Abstract
An alteration in acid-base balance has wide-ranging effects on many systems in the body. It has long been recognized that acid-base regulation is linked to nitrogen metabolism. Ammonium (NH4 +), which is a constituent of normal urine, is excreted in greater quantities in metabolic acidosis. Earlier work showed that the rise in NH4 + excretion in acidosis coincided with a decrease in the rate of urea excretion. When it was realized that the enzyme urease was lacking in mammalian tissues, it was concluded that urea is not a direct source of urinary NH4 +. The discovery that the extraction of glutamine by the kidney contributed significantly to urinary NH4 + focused attention on the renal metabolism of glutamine. It is now well established that the extraction of glutamine by the kidney and the renal mitochondrial deamidation of glutamine are accelerated in chronic metabolic acidosis.
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References
D.E. Atkinson and M. Camien. The role of urea synthesis in the removal of metabolic bicarbonate and the regulation of blood pH. Curr. Top. Cell. Regul. 21:261–302 (1982).
D.E. Atkinson and E. Bourke. The role of ureagenesis in pH homeostasis. Trends Biochem. Sci. 7:297–300 (1984).
J. Oliver, A.M. Koelz, J. Costello, and E. Bourke. Acid-base alterations in glutamine metabolism and ureagenesis in perfused muscle and liver of the rat. Eur. J. Clin. Invest. 7:445–449 (1977).
D. Haussinger, H. Sies, and W. Gerok. Functional heterogeneity in ammonia metabolism. The intercellular glutamine cycle. J. Hepatol. 1:3–14 (1984).
M. L. Halperin, C.B. Chen, S. Cheema-Dhadli, M.L. West, and R.L. Jungas. Is urea formation regulated primarily by acid-base balance in vivo? Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19):F605–F612 (1986).
C. Lenzen, S. Soboll, H. Sies, and D. Haussinger. pH control of hepatic glutamine degradation. Role of transport. Eur. J. Biochem. 166:483–488 (1987).
L. Boon and A.J. Meijer. Control by pH of urea synthesis in isolated hepatocytes. Eur. J Biochem. 172:465–469, 1988.
B. Carey, C.W. Cheung, N.S. Cohen, S. Brusilow, and L. Raijman. Regulation of urea and citrulline synthesis under physiological conditions. Biochem. J. 292:241–247 (1993).
V. Felipo, M-D Minana, and S. Grisolia. Long-term ingestion of ammonium increases acetyl glutamate and urea levels without affecting the amount of carbamoyl-phosphate synthase. Eur. J. Biochem. 176:567–571 (1988).
H.E.S.J. Hensgens, A.J. Verhoeven, and A.J. Meijer. The relationship between intramitochondrial n-acetylglutamine activity and carbamoyl phosphate synthetase (ammonia). Eur. J. Biochem. 107:197–205 (1980).
K. Shigesada, K. Aoyagi, and M. Tatibana. Role of n-acetylglutamate in ureotelism. Variations in acetylglutamate level and its possible significance in control of urea synthesis in mammalian liver. Eur. J. Biochem. 85:385–391 (1978).
N.S. Cohen, S.W. Cheung, and L. Raijman. The effects of ornithine on mitochondrial carbamoyl phosphate synthesis. J. Biol. Chem. 255:10248–10255 (1980).
V. Felipo, M-D Minana, and S. Grisolia. Control of urea synthesis and ammonia utilization in protein deprivation and refeeding. Arch. Biochem. Biophys. 285:351–356 (1991).
T. Saheki, M. Tsuda, T. Tanaka, and N. Katunuma. Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. J Biochem. 77:671–678 (1975).
T. Saheki, T. Katsunuma, and M. Sase. Regulation of urea synthesis in rat liver. Changes in ornithine and n-acetylglutamate concentration in the livers of rats subjected to dietary transitions. J. Biol. Chem. 237:459–468 (1977).
R.T. Schimke. Differential effects of fasting and protein-free diets on levels of urea cycle enzymes in rat liver. J. Biol. Chem. 237:1921–1924 (1962)
R. Zaragosa, J. Renu-Piqueras, M. Portoles, J. Hernandez-Yago, A. Jorda, and S. Grisolia. Rats fed prolonged high protein diets show an increase in nitrogen metabolism and liver megamitochondria. Arch. Biochem. Biophys. 258:426–435 (1987).
L. Boon, P.J.E. Blommaart, A.J. Meijer, W.H. Lamers, and A.C. Schoolwerth. Acute acidosis inhibits amino acid transport: no primary role for the urea cycle in acid-base balance. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36):F1015–F1020 (1994).
L. Boon, P.J.E. Blommaart, A.J. Meijer, W.H. Lamers, and A.C. Schoolwerth. Response of hepatic amino acid consumption to chronic metabolic acidosis. Am. J. Physiol. 271 (Renal Fluid Electrolyte Physiol. 40):F198–F202 (1996).
L. Boon, P.J.E. Blommaart, A.J. Meijer, W.H. Lamers, and A.C. Schoolwerth. Effect of chronic acidosis on hepatic amino acid uptake and gene regulation: implications for control of acid-base balance. Contr. Nephrol. 110:138–143 (1994).
T.C. Welbourne, D. Childress, and G. Givens. Renal regulation of interorgan glutamine flow in metabolic acidosis. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20):R858–R866 (1986).
R.C. May, R.A. Kelly, and W.E. Mitch. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid dependent mechanism. J. Clin. Invest. 77:614–621 (1986).
R.C. May, T. Masud, B. Logue, J. Bailey, and B.K. England. Metabolic acidosis accelerates whole body protein degradation and leucine oxidation by a glucocorticoid dependent mechanism. Miner. Electrolyte Metab. 18:245–249 (1992).
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Schoolwerth, A.C., O’Donovan, D.J. (1997). Effects of Acid-Base Alterations and Protein Depletion on Hepatic Nitrogen Metabolism. In: Felipo, V., Grisolía, S. (eds) Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy. Advances in Experimental Medicine and Biology, vol 420. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5945-0_14
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DOI: https://doi.org/10.1007/978-1-4615-5945-0_14
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