Skip to main content
Log in

Aromatic and branched-chain amino acids in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy

  • Original Contributions
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Concentrations of the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine and the aromatic amino acids (AAAs) phenylalanine and tyrosine were measured in three areas of dissected brain tissue obtained at autopsy from nine cirrhotic patients who died in hepatic encephalopathy. The controls were an equal number of subjects free from neurological, psychiatric or hepatic diseases, matched for age and time interval from death to freezing of autopsied brain samples. Amino acids were measured using high-performance liquid chromatography with fluorimetric detection. In brain tissue of cirrhotic patients, no changes in BCAA concentrations were observed compared with controls. On the other hand, phenylalanine levels were found to be increased 141% in prefrontal cortex, 86% in frontal cortex and 26% in caudate nucleus, and tyrosine content was increased by 71% in prefrontal cortex and 28% in frontal cortex with no significant increase in caudate nucleus. Alterations in the concentration of AAAs may lead to disturbances of monoamine neurotransmitters in brain. Such changes could play a role in the pathogenesis of hepatic encephalopathy resulting from chronic liver disease in man.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Battistin, L., and Zanchin, G. (1980). The role of amino acids in hepatic encephalopathy. In Neurochemistry and Clinical Neurology, Alan R. Liss, New York, pp. 315–326.

    Google Scholar 

  • Butterworth, R. F., Giguère, J. F., Lavoie, J., and Pomier Layrargues, G. (1987). Ammonia: Key factor in the pathogenesis of hepatic encephalopathy.Neurochem. Pathol. 6: 1–12.

    Google Scholar 

  • Cascino, A., Cangiano, C., Fiaccadori, F., Ghinelli, F., Merli, M., Pelosi, G., Riggio, O., Rossi Fanelli, F., Sacchini, D., Stortoni, M., and Capocaccia, L. (1982). Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy.Digest. Dis. Sci. 27: 828–832.

    Google Scholar 

  • Guilleret, G., Pomier Layrargues, G., Pons, F., Cadilhac, J., and Michel, H. (1980). Changes in brain catecholamine levels in human cirrhotic hepatic encephalopathy.Gut 21: 565–569.

    Google Scholar 

  • Curzon, G., Kantamaneni, B. D., Fernando, J. C., Woods, M. S., and Cavanagh, J. B. (1975). Effects of chronic porto-caval anastomosis on brain tryptophan, tyrosine and 5-hydroxytryptamine.J. Neurochem. 24: 1065–1070.

    Google Scholar 

  • DeArmond, S. J., Fusco, M. M., and Dewey, M. M. (1976).Structure of the Human Brain: A Photographic Atlas, 2nd ed., Oxford University Press, New York.

    Google Scholar 

  • Fischer, J. E., and Baldessarini, R. J. (1971). False neurotransmitters and hepatic failure.Lancet 2: 75–80.

    Google Scholar 

  • Fischer, J. E., and Baldessarini, R. J. (1976). Pathogenesis and therapy of hepatic coma. In Popper H., and Shaffner F. (eds.),Progress in Liver Diseases, Grune and Stratton, New York, pp. 363–397.

    Google Scholar 

  • Fischer, J. E., Yoshimura, N., Aguirre, A., James, J. H., Cummings, M. G., Abel, R. M., and Deindoerfer, F. (1974). Plasma amino acids in patients with hepatic encephalopathy. Effects of amino acid infusions.Am. J. Surg. 127: 40–47.

    Google Scholar 

  • Fischer, J. E., Rosen, H. M., Ebeid, A. M., James, J. H., Keane, J. M., and Soeters, P. B. (1976). The effect of normalization of plasma amino acids on hepatic encephalopathy in man.Surgery 80: 77–91.

    Google Scholar 

  • Gaillard, J. M. (1985). Neurochemical regulation of the states of alertness.Ann. Clin. Res. 17: 175–184.

    Google Scholar 

  • Hamberger, A. and Nystrom, B. (1984). Extra- and intracellular amino acids in the hippocampus during development of hepatic encephalopathy.Neurochem. Res. 9: 1181–1192.

    Google Scholar 

  • Berlin, P. M., James, J. H., Nachbauer, C. A., and Fischer, J. E. (1983). Effect of total hepatectomy and administration of branched-chain amino acids on regional norepinephrine, dopamine and amino acids in rat brain.Ann. Surg. 198: 172–177.

    Google Scholar 

  • James, J. H., Escourrou, J., and Fischer, J. E. (1978). Blood-brain neutral amino acid transport activity is increased after portocaval anastomosis.Science 200: 1395–1397.

    Google Scholar 

  • Jeppsson, B., James, J. H., Edwards, L. L., and Fischer, J. E. (1985). Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats.Eur. J. Clin. Invest. 15: 179–187.

    Google Scholar 

  • Jonung, T., Ramzy, A., Herlin, P., James, H. H., Edwards, L., and Fisher, J. E. (1985). Indole amines and amino acids in various brain regions after infusion of branched chain amino acids into hepatectomized rats.Eur. Surg. Res. 17: 83–90.

    Google Scholar 

  • Kamata, S., Okada, A., Watanabe, T., Kawashima, Y., and Wada, H. (1980). Effects of dietary amino acids on brain amino acids and transmitter amines in rats with a portacaval shunt.J. Neurochem. 35: 1190–1199.

    Google Scholar 

  • Kurtz, D., Zenglein, J. P., Imler, M., Girardel, M., Grinspan, G. Peter, B., and Rohmer, F. (1972). Etude du sommeil nocture au cours de l'encéphalopathie porto-cave.Electroenceph. Clin. Neurophysiol. 33: 167–178.

    Google Scholar 

  • Lavoie, J., Giguère, J. F., Pomier Layrargues, G., and Butterworth, R. F. (1987). Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy.J. Neurochem. 49: 692–697.

    Google Scholar 

  • Mans, A. M., and Hawkins, R. A. (1986). Brain monoamines after portacaval anastomosis.Metab. Brain Dis. 1: 45–52.

    Google Scholar 

  • Mans, A. M., Saunders, S. J., Kirsh, R. E., and Biebuyck, J. F. (1979). Correlation of plasma and brain amino acid and putative neurotransmitter alterations during acute hepatic coma in the rat.J. Neurochem. 32: 285–292.

    Google Scholar 

  • Mans, A. M., Biebuyck, J. F., Davis, D. W., and Hawkins, R. A. (1984). Portacaval anastomosis: Brain and plasma amino acid metabolite abnormalities and the effect of nutritional therapy.J. Neurochem. 43: 697–705.

    Google Scholar 

  • Mans, A. M., Consevage, M. W., DeJoseph, M. R., and Hawkins, R. A. (1987). Regional brain monoamines and their metabolites after portacaval shunting.Metab. Brain Dis. 2: 183–193.

    Google Scholar 

  • Mattson, W. J., Iob, V., Sloan, M., Coon, W. W., Turcotte, S. G., and Child, C. G. (1970). Alterations of individual free amino acids in brain during acute hepatic coma.Surg. Gynecol. Obstet. 130: 263–266.

    Google Scholar 

  • Munro, H. N., Fernstrom, J. D., and Wurtman, R. J. (1975). Insulin, plasma amino acid imbalance, and hepatic coma.Lancet 1: 722–724.

    Google Scholar 

  • Perry, T. L., Berry, K., Hansen, S., Diamond, S., and Mok, C. (1971a). Regional distribution of amino acids in human brain obtained at autopsy.J. Neurochem. 18: 513–519.

    Google Scholar 

  • Perry, T. L., Hansen, S., Berry, K., Mok, C., and Lesk, D. (1971b). Free amino acids and related compounds in biopsies of human brain.J. Neurochem. 18: 521–528.

    Google Scholar 

  • Plum, F., and Hindfelt, B. (1976). The neurological complications of liver disease. In Vinken, P. J., and Bruyn, G. W. (eds.),Metabolic and Deficiency Diseases of the Nervous System, Handbook of Clinical Neurology, Vol. 27, American Elsevier, New York, pp. 349–377.

    Google Scholar 

  • Record, C. O., Buxton, B., Chase, R. A., Curzon, G., Murray-Lyon, I. M., and Williams, R. (1976). Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy.Eur. J. Clin. Invest. 6: 387–394.

    Google Scholar 

  • Rosen, M. H., Yoshimura, N., Hodgman, J. M., and Fischer, J. E. (1977). Plasma amino acid patterns in hepatic encephalopathy of differing etiology.Gastroenterol 72: 483–487.

    Google Scholar 

  • Shiota, T., Nakatsukasa, H., Fujiwara, M., Takei, N., Yamauchi, Y., Kobayashi, M., Watanabe, A., and Nagashima, H. (1984). Plasma amino acid imbalance in alcoholic liver cirrhosis.Biochem. Med. 32: 181–188.

    Google Scholar 

  • Smith, A. R., Rossi-Fanelli, F., Ziparo, V., James, J. H., Perelle, B. A., and Fischer, J. E. (1978). Alterations in plasma and CSF amino acids, amines and metabolites in hepatic coma.Ann. Surg. 187: 343–350.

    Google Scholar 

  • Zanchin, G., Rigotti, P., Dussini, N., Vassanelli, P., and Battistin, L. (1979). Cerebral amino acid levels. and uptake in rats after portocaval anastomosis. II. Regional studies in vivo.J. Neurosci. Res. 4: 301–310.

    Google Scholar 

  • Zieve, L. (1982). Hepatic encephalopathy. In Schiff, L., and Schiff, E. R. (eds.),Diseases of the Liver, Lippincott, Philadelphia, pp. 433–459.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bergeron, M., Layrargues, G.P. & Butterworth, R.F. Aromatic and branched-chain amino acids in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Metab Brain Dis 4, 169–176 (1989). https://doi.org/10.1007/BF01000293

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01000293

Key words

Navigation