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Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats

Published online by Cambridge University Press:  09 March 2007

Ana Triguero ,
Teresa Barber ,
Concha GarcÍa ,
Inmaculada R. Puertes ,
Juan Sastre  and
Juan R. ViÑa
Ana Triguero
Affiliation:
Departamento de Bioquímica y Biología MolecularUniversidad de Valencia, 46010-Valencia, Spain
Teresa Barber
Affiliation:
Departamento de Bioquímica y Biología MolecularUniversidad de Valencia, 46010-Valencia, Spain
Concha GarcÍa
Affiliation:
Departamento de Bioquímica y Biología MolecularUniversidad de Valencia, 46010-Valencia, Spain
Inmaculada R. Puertes
Affiliation:
Departamento de Bioquímica y Biología MolecularUniversidad de Valencia, 46010-Valencia, Spain
Juan Sastre
Affiliation:
Departamento de Fisiología, Facultades de Farmacia y Medicina, Universidad de Valencia, 46010-Valencia, Spain
Juan R. ViÑa
Affiliation:
Departamento de Bioquímica y Biología MolecularUniversidad de Valencia, 46010-Valencia, Spain
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Abstract

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To study the fate of l-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, l-cystathionine levels were significantly higher, l-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, l-ornithine, l-citrulline and l-arginine and blood urea were significantly greater. Urea excretion was also higher in PPG-treated rats when compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of γ-cystathionase was reflected in the blood levels of amino acids, because the L-methionine: l-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater. Histological examination of liver and kidney showed no changes in PPG-treated rats when compared with controls. The administration of N-acetylcysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver l-cysteine production was impaired by the blockage of the trans-sulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that may spare l-cysteine.

Keywords

LiverCysteinePropargylglycineCystathionase
Type
General Nutrition
Information
British Journal of Nutrition , Volume 78 , Issue 5 , November 1997 , pp. 823 - 831
Copyright
Copyright © The Nutrition Society 1997

References

REFERENCES

Barber, T., Viña, J. R., Viña, J. & Cabo, J. (1985) Decreased urea synthesis in cafeteria-induced obesity in the rat. Biochemical Journal 230, 675–691.CrossRefGoogle Scholar
Beutler, E. (1989) Nutritional and metabolic aspects of glutathione. Annual Review of Nutrition 9, 287–302.CrossRefGoogle ScholarPubMed
Beliveau-Carey, G., Cheung, C. W., Cohen, N. S., Brusilow, S. & Raijman, L. (1993) Regulation of urea and citrulline synthesis under physiological conditions. Biochemical Journal 292, 241–247.CrossRefGoogle ScholarPubMed
Brigelius, R., Muckel, C., Akerboom, T. P. M. & Sies, H. (1983) Identification and quantitation of glutathione in hepatic protein mixed disulfides and its relationship to disulfide. Biochemical Pharmacology 32, 2529–2534.CrossRefGoogle ScholarPubMed
Burnett, G., Marcotte, P. & Walsh, C. (1980). Mechanism-based inactivation of pig heart l-alanine transaminase by l-propargylglycine. Journal of Biological Chemistry 255, 3487–3491.Google Scholar
Cornell, N. W., Zuurendonk, P. F., Kerich, M. J. & Straight, C. B. (1984) Selective inhibition of alanine aminotransferase and aspartate aminotransferase in rat hepatocytes. Biochemical Journal 220, 707–716.Google Scholar
Crespo, M. L., Giménez, A., Bas, T., García, C., Puertes, I. R. & Viña, J. R. (1997) Effect of nitrous oxide and propofol on amino acid metabolism in neoplasic patients. Nutrition and Cancer 27, 80–83.Google Scholar
Finkelstein, J. D. (1990) Methionine metabolism in mammals. Journal of Nutritional Biochemistry 1, 228–237.CrossRefGoogle ScholarPubMed
Gaitonde, M. K. (1967) A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids. Biochemical Journal 104, 627–633.Google Scholar
Griffith, O. W. (1987) Mammalian sulfur amino acid metabolism: an overview. In Methods in Enzymology, Vol. 143, pp. 336–376 [Jakoby, W.B. and Griffith, O. W., editors]. New York: Academic Press Inc.Google Scholar
Heinonen, K. (1973) Studies on cystathionase activity in rat liver and brain during development.Effects of hormones and amino acids in vivo. Biochemical Journal 136, 1011–1015.CrossRefGoogle ScholarPubMed
Laidlaw, S. A. & Kopple, J. D. (1987) Newer concepts of the indispensable amino acids. American Journal of Clinical Nutrition 46, 593–605.CrossRefGoogle ScholarPubMed
Lu, S. C., Kuhlenkamp, J., García-Ruiz, C. & Kaplowitz, N. (1991) Hormone-mediated down-regulation of hepatic glutathione synthesis in the rat. Journal of Clinical Investigation 88, 260–269.Google Scholar
Nunn, J. F. (1987) Clinical aspects of the interactions between nitrous oxide and vitamin B12. British Journal of Anaesthesiology 59, 3–13.CrossRefGoogle ScholarPubMed
Nuzum, C. & Snodgrass, P. (1976) Multiple assays of the five urea-cycle enzymes in human liver homogenates. In Urea Cycle, pp. 325–355 [Grisolía, S., Báguena, R. and Mayor, F., editors]. New York: John Wiley and Sons.Google Scholar
Pallardó, F. V., Sastre, J., Asensi, M., Rodrigo, F., Estrela, J. M. & Viña, J. (1991) Physiological changes in glutathione metabolism in foetal and newborn rat liver. Biochemical Journal 274, 891–893.Google Scholar
Rao, A. M., Drake, M. R. & Stipanuk, M. H. (1990) Role of the trans-sulfuration pathway and of γ-cystathionase activity in the formation of cysteine and sulfate from L-methionine in rat hepatocytes. Journal of Nutrition 120, 837–845.CrossRefGoogle Scholar
Reed, D. J. (1995) Cystathionine. In Methods in Enzymology, Vol. 252, pp. 92–102. [Packer, L., editor]. New York: Academic Press.Google Scholar
Rémésy, C., Demigné, C. & Aufrere, J. (1978) Inter-organ relationships between glucose, lactate and amino acids in rats fed on high carbohydrate or high-protein diets. Biochemical Journal 170, 321–329.Google Scholar
Rose, W. C. & Wixom, R. L. (1955) The amino acid requirement of man. The sparing effect of cystine on the methionine requirement. Journal of Biological Chemistry 216, 763–773.Google Scholar
Sturman, J. A., Gaull, G. & Raiha, N. C. R. (1970) Absence of cystathionase in human fetal liver: is cystine essential? Science 169, 74–75.Google Scholar
Tateishi, N., Higashi, T., Shinya, S., Naruse, A. & Sakamoto, Y. (1974) Studies on the regulation of glutathione level in rat liver. Journal of Biochemistry, Tokyo 75, 93–103.CrossRefGoogle ScholarPubMed
Viña, J., Giménez, A., Puertes, I. R., Gascó, E. & Viña, J. R. (1992) Impairment of cysteine synthesis from methionine in rats exposed to surgical stress. British Journal of Nutrition 68, 421–429.CrossRefGoogle ScholarPubMed
Viña, J., Sáez, G. T., Wiggins, D., Roberts, A. F. C., Hems, R. & Krebs, H. A. (1983) The effect of cysteine oxidation on isolated hepatocytes. Biochemical Journal 212, 39–44.CrossRefGoogle ScholarPubMed
Viña, J., Vento, M., García-Sala, F., Puertes, I. R., Gascó, E., Sastre, J., Asensi, M. & Pallardó, F. V. (1995) l-Cysteine and glutathione metabolism are impaired in premature infants due to cystathionase deficiency. American Journal of Clinical Nutrition 61, 1067–1069.Google Scholar
Wallenstein, S., Zucker, C. L. & Fleiss, J. L. (1980) Some statistical methods useful in circulation research. Circulation Research 47, 1–9.Google Scholar
Washtien, W. & Abeles, R. (1977) Mechanism of inactivation of γ-cystathionase by the acetylenic substrate analogue propargylglycine. Biochemistry 16, 2485–2491.CrossRefGoogle ScholarPubMed