Skip to main content
SpringerLink
Log in

Zur Biosynthese von Aminosäuren aus Glukose im Zentralnervensystem beim Parkinsonsyndrom

Biosynthesis of amino acids in human central nervous system and Parkinsonism

  • Published:
Archiv für Psychiatrie und Nervenkrankheiten Aims and scope Submit manuscript

Summary

The incorporation of labelled carbon from glucose U-14C into CSF amino acids was investigated in three patients with Parkinson's disease and in three control persons with comparable age and physical stature.

  1. 1.

    Comparing the specific radioactivities of serum and CSF one can postulate that the labelled amino acids found in the CSF are synthesized mainly by brain tissue.

  2. 2.

    The resorption of glucose into the CNS and therefore the synthesis of amino acids from glucose was more rapid in controls; labelled alanine and glutamine appeared later in the CSF of the patients.

  3. 3.

    As expected, in the controls the specific radioactivity of glutamic acid was found to be higher than that of glutamine, in patients the labelling of glutamine was higher as was that of serine, glycine, aspartic acid and asparagine.

From our knowledge concerning the compartmentation of the metabolism of glutamate, we assume that in Parkinsonism the metabolic activity of neurons is reduced but that of astroglia is enhanced.

Zusammenfassung

Bei drei Parkinsonpatienten wurde im Vergleich zu drei dem Alter und Status entsprechenden Personen der Einbau von markiertem Kohlenstoff aus U-14C-Glukose in Linquoraminosäuren untersucht. Die Ergebnisse lassen sich folgendermaßen zusammenfassen:

  1. 1.

    Der Vergleich der spezifischen Aktivitäten der Aminosäuren in Blut und Liquor zeigte, daß vorwiegend das Hirngewebe als Ursprung der markierten Arminosäuren im Liquor anzusehen ist.

  2. 2.

    Die Resorption der Glukose in das Zentralnervensystem und damit der Umsatz der Glukose zu Aminosäuren war bei den Kontrollpersonen rascher als bei den Patienten, was u.a. aus dem Zeitpunkt des Auftauchens von markiertem Alanin und Glutamin im Lumballiquor geschlossen werden kann.

  3. 3.

    Während bei den Kontrollpersonen die spezifische Aktivität der Glutaminsäure im Liquor höher war als die Markierung des Glutamins, war bei den Parkinsonpatienten die Markierung des Glutamins höher, desgleichen die Markierung von Serin und Glycin, aber auch von Asparaginsäure und Asparagin.

Auf Grund der bekannten Kompartimentierung des Glutamatstoffwechsels im ZNS zeigt dieses Ergebnis, daß bei der Paralysis agitans nicht nur —wie man bisher annahm —ein neuraler Effekt vorliegt, sondern auch gliäre Elemente an der Störung beteiligt sind. Einer verminderten metabolischen Aktivität neuronalen Gewebes steht eine gesteigerte der Astroglia gegenüber.

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

Similar content being viewed by others

Literatur

  • Baker N, Shreeve WW, Shioley RA, Incefy GE, Miller M (1954) C-14-Studies in carbohydrate metabolism I. The oxydation of glucose in normal human subjects. J Biol Chem 211:575–592

    Google Scholar 

  • Baxter CF (1976) Intrinsic amino acid levels and the blood-brain barrier. In: Lajtha A, Ford DH (eds) Progress in Brain Research, Elsevier, Amsterdam 29: 429–444

  • Van den Berg CJ, Garfinkel D (1971) A stimulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem J 123:211–218

    Google Scholar 

  • Van den Berg CJ, Mela P, Waelsh H (1966) On the contribution of the tricarboxylic acid cycle to the synthesis of glutamate, glutamine and aspartate in brain. Biochem Biophys Res Comm 23:479–484

    Google Scholar 

  • Berl S, Clarke DD (1969) Compartmentation of amino acid metabolism. In: Lajtha A (ed) Handbook of Neurochemistry, vol 2. Plenum Press, New York, pp 465–469

    Google Scholar 

  • Bhattacharya AN, Marks BH (1969) Reserpine and chlorpromazine-induced changes in hypothalamo-hypophysal-adrenal system in rats in the persence and absence of hypothermia J Pharmacol Exp Ther 165:108–116

    Google Scholar 

  • Birkmeyer W, Riederer P (1980) Die Parkinsonkrankheit, Biochemie, Klinik, Therapie. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Brennemann R, Kaufman S (1964) The role of tetrahydropteridines in the enzymatic conversion of tyrosine to 3,4-dihydroxyphenylalanine. Biochem Biophys Res Commm 17:177–183

    Google Scholar 

  • Bruck H, Gerstenbrand F, Gründig E, Teuflmayr R (1964) Über Ergebnisse von Liquoranalysen beim Parkinsonsyndrom Acta Neuropathol 3:638–644

    Google Scholar 

  • Cremer JE (1964) Amino acid metabolism in rat brain studied with 14-C-labelled glucose. J Neurochem 11:165–185

    Google Scholar 

  • Ellenbogen L, Taylor RJ jr, Brundage GB (1965) On the role of pteridines as cofactors for tyrosine hydroxylase. Biochem Biophys Res Comm 19:708–715

    Google Scholar 

  • Gaitonde MK, Dahl DR, and Elliott KAC (1963) Entry of glucose carbon into amino acids of rat brain and liver in vivo after injection of uniformly 14-C-labelled glucose. Biochem J 94:345–352

    Google Scholar 

  • Gaitonde MK, Nixey RWK (1972) Sources of error in the determination of specific radioactivity of amino acids isolated by ion-exchange-chromatography. Anal Biochem 50:417–429

    Google Scholar 

  • Garfinkel D (1970) Simulation study of brain compartiments. I. Fuel sources and GABA metabolism. Brain Res 23:387–408

    Google Scholar 

  • Van Gelder NM, Drujan BD (1980) Alteration in the compartmentalyzed metabolism of glutamic acid with changed cerebral conditions Brain Res 200:443–445

    Google Scholar 

  • Giorgnieff MF, Kemel ML, Glowinski J (1977) Presynaptic effect of L-glutamic acid on the release of dopamine in rat striatal slices. Neurose Letters 6:73–77

    Google Scholar 

  • Gjessing LR, Gjesdahl P, Dietrichsen P, Presthus J (1974) Free amino acids in the cerebrospinal fluid in old age and in Parkinson's disease. Europ Neurol 12:33–37

    Google Scholar 

  • Gordon RD, Hunt A, Patel AJ (1981) The cellular distribution of certain enzymes associated with the metabolic compartmentation of glutamate. Biochem Soc Trans 9:115–116

    Google Scholar 

  • Gründig E, Ernsthausen U, Mayer W (1983) The influence of amino acids on the activity of the tyrosine hydroxylase in rat brain preparations. Eingereicht bei Experientia

  • Gründig E, Gerstenbrand F (1970) Über den Zusammenhang zwischen der Parkinsonsymptomatik und einer Störung des Aminosäurehaushaltes im ZNS. Klin Wochenschr 83:811–816

    Google Scholar 

  • Gründig E, Hanbauer I (1970) Gehirn —Aminosäuren beim Phenothiazin-Parkinsonoid. Das medikamentöse Parkinsonoid bei der Ratte als Modell für biochemische Untersuchungen des Parkinsonsyndroms. J Neurochem 17:215–220

    Google Scholar 

  • Gründig E, Abdel Raheem K, Salvenmoser F, Schedl R, Weiß J (1976) Drug induced Parkinsonism in the rat-a model for biochemical investigation of the Parkinson-Syndrome. The incorporation of D-glucose-14-C(U) in amino acids of brain and liver from rats, pretreated with reserpine or with phenothiazines. Psychopharmacology 47:111–118

    Google Scholar 

  • Gründig E, Salvenmoser F, Bretschneider R (1963) Über den Einfluß der Glutaminsäure auf den Stoffwechsel, speziell des Zentralnervensystems. Z Ges Exp Med 137:94–107

    Google Scholar 

  • Hamberger A, Jakobson I, Lindroth P, Mopper K, Nyström B, Sandberg M, Molin SO, Svenberg U (1981) Neuron-glia interactions in the biosynthesis and release of transmitter amino acids. Adv Biochem Psychopharmacol 29:509–518

    Google Scholar 

  • Hare TA, Beasly BL, Chambers RA, Boehme DH, Vogel WH (1973) Dopa and amino acid levels in plasma and cerebrospinal fluid of patients with Parkinson's disease before and during treatment with L-Dopa. Clin Chim Acta 45:273–280

    Google Scholar 

  • Hills AG, Reid EL, Kerr WD (1972) Circulatory transport of L-Glutamine in fasted mammals, cellular Sources of urine ammonia. Am J Physiol 223:1470–1476

    Google Scholar 

  • Lakke JWF, Teelken AW (1976) Amino acid abnormalities in cerebrospinal fluid of patients with parkinsonism and extrapyramidal disorders. Neurology 26:489–493

    Google Scholar 

  • Lindsay TR, Bachelard HS (1966) Incorporation of 14-C- from glucose into α-keto acids and amino acids in rat brain and liver in vivo. Biochem Pharmacol 15:1045–1052

    Google Scholar 

  • Minchin MCW (1977) The release of amino acids synthesised from various compartmented percursors in rat spinal cord slices. Exp Brain Res 29:515–526

    Google Scholar 

  • Moore S, Stein WH (1948) Photometric ninhydrin for use in the chromatography of amino acids. J Biol Chem 176:367–388

    Google Scholar 

  • Oldendorf WH (1971) Brain uptake of radiolabelled amino acids, amines, and hexoses after arterial injection. Am J Physiol 221:1629–1639

    Google Scholar 

  • Pantlitschko M, Gründig E (1958) Über die Aminosäurezusammensetzung von trypsinresistenten Phosphopeptonen aus α-Casein. Monatsh Chem 89:274–284

    Google Scholar 

  • Patel MS (1974) The relative significance of CO2-fixing enzymes in the metabolism of rat brain. J Neurochem 22:717–724

    Google Scholar 

  • Raheem Abdel K, Gründig E, Salvenmoser F, Schedl R, Weiß J (1979) Incorporation of U-14-C-glucose into metabolites of brain, liver and blood of rats, pretreated with reserpine or phenothiazines. J Clin Chem Clin Biochem 17:341–348

    Google Scholar 

  • Rinne UK, Laaksonen H, Riekkinen P, Sonninen v (1974) Brain glutamic acid decarboxylase activity in Parkinson's disease. Eur Neurol 12:13–19

    Google Scholar 

  • Rose SPR (1967) Amino acid metabolism in isolated neuronal and glial cells. Biochem J 102: 21P

  • Rose SPR (1968) Glucose and amino acid metabolism in isolated neuronal and glial cell fractions in vitro. J Neurochem 15:1415–1429

    Google Scholar 

  • Sacks W (1957) Cerebral metabolism of isotopic glucose in normal human subjects. J Appl Physiol 10:37–44

    Google Scholar 

  • Sacks W (1965) Cerebral metabolism of doubly labelled glucose in humans in vivo. J Appl Physiol 20:117–130

    Google Scholar 

  • Van Sande M, Caers J, Lovental A (1971) Cerebrospinal fluid amino acids in extrapyramindal disorders before and after L-Dopa treatment. Z Neurol 199:24–29

    Google Scholar 

  • Selbach H (1963) Über regulationsdynamische Wirkungsgrundlagen der Psychopharmaka in anthropoligisischen und naturwissenschaftlichen Grundlagen der Pharmako-Psychiatrie. Thieme, Stuttgart

    Google Scholar 

  • Shank RP, Aprison MH (1981) Present status and significance of the glutamic cycle in neuronal tissue. Life Sci 28:837–842

    Google Scholar 

  • Shank RPS, Aprison MH, Baxter CF (1973) Precursors of glycine in the nervous system: comparison of the specific activities in glycine and other amino acids after administration of U-14-C-serine or 1,5-14-C-citrate to the rat. Brain Res 52:301–308

    Google Scholar 

  • Shimada M, Kibara T, Kuritomo K, Watanabe M (1973) Incorporation of 14-C- from (U-14-C-D-) glucose into free amino acids in mouse brain loci in vivo under normal conditions. J Neurochem 20:1337–1344

    Google Scholar 

  • Tursky T, Lassanova M (1977) On the localisation of the two glutaminate pools in the brian. Comparison of their metabolic activities in human and rat brain tissue in vitro. Physiol Bohemoslovaca 26:201–208

    Google Scholar 

  • Tursky CT, Rusak M, Lassanova M, Ruscakova D (1979) 14C-amino acid formation from labelled glucose and/or acetate in brain cortex slices with experimentally elicited proliferation of astroglia. Correlation of biochemical and morphological changes. J Neurochem 33:1203–1215

    Google Scholar 

  • Whittaker VP (1968) The subcellular distribution of amino acids in brain and its relation to a possible transmitter function for these compounds. In: Structure and functions of inhibitory neuronal mechanisms. Pergamon Press, Oxford New York 1968. Proceedings of the 4th Int. Meeting of Neurobiologists, Stockholm, pp 487–504

    Google Scholar 

  • Wiechert P (1963) Über die Permeabilität der Blut-Liquor-Schranke für einige Aminosäuren. Acta Biol Med Germ 10:305–310

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinisch Chemisches Institut der Universität Wien, Währingerstrasse 10, A-1090, Wien

    E. Gründig & F. Gerstenbrand

  2. Neurologie in der Universitätsklinik, Innsbruck, Austria

    W. Mayer

Authors
  1. E. Gründig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Gerstenbrand
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Sonderdruckanfragen an: E. Gründig

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gründig, E., Mayer, W. & Gerstenbrand, F. Zur Biosynthese von Aminosäuren aus Glukose im Zentralnervensystem beim Parkinsonsyndrom. Arch Psychiatr Nervenkr 233, 397–408 (1983). https://doi.org/10.1007/BF00346090

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00346090

Key words

Schlüsselwörter

Search

Navigation