Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-23T11:54:35.768Z Has data issue: false hasContentIssue false

Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism

Published online by Cambridge University Press:  09 March 2007

G. E. Lobley
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
A. Connell
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
M. A. Lomax
Affiliation:
Department of Biochemistry and Physiology, University of Reading, Reading RG6 2AH
D. S. Brown
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
E. Milne
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
A. G. Calder
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
D. A. H. Farningham
Affiliation:
Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB
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 effects of either low (25 μmol/min) or high (235 μmol/min) infusion of NH4Cl into the mesenteric vein for 5 d were determined on O2 consumption plus urea and amino acid transfers across the portal-drained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of 15NH4Cl for 10 h on the fifth day with simultaneous infusion of [1-13C]lleucine to monitor amino acid oxidation. Neither PDV nor liver blood flow were affected by the additional NH3 loading, although at the higher rate there was a trend for increased liver O2 consumption. NH3-N extraction by the liver accounted for 64–70% of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH3 administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion but both whole-body (P < 0·05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15N]glutamine occurred across the liver, particularly with the greater NH3 supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC 1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamination. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea. The implications of NH3 detoxification to the energy and N metabolism of the ruminant are discussed.

Type
Ammonia kinetics in sheep
Copyright
Copyright © The Nutrition Society 1995

References

Alpers, D. H. (1972). Protein synthesis in intestinal mucosa: the effect of route of administration of precursor amino acids. Journal of Clinical Investigation 51, 167173.CrossRefGoogle ScholarPubMed
Atkinson, D. E. & Bourke, E. (1984) The role of ureagenesis in pH homeostasis. Trends in Biochemical Sciences 9, 297300.CrossRefGoogle Scholar
Attaix, D., Aurousseau, E., Bayle, G., Manghebati, A. & Arnal, M. (1987) Protein synthesis and degradation in growing lambs. In 5th International Symposium on Protein Metabolism and Nutrition. European Association of Animal Production Publication, no. 35, pp. 2427. Rostock: Wilhelm-Pieck University.Google Scholar
Attaix, D., Aurousseau, E., Rosolowska-Huszez, D., Bayle, G. & Arnal, M. (1992) In vivo longitudinal variations in protein synthesis in developing ovine intestines. American Journal of Physiology 263, R1318R1323.Google ScholarPubMed
Ballmer, P. E., McNurlan, M. A., Milne, E., Heys, S. D., Buchan, V., Calder, A. G. & Garlick, P. J. (1990) Measurement of albumin synthesis in humans: a new approach employing stable isotopes. American Journal of Physiology 259, E797E803.Google ScholarPubMed
Bartels, H. & Harms, H. (1959) Saverstoffdissoziationskurven des Blutes von Säugetieren (Mensch, Karinchen, Meerschweinchen, Hund, Katz, Schwein, Rind und Schaf)(Oxygen dissociation curves for blood of mammals (man, rabbit, guinea pig, dog, cat, pig, cattle and sheep). Pflügers Archivs 268, 334365.CrossRefGoogle Scholar
Blaxter, K. L., Brockway, J. M. & Boyne, A. W. (1972) A new method for estimating the heat production of animals. Quarterly Journal of Experimental Physiology 57, 6072.CrossRefGoogle ScholarPubMed
Burrin, D. G., Ferrell, C. L., Britton, R. A. & Bauer, M. (1990) Level of nutrition and visceral organ size and metabolic activity in sheep. British Journal of Nutrition 64, 439448.CrossRefGoogle ScholarPubMed
Burrin, D. G., Ferrell, C. L., Eisemann, J. H., Britton, R. A. & Nienaber, J. A. (1989) Effect of level of nutrition on splanchnic blood flow and oxygen consumption in sheep. British Journal of Nutrition 62, 2334.CrossRefGoogle ScholarPubMed
Cooper, A. J. L., Nieves, E., Coleman, A. E., Filc-De Ricco, S. & Gelbard, A. S. (1987) Short-term metabolic fate of [13N]ammonia in rat liver in vivo. Journal of Biological Chemistry 262, 10731080.CrossRefGoogle ScholarPubMed
Fern, E. B. & Garlick, P. J. (1974) The specific radioactivity of the tissue free amino acid pool as a basis for measuring the rate of protein synthesis in the rat in vivo. Biochemical Journal 142, 413419.CrossRefGoogle Scholar
Fitch, N. A., Gill, M., Lomax, M. A. & Beever, D. E. (1989) Nitrogen and glucose metabolism by the liver of forage- and forage-concentrate-fed cattle. Proceedings of the Nutrition Society 48, 76A.Google Scholar
Fleet, I. R. & Mepham, T. B. (1983) Physiological methods used in the study of mammary substrate utilization in ruminants. In Biochemistry of Lactation, pp. 469491 [Mepham, T. B., editor]. Amsterdam: Elsevier Science Publishers.Google Scholar
Gebhardt, R. & Mecke, D. (1983) Glutamate uptake by cultured rat hepatocytes is mediated by hormonally inducible sodium-dependent transport systems. FEBS Letters 161, 275278.CrossRefGoogle ScholarPubMed
Goodwin, G. W., Gibboney, W., Paxton, R., Harris, R. A. & Lemons, J. A. (1987) Activities of branch-chain amino acid aminotransferase and branch-chain 2-oxo dehydrogenase complex in tissues of maternal and fed sheep. Biochemical Journal 242, 305308.CrossRefGoogle Scholar
Hams, P. M., Skene, P. A., Buchan, V., Calder, A. G., Anderson, S. E., Connell, A. & Lobley, G. E. (1992) Effect of food intake on hind-limb and whole-body protein metabolism in young growing sheep: chronic studies based on arterio-venous techniques. British Journal of Nutrition 68, 389407.Google Scholar
Häussinger, D. (1983) Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intracellular glutamine cycle during ureogenesis in perfused rat liver. European Journal of Biochemistry 133, 269274.CrossRefGoogle ScholarPubMed
Häussinger, D. & Gerok, W. (1983) Hepatocyte heterogeneity in glutamate uptake in isolated perfused rat liver. European Journal of Biochemistry 136, 421425.CrossRefGoogle ScholarPubMed
Häussinger, D. & Gerok, W. (1984) Regulation of hepatic glutamate metabolism. Role of 2-oxoacids in glutamate release from isolated perfused rat liver. European Journal of Biochemistry 143, 491497.CrossRefGoogle ScholarPubMed
Häussinger, D., Lamers, W. H. & Moorman, A. F. M. (1992) Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. Enzyme 46, 7293.CrossRefGoogle Scholar
Heitmann, R. N. & Bergman, E. N. (1981) Glutamate interconversions and glucogenicity in the sheep. American Journal of physiology 241, E465E472.Google ScholarPubMed
Herd, J. A. & Barger, A. C. (1964) Simplified technique for chronic catheterisation of blood vessels. Journal of Applied Physiology 19, 791792.CrossRefGoogle ScholarPubMed
Huntington, G. B. (1989) Hepatic urea synthesis and site and rate of removal from blood of beef steers fed alfalfa or a high concentrate diet. Canadian Journal of Animal Science 69, 215223.CrossRefGoogle Scholar
Huntington, G. B. (1990) Energy metabolism in the digestive tract and liver of cattle: influence of physiological state and nutrition. Reproduction, Nutrition, Developpement 30, 3547.CrossRefGoogle ScholarPubMed
Huntington, G. B. & Reynolds, C. K. (1987) Oxygen consumption and metabolite flux of bovine portal-drained viscera and liver. Journal of Nutrition 117, 11671173.CrossRefGoogle ScholarPubMed
Jungerman, K. & Katz, N. (1989) Functional specialization of different hepatocyte populations. Physiological Reviews 69, 708764.CrossRefGoogle Scholar
Katz, M. L. & Bergman, E. N. (1969 a) A method for simultaneous cannulation of the major splanchnic blood vessels of the sheep. American Journal of Veterinary Research 30, 655661.Google ScholarPubMed
Katz, M. L. & Bergman, E. N. (1969 b) Simultaneous measurements of hepatic and portal venous blood flow in the sheep and dog. American Journal of Physiology 216, 946952.CrossRefGoogle ScholarPubMed
Linzell, J. L., Setchell, B. P. & Lindsay, D. B. (1971) The isolated perfused liver of sheep: assessment of its metabolic, synthetic and secretory functions. Quarterly Journal of Experimental Physiology 56, 5371.CrossRefGoogle Scholar
Lobley, G. E. (1992) Control of the metabolic fate of amino acids in ruminants: a review. Journal of Animal Science 70, 32643275.CrossRefGoogle ScholarPubMed
Lobley, G. E., Connell, A., Milne, E., Newman, A. M. & Ewing, T. A. (1994) Protein synthesis in splanchnic tissue of sheep offered two levels of intake. British Journal of Nutrition 71, 312.CrossRefGoogle ScholarPubMed
Lobley, G. E., Harris, P. M., Skene, P. A., Brown, D., Milne, E., Calder, A. G., Anderson, S. E., Garlick, P. J., Nevison, I. & Connell, A. (1992) Responses in tissue protein synthesis to sub- and supra-maintenance intake in young growing sheep: comparison of large-dose, and continuous-infusion techniques. British Journal of Nutrition 68, 373388.CrossRefGoogle ScholarPubMed
Lobley, G. E., Milne, V., Lovie, J. M., Reeds, P. J. & Pennie, K. (1980) Whole body and tissue protein synthesis in cattle. British Journal of Nutrition 43, 491502.CrossRefGoogle ScholarPubMed
Lowenstein, J. M. (1972) Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiological Reviews 52, 382414.CrossRefGoogle ScholarPubMed
MacRae, J. C., Lobley, G. E., Bruce, L. A., Luo, Q. J., Calder, A. G. & Farningham, D. A. H. (1993) Leucine kinetics across the portal drained viscera of sheep. Journal of Animal Science, Suppl. 71 1, 279 (Abstr.).Google Scholar
Maltby, S. A., Lomax, M. A., Beever, D. E. & Pippard, C. J. (1991) The effect of increased ammonia and amino acid supply on post prandial portal-drained viscera and hepatic metabolism in growing steers fed maize silage. In Energy Metabolism of Farm Animals, European Association for Animal Production Publication, no. 58, pp. 2033 [Wenk, C. and Boessinger, M., editors]. Zurich: Schriftenreche aus dem Institut für Nutztierwissenschaften Gruppe Ernährung.Google Scholar
Marsh, W. H., Fingerhut, B. & Miller, H. (1965) Automated and manual direct methods for the determination of blood urea. Clinical Chemistry 2, 624627.CrossRefGoogle Scholar
May, R. C., Hara, Y., Kelly, A., Block, K. P., Buse, M. G. & Mitch, W. E. (1987) Branched chain amino acid metabolism in rat muscle: abnormal regulation in acidosis. American Journal of Physiology 252, E712E718.Google ScholarPubMed