Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-28T18:19:12.333Z Has data issue: false hasContentIssue false
  • English
  • Français

Interactions between propionate and amino acid metabolism in isolated sheep hepatocytes

Published online by Cambridge University Press:  09 March 2007

C. Demigné ,
C. Yacoub ,
C. Morand  and
C. RéMésy
C. Demigné
Affiliation:
INRA Laboratoire des Maladies Metaboliques, Centre de Recherches, Theix-F-63122, Ceyrat, France
C. Yacoub
Affiliation:
INRA Laboratoire des Maladies Metaboliques, Centre de Recherches, Theix-F-63122, Ceyrat, France
C. Morand
Affiliation:
INRA Laboratoire des Maladies Metaboliques, Centre de Recherches, Theix-F-63122, Ceyrat, France
C. RéMésy
Affiliation:
INRA Laboratoire des Maladies Metaboliques, Centre de Recherches, Theix-F-63122, Ceyrat, France
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The purpose of the present study was to evaluate the contribution of various substrates to glucose synthesis in isolated sheep hepatocytes, and more specifically to quantify the contribution of propionate to gluconeogenesis. Liver cells from fed sheep have a very high capacity for propionate utilization and conversion into glucose. The glucogenicity of lactate or amino acids was very low in hepatocytes from fed sheep, but was significantly increased in hepatocytes from starved animals. Amino acids such as alanine or glutamine were characterized by a substantial utilization towards ureogenesis, whereas their conversion to glucose was very low. Propionate utilization and conversion into glucose was inhibited by butyrate, ammonia and especially ethanol (by up to 80%). Ethanol promoted a striking accumulation of intracellular malate in hepatocytes incubated with propionate (reaching 14.9 μmol/g cell) and led to a depletion of phosphoenolpyruvate; ethanol inhibition could be counteracted by pyruvate. Propionate and butyrate enhanced ureogenesis from ammonia in ruminant liver cells but their effects were not additive. Propionate also elicited a marked increase in cellular concentrations of phosphoserine and serine, particularly in the presence of ammonia; such effects could influence phospholipid metabolism in the liver. These findings emphasize the contribution of propionate, compared with the other glucogenic substrates, to glucose synthesis in ruminants and point to the possibilities of modulation of the glucogenicity of propionate by various substrates which may be present in portal blood.

Keywords

GluconeogenesisHepatocytesPropionateAmino acidsSheep
Type
Metabolic Effects of Dietary Constituents
Information
British Journal of Nutrition , Volume 65 , Issue 2 , March 1991 , pp. 301 - 317
Copyright
Copyright © The Nutrition Society 1991

References

REFERENCES

Aiello, R. J. & Armentano, L. E. (1987). Effects of volatile fatty acids on propionate metabolism and gluconeogenesis in caprine hepatocytes. Journal of Dairy Science 70, 2504–2510.CrossRefGoogle ScholarPubMed
Aiello, R. J., Armentano, L. E., Bertics, S. J. & Murphy, A. T. (1989). Volatile fatty acid uptake and propionate metabolism in ruminant hepatocytes. Journal of Dairy Science 72, 942–949.CrossRefGoogle ScholarPubMed
Baird, G. D., Lomax, M. A., Symonds, H. W. & Shaw, S. R. (1980). Net hepatic and splanchnic metabolism of lactate, pyruvate and propionate in dairy cows in vivo in relation to lactation and nutrient supply. Biochemical Journal 186, 47–57.CrossRefGoogle ScholarPubMed
Baird, G. D. & Young, J. L. (1975). The response of the key gluconeogenic enzymes in bovine liver to various dietary and hormonal regimes. Journal of Agricultural Science, Cambridge 84, 227–230.CrossRefGoogle Scholar
Ballard, F. J., Hanson, R. W. & Kronfeld, D. S. (1969). Gluconeogenesis and lipogenesis in tissues from ruminant and non-ruminant animals. Federation Proceedings 28, 218–231.Google Scholar
Bergman, E. N., Roe, E. R. & Kon, K. (1966). Quantitative aspects of propionate metabolism and gluconeogenesis in sheep. American Journal of Physiology 211, 793–799.CrossRefGoogle ScholarPubMed
Brosnan, J. T. & Williamson, D. H. (1974). Mechanism of the formation of alanine and aspartate in rat liver in vivo after administration of ammonium chloride. Biochemical Journal 138, 459–462.CrossRefGoogle ScholarPubMed
Bush, R. S. & Milligan, L. P. (1971). Study of the mechanism of inhibition of ketogenesis by propionate in bovine liver. Canadian Journal of Animal Science 51, 121–127.CrossRefGoogle Scholar
Cathelineau, L., Petit, F. P., Coudé, F. X. & Kamoun, P. P. (1979). Effect of propionate and pyruvate on citrulline synthesis and ATP content in rat liver mitochondria. Biochemical and Biophysical Research Communications 90, 327–332.CrossRefGoogle ScholarPubMed
Demigné, C., Yacoub, C., Morand, C. & Rémésy, C. (1988). Orientation of the intermediary metabolism in ruminants (in French). Reproduction, Nutrition, Developpement 28, 1–17.CrossRefGoogle Scholar
Demigné, C., Yacoub, C., Rémésy, C. & Fafournoux, P. (1986). Propionate and butyrate metabolism in rat or sheep hepatocytes. Biochimica et Biophysica Acta 875, 535–542.CrossRefGoogle ScholarPubMed
Emmanuel, B. & Kenelly, J. J. (1984). Effect of propionic acid on ketogenesis in lactating sheep fed restricted rations or deprived of food. Journal of Dairy Science 67, 344–350.CrossRefGoogle ScholarPubMed
Fafournoux, P., Rémésy, C. & Demigné, C. (1983). Control of alanine metabolism in rat liver by transport processes or cellular metabolism. Biochemical Journal 210, 645–652.CrossRefGoogle ScholarPubMed
Faulkner, A. & Pollock, H. T. (1986). Propionate metabolism and its regulation by fatty acids in ovine hepatocytes. Comparative Biochemistry and Physiology 84B, 559–563.Google Scholar
Gill, W., Mitchell, G. E., Boling, J. A., Tucker, R. E., Schelling, G. T., & DeGregorio, R. M. (1985). Glucagon influence on gluconeogenesis and oxidation of propionic acid and threonine by perfused ovine liver. Journal of Dairy Science 68, 2886–2894.Google Scholar
Harmon, D. L., Britton, R. A. & Prior, R. L. (1984). In vitro rates of oxidation and gluconeogenesis from l(+)- and d(−)-lactate in bovine tissues. Comparative Biochemistry and Physiology 77B, 365–368.Google Scholar
Hayes, M. R. & McGivan, J. D. (1982). Differential effects of starvation on alanine and glutamine transport in isolated rat hepatocytes. Biochemical Journal 204, 365–368.CrossRefGoogle ScholarPubMed
Heitmann, R. N. & Bergman, E. N. (1980). Integration of amino acid metabolism in sheep: effects of fasting and acidosis. American Journal of Physiology 239, E248–E254.Google ScholarPubMed
Herriman, I. D. & Heitzman, R. J. (1978). The effects of fasting on the concentrations of intermediate metabolites in the blood and hepatic tissues of pregnant and non-pregnant ewes. Journal of Agricultural Science 90, 579–585.CrossRefGoogle Scholar
Huntington, G. B., Prior, R. L. & Britton, R. A. (1981). Glucose and lactate absorption and metabolic interrelationship in steers changed from low to high concentrate diets. Journal of Nutrition 111, 1164–1172.CrossRefGoogle ScholarPubMed
Judson, G. J., Anderson, E. E., Luick, J. R. & Leng, R. A. (1968). The contribution of propionate to glucose synthesis in sheep given different diets of different grain contents. British Journal of Nutrition 22, 69–74.CrossRefGoogle Scholar
Krebs, H. A., Cornell, N. W., Lund, P. & Hems, R. (1974). Isolated liver cells as an experimental material. In Regulation of Hepatic Metabolism, pp. 726–750 [Lundquist, F. and Tygstrup, N., editors]. Copenhagen: Munksgaard.Google Scholar
Lund, P. & Watford, M. (1976). Glutamine as a precursor of urea. In The Urea Cycle, pp. 479–491 [Grisolia, S., Baguena, R. and Mayor, F., editors]. London: J. Wiley.Google Scholar
Martin, R. J., Wilson, L. L., Crown, R. L. & Sink, J. D. (1973). Effects of fasting and diet on enzyme profiles in ovine liver and adipose tissue. Journal of Animal Science 36, 101–106.CrossRefGoogle ScholarPubMed
Marsh, D. J., Frasier, B. & Decter, J. (1965). Measurements of urea concentration in nanoliter specimens of renal fluid and capillary blood. Analytical Biochemistry 70, 241–250.Google Scholar
Messmer, T. O., Wang, E., Stevens, V. L. & Merrill, A. H. (1989). Sphingolipid biosynthesis by rat liver cells: effects of serine, fatty acids and lipoproteins. Journal of Nutrition 119, 534–538.Google Scholar
Naylor, J. M., Kronfeld, D. S., Freeman, D. E. & Richardson, D. (1984). Hepatic and extrahepatic lactate metabolism in sheep: effect of lactate loading and pH. American Journal of Physiology 247, E747–E755.Google ScholarPubMed
Rattenbury, J. M., Kenwright, A. M., Withers, C. J. & Shepherd, D. A. L. (1983). Effect of propionic acid on urea synthesis by sheep liver. Research in Veterinary Science 35, 61–63.Google Scholar
Rémésy, C. & Demigné, C. (1974). Determination of volatile fatty acids in plasma after ethanolic extraction. Biochemical Journal 141, 85–91.CrossRefGoogle ScholarPubMed
Rémésy, C., Morand, C., Demigné, C. & Fafournoux, P. (1988). Control of hepatic utilization of glutamine by transport processes or cellular metabolism in rats fed a high protein diet. Journal of Nutrition 118, 569–578.Google Scholar
Reynolds, P. J. & Huntington, G. B. (1988). Net portal absorption of volatile fatty acids and L(+)-lactate by lactating Holstein cows. Journal of Dairy Science 71, 124–133.CrossRefGoogle ScholarPubMed
Ricks, C. A. & Cook, R. M. (1981). Regulation of volatile fatty acid uptake by mitochondrial acylCoA synthetases of bovine liver. Journal of Dairy Science 64, 2324–2335.CrossRefGoogle Scholar
Riou, J. P., Audigier, C., Laville, M., Pigeon, P. & Mornex, R. (1985). Dephosphorylation of L-pyruvate kinase during rat liver hepatocyte isolation. Archives of Biochemistry and Biophysics 236, 321–327.CrossRefGoogle ScholarPubMed
Siess, E. A., Brocks, D. G., Lattke, H. K. & Wieland, O. H. (1977). Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochemical Journal 166, 225–235.CrossRefGoogle ScholarPubMed
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. H., Goeke, N. M., Olson, B. J. & Klenk, D. C. (1985). Measurement of protein using bicinchoninic acid. Analytical Biochemistry 150, 76–85.CrossRefGoogle ScholarPubMed
Smith, R. M. (1971). Interactions of acetate, propionate and butyrate in sheep liver mitochondria. Biochemical Journal 124, 877–881.CrossRefGoogle ScholarPubMed
Smith, R. M. & Osborne-White, W. S. (1971). Synthesis of phosphoenolpyruvate from propionate in sheep liver. Biochemical Journal 124, 867–876.CrossRefGoogle ScholarPubMed
Smith, R. W. & Walsh, A. (1982). Effects of pregnancy and lactation on the activities in sheep liver of some enzymes of glucose metabolism. Journal of Agricultural Science, Cambridge 98, 563–565.CrossRefGoogle Scholar
Snedecor, G. & Cochran, W. (1967). Méthodes Statisques, translation of the 6th ed. Paris: Association de Coordination Technique Agricole.Google Scholar
Snell, K. (1980). Liver enzymes of serine metabolism during neonatal development of the rat. Biochemical Journal 190, 451–455.Google Scholar
Veenhuizen, J. J., Russell, R. W. & Young, J. W. (1988). Kinetics of metabolism of glucose, propionate and CO2 in steers as affected by injecting phlorizin and feeding propionate. Journal of Nutrition 118, 1366–1375.CrossRefGoogle ScholarPubMed
Vernon, R. G., Faulkner, A., Finley, E., Pollock, H. & Taylor, E. (1987). Enzymes of glucose and fatty acid metabolism of liver, kidney, skeletal muscle, adipose tissue and mammary gland of lactating and non-lactating sheep. Journal of Animal Science 64, 1395–1411.CrossRefGoogle ScholarPubMed
Wahle, K. W. J., Livesey, C. T. & Scaife, J. R. (1981). Effect of dietary monensin on aspects of propionate metabolism and lipogenesis in sheep. In Metabolic Disorders in Farm Animals pp. 131–134 [Giesecke, D., Dirksen, G. and Stangassinger, M., editors]. Munich: Fotodruck.Google Scholar
Weekes, T. E. C., Richardson, R. I. & Geddes, N. (1978). The effect of ammonia on gluconeogenesis by isolated sheep liver cells. Proceedings of the Nutrition Society 38, 3A.Google Scholar
Wiltrout, D. W. & Satter, L. D. (1972). Contribution of propionate to glucose synthesis in the lactating and the non-lactating cow. Journal of Dairy Science 55, 307–317.CrossRefGoogle Scholar
Zaleski, J., Wilson, D. F. & Erecinska, M. (1986). β-2-Aminobicylo-(2.2.1)-heptane-2-carboxylic acid. A new activator of glutaminase in intact rat liver mitochondria. Journal of Biological Chemistry 216, 14091–14094.CrossRefGoogle Scholar