of the metabolic error. J. Biol. Chem. 169:651–656.

    Google Scholar 

  42. Jervis, G. A. 1953. Phenylpyruvic oligophrenia: Deficiency of phenylalanine-oxidizing system. Proc. Soc. Exp. Biol. Med. 82:514–515.

    Google Scholar 

  43. Mitoma, C., Auld, R. M., andUdenfriend, S.1957. On the nature of enzymic defect in phenylpyruvic oligophrenia. Proc. Soc. Exp. Biol. Med. 94:634–635.

    Google Scholar 

  44. Wallace, H. W., Moldave, K., andMeister, A.1957. Studies on conversion of phenylalanine to tyrosine in phenylpyruvic oligophrenia. Proc. Soc. Exp. Biol. Med. 94:632–633.

    Google Scholar 

  45. Kaufman, S. 1958. Phenylalanine hydroxylation cofactor in phenylketonuria. Science 128:1506–1508.

    Google Scholar 

  46. Friedman, P. A., Fisher, D. B., Kang, E. S., andKaufman, S. 1973. Detection of hepatic phenylalanine 4-hydroxylase in classical phenylketonuria. Proc. Natl. Acad. Sci. U.S.A. 70:552–556.

    Google Scholar 

  47. Kaufman, S. 1971. The phenylalanine hydroxylating system from mammalian liver. Adv. Enzymol. 35:245–319.

    Google Scholar 

  48. Barranger, J. A., Geiger, P. J., Huzino, A., andBessman, S. P. 1972. Isozymes of phenylalanine hydroxylase. Science 175:903–905.

    Google Scholar 

  49. Levy, H. L., Karolkewicz, V., Houghton, S. A., andMaccready, R. A. 1970. Screening the normal population in Massachusetts for phenylketonuria. N. Engl. J. Med. 282:1455–1458.

    Google Scholar 

  50. Linneweh, F., andEhrlich, M. 1960. Die renalen und prärenalen störugen des aminosäuren-stoffwechsels bei phenylalaninarmer ernährung. Klin. Wochenschr. 38:904–910.

    Google Scholar 

  51. Linneweh, F., andEhrlich, M. 1962. Zur pathogenese des schwachsinns bei phenylketonurie. Klin. Wochenschr. 40:225–226.

    Google Scholar 

  52. Pare, C. M., Sandler, M., andStacey, R. S. 1957. 5-Hydroxytryptamine deficiency in phenylketonuria. Lancet 1:551–553.

    Google Scholar 

  53. Boylen, J. B., andQuastel, J. H. 1962. Effects ofl-phenylalanine and sodium phenylpyruvate on the formation of melanin froml-tryosine in melanoma. Nature (London) 193:376–377.

    Google Scholar 

  54. Shah, S. N., Peterson, N. A., andMcKean, C. M. 1972. Lipid composition of human cerebral white matter and myelin in phenylketonuria. J. Neurochem. 19:2369–2376.

    Google Scholar 

  55. Lipton, M. A., Gordon, R., Guroff, G., andUdenfriend, S. 1967.p-Chlorophenylalanine-induced chemical manifestations of phenylketonuria in rats. Science 156:248–250.

    Google Scholar 

  56. Greengard, O., Yoss, M. S., andDelvalle, J. A. 1976. α-Methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in suckling rats. Science 192:1007–1008.

    Google Scholar 

  57. Gal, E. M., Roggeveen, A. E., andMillard, S. A. 1970.d, l[2-14C]p-Chlorophenylalanine as an inhibitor of tryptophan 5-hydroxylase. J. Neurochem. 17:1221–1235.

    Google Scholar 

  58. Weber, G. 1969. Inhibition of human brain pyruvate kinase and hexokinase by phenylalanine and phenylpyruvate: possible relevance to phenylketonuric brain damage. Proc. Natl. Acad. Sci. U.S.A. 63:1365–1369.

    Google Scholar 

  59. Shah, S. N., Peterson, N. A. andMcKean, C. M. 1969. Inhibition of sterol synthesis in vitro by metabolites of phenylalanine. Biochim. Biophys. Acta 187:236–242.

    Google Scholar 

  60. Silberberg, D. H. 1967. Phenylketonuria metabolites in cerebellum culture morphology. Arch. Neurol. 17:524–529.

    Google Scholar 

  61. Loo, Y. H., andRitman, P. 1964. New metabolites of phenylalanine. Nature (London) 203:1237–1239.

    Google Scholar 

  62. Loo, Y. H. 1967. Characterization of a new phenylalanine metabolite in phenylketonuria. J. Neurochem. 14:813–821.

    Google Scholar 

  63. Kurtz, D. J., Levy, H., andKanfer, J. N. 1972. Cerebral lipids and amino acids in the vitamin B6-deficient suckling rat. J. Nutr. 102:291–298.

    Google Scholar 

  64. Loo, Y. H., andMack, K. 1972. Effect of hyperphenylalaninemia on vitamin B6 metabolism in developing rat brain. J. Neurochem. 19:2377–2383.

    Google Scholar 

  65. Holtz, P., Credner, K., andHeppe, F. 1947. Über die beeinflussung der diurese durch oxytyramin und andere sympathicomimetische amine. Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 204:85–97.

    Google Scholar 

  66. Edwards, D. J., andBlau, K. 1973. Phenethylamines in brain and liver of rats with experimentally induced phenylketonuria-like characteristics. Biochem. J. 132:95–100.

    Google Scholar 

  67. McKean, C. M. 1972. The effects of high phenylalanine concentrations on serotonin and catecholamine metabolism in the human brain. Brain Res. 47:469–476.

    Google Scholar 

  68. McKean, C. M., Boggs, D. E. andPeterson, N. A. 1968. The influence of high phenylalanine and tryosine on the concentrations of essential amino acids in brain. J. Neurochem. 15:235–241.

    Google Scholar 

  69. Aoki, K. andSiegel, F. L. 1970. Hyperphenylalaninemia: Disaggregation of brain polyribosomes in young rats. Science 168:129–130.

    Google Scholar 

  70. Gal, E. M., Armstrong, J. C., andGinsberg, B. 1966. The nature of in vitro hydroxylation ofl-tryptophan by brain tissue. J. Neurochem. 13:643–654.

    Google Scholar 

  71. Loo, Y. H. 1974. Serotonin deficiency in experimental hyperphenylalaninemia. J. Neurochem. 23:139–147.

    Google Scholar 

  72. Weil-Malherbe, H. 1955. The concentration of adrenaline in human plasma and its relation to mental activity. J. Ment. Sci. 101:733–755.

    Google Scholar 

  73. Boylen, J. B., andQuastel, J. H. 1961. Effects ofl-phenylalanine and sodium phenylpyruvate on the formation of adrenaline froml-tyrosine in adrenal medulla in vitro. Biochem. J. 80:644–648.

    Google Scholar 

  74. Fellman, J. H., andDevlin, M. K. 1958. Concentration and hydroxylation of free phenylalanine in adrenal glands. Biochim. Biophys. Acta 28:328–332.

    Google Scholar 

  75. Cawte, J. E. 1957. Attempt to determine reaction to adrenaline in phenylketonuria. J. Ment. Defic. Res. 1:111–117.

    Google Scholar 

  76. Glazer, R. I., andWeber, G. 1971. The effects ofl-phenylalanine and phenylpyruvate on glycolysis in rat cerebral cortex. Brain Res. 33:439–450.

    Google Scholar 

  77. Miller, A. L., Hawkins, R. A., andVeech, R. L. 1973. Phenylketonuria: phenylalanine inhibits brain pyruvate kinase in vivo. Science 179:904–905.

    Google Scholar 

  78. Christensen, H. N. 1953. Metabolism of amino acids and proteins. Annu. Rev. Biochem. 22:233–260.

    Google Scholar 

  79. McKean, C. M., andPeterson, N. A. 1970. Glutamine in the phenylketonuric central nervous system. N. Engl. J. Med. 283:1364–1367.

    Google Scholar 

  80. Guroff, G., andUdenfriend, S. 1962. Studies on aromatic acid uptake by rat brain in vivo. J. Biol. Chem. 237:803–806.

    Google Scholar 

  81. Agrawal, H. C., Bone, A. H., andDavison, A. N. 1970. Effect of phenylalanine on protein synthesis in the developing rat brain. Biochem. J. 117:325–331.

    Google Scholar 

  82. Vahvelainen, M. L., andOja, S. S. 1975. Kinetic analysis of phenylalanine-induced inhibition in the saturable influx of tyrosine, tryptophan, leucine and histidine into brain cortex slices from adult and 7-day-old rats. J. Neurochem. 24:885–892.

    Google Scholar 

  83. Boggs, D. E., Deropp, R. S., andMcKean, C. M. 1964. The effects of high circulating phenylalanine on brain amino acids. Fed. Proc. 23:146.

    Google Scholar 

  84. O'Brien, D., andIbbot, F. Z. 1966. Effect of prolonged phenylalanine loading on the free amino-acid and lipid content of the infant monkey brain. Dev. Med. Child. Neurol. 8:724–728.

    Google Scholar 

  85. Richter, J. J., andWainer, A. 1971. Evidence for separate systems for the transport of neutral and basic amino acids across the blood-brain barrier. J. Neurochem. 18:613–620.

    Google Scholar 

  86. Alford, E. C., Stevenson, L. D., Vogel, F. S., andEngle, R. L. 1950. Neuropathological findings in phenyl-pyruvic oligophrenia (phenylketonuria). J. Neuropathol. Exp. Neurol. 9:298–310.

    Google Scholar 

  87. Prensky, A. L., Fishman, M. A., andDaftari, B. 1971. Differential effects of hyperphenylalaninemia on the development of the brain in the rat. Brain Res. 33:181–191.

    Google Scholar 

  88. Lindroos, O. F. C., andOja, S. S. 1971. Hyperphenylalaninemia and the exchange of tyrosine in adult rat brain. Exp. Brain Res. 14:48–60.

    Google Scholar 

  89. Swaiman, K. F., Hosfield, W. B. andLemieux, B. 1968. Elevated plasma phenylalanine concentration and lysine incorporation into ribosomal protein of developing brain. J. Neurochem. 15:687–690.

    Google Scholar 

  90. Antonas, K. N., andCoulson, W. F. 1975. Brain uptake and protein incorporation of amino acids studied in rats subjected to prolonged hyperphenylalaninemia. J. Neurochem. 25:309–314.

    Google Scholar 

  91. Peterson, N. A. andMcKean, C. M. 1969. The effects of individual amino acids on the incorporation of labelled amino acids into proteins by brain homogenates. J. Neurochem. 16:1211–1217.

    Google Scholar 

  92. Oja, S. S. 1972. Incorporation of phenylalanine, tryosine and tryptophan into protein of homogenates from developing rat brain: Kinetics of incorporation and reciprocal inhibition. J. Neurochem. 19:2057–2069.

    Google Scholar 

  93. Siegel, F. L., Aoki, K., andColwell, R. E. 1971. Polyribosome diaggregation and cell-free protein synthesis in preparations from cerebral cortex of hyperphenylalaninemic rats. J. Neurochem. 18:537–547.

    Google Scholar 

  94. Macinnes, J. W., andSchlesinger, K. 1971. Effects of excess phenylalanine on in vitro and in vivo RNA and protein synthesis and polyribosome levels in brains of mice. Brain Res. 29:101–110.

    Google Scholar 

  95. Roscoe, J. P., Eaton, M. D., andChoy, G. C. 1968. Inhibition of protein synthesis in Krebs 2 ascites cells and cell-free systems by phenylalanine and its effect on leucine and lysine in the amino acid pool. Biochem. J. 109:507–515.

    Google Scholar 

  96. Taub, F., andJohnson, T. C. 1975. The mechanism of polyribosome disaggregation in brain tissue by phenylalanine. Biochem. J. 151:173–180.

    Google Scholar 

  97. Copenhaver, J. H., Vacanti, J. P., andCarver, M. J. 1973. Experimental maternal hyperphenylalaninemia: Disaggregation of fetal brain ribosomes. J. Neurochem. 21:273–280.

    Google Scholar 

  98. Roberts, S., andMorelos, B. S. 1976. Role of ribonuclease action in phenylalanine-induced disaggregation of rat cerebral polyribosomes. J. Neurochem. 26:387–400.

    Google Scholar 

  99. Belitsina, N. V., andSpirin, A. S. 1970. Studies on the structure of ribosomes. IV. participation of aminoacyl-transfer RNA and peptidyl-transfer RNA in the association of ribosomal subparticles. J. Mol. Biol. 52:45–55.

    Google Scholar 

  100. Mathews, R. A., andWettstein, F. O. 1974. Differences in the subunit exchange between native and runoff single ribosomes. Biochim. Biophys. Acta 366:300–309.

    Google Scholar 

  101. Hughes, J. V., andJohnson, T. C. 1977. The effects of hyperphenylalaninemia on the concentrations of aminoacyl-transfer ribonucleic acid in vivo: A mechanism for the inhibition of neural protein synthesis by phenylalanine. Biochem. J. 162:527–537.

    Google Scholar 

  102. Hughes, J. V., andJohnson, T. C. 1978. Experimentally-induced and natural recovery from the effects of phenylalanine on brain protein synthesis. Biochim. Biophys. Acta 517:473–485.

    Google Scholar 

  103. Hughes, J. V., andJohnson, T. C. 1977. Hyperphenylalanemia: Effect on brain polyribosomes can be partially reversed by other amino acids. Science 195:402–404.

    Google Scholar 

  104. Dunlop, D. S., Van Elden, W., andLajtha, A. 1975. A Method for measuring brain protein synthesis rates in young and adult rats. J. Neurochem. 24:337–344.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biology, Kansas State University, 66506, Manhattan, Kansas

    Joseph V. Hughes & Terry C. Johnson

Authors
  1. Joseph V. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Terry C. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hughes, J.V., Johnson, T.C. Abnormal amino acid metabolism and brain protein synthesis during neural development. Neurochem Res 3, 381–399 (1978). https://doi.org/10.1007/BF00966321

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00966321

Keywords

Search

Navigation