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. 1976 Nov 15;160(2):205–209. doi: 10.1042/bj1600205

Effect of ornithine and lactate on urea synthesis in isolated hepatocytes.

S Briggs, R A Freedland
PMCID: PMC1164223  PMID: 1008850

Abstract

1. In hepatocytes isolated from 24 h-starved rats, urea production from ammonia was stimulated by addition of lactate, in both the presence and the absence of ornithine. The relationship of lactate concentration to the rate of urea synthesis was hyperbolic. 2. Other glucose precursors also stimulated urea production to varying degrees, but none more than lactate. Added oleate and butyrate did not stimulate urea synthesis. 3. Citrulline accumulation was largely dependent on ornithine concentration. As ornithine was increased from 0 to 40 mM, the rate of citrulline accumulation increased hyperbolically, and was half-maximal when ornithine was 8-12 mM. 4. The rate of citrulline accumulation was independent of the presence of lactate, but with pyruvate the rate increased. 5. The rate of urea production continued to increase as ornithine was varied from 0 to 40 mM. 6. It was concluded that intermediates provided by both ornithine and lactate are limiting for urea production from ammonia in isolated liver cells. It was suggested that the stimulatory effect of lactate lies in increased availability of cytosolic aspartate for condensation with citrulline.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BIRNBAUM S. M., GREENSTEIN J. P., GULLINO P., OTEY M. C., WINITZ M. Studies on the metabolism of amino acids and related compounds in vivo. III. Prevention of ammonia toxicity by arginine and related compounds. Arch Biochem Biophys. 1956 Oct;64(2):342–354. doi: 10.1016/0003-9861(56)90278-8. [DOI] [PubMed] [Google Scholar]
  2. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. FREEDLAND R. A., SODIKOFF C. H. Effect of diets and hormones on two urea cycle enzymes. Proc Soc Exp Biol Med. 1962 Feb;109:394–396. doi: 10.3181/00379727-109-27215. [DOI] [PubMed] [Google Scholar]
  4. Foster L. B., Hochholzer J. M. A single-reagent manual method for directly determining urea nitrogen in serum. Clin Chem. 1971 Sep;17(9):921–925. [PubMed] [Google Scholar]
  5. Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kramer J. W., Freedland R. A. Possible rate-limiting factors in urea synthesis by the perfused rat liver. Proc Soc Exp Biol Med. 1972 Dec;141(3):833–835. doi: 10.3181/00379727-141-36883. [DOI] [PubMed] [Google Scholar]
  7. Krebs H. A., Gascoyne T., Notton B. M. Generation of extramitochondrial reducing power in gluconeogenesis. Biochem J. 1967 Jan;102(1):275–282. doi: 10.1042/bj1020275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McGivan J. D., Bradford N. M., Mendes-Mourão J. The regulation of carbamoyl phosphate synthase activity in rat liver mitochondria. Biochem J. 1976 Feb 15;154(2):415–421. doi: 10.1042/bj1540415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Meijer A. J., Gimpel J. A., Deleeuw G. A., Tager J. M., Williamson J. R. Role of anion translocation across the mitochondrial membrane in the regulation of urea synthesis from ammonia by isolated rat hepatocytes. J Biol Chem. 1975 Oct 10;250(19):7728–7738. [PubMed] [Google Scholar]
  10. Ontko J. A. Metabolism of free fatty acids in isolated liver cells. Factors affecting the partition between esterification and oxidation. J Biol Chem. 1972 Mar 25;247(6):1788–1800. [PubMed] [Google Scholar]
  11. RATNER S. Urea synthesis and metabolism of arginine and citrulline. Adv Enzymol Relat Subj Biochem. 1954;15:319–387. doi: 10.1002/9780470122600.ch8. [DOI] [PubMed] [Google Scholar]
  12. Ratner S. Determination of arginnosuccinate in normal blood serum and liver. Anal Biochem. 1975 Jan;63(1):141–155. doi: 10.1016/0003-2697(75)90198-0. [DOI] [PubMed] [Google Scholar]
  13. Ratner S. Enzymes of arginine and urea synthesis. Adv Enzymol Relat Areas Mol Biol. 1973;39:1–90. doi: 10.1002/9780470122846.ch1. [DOI] [PubMed] [Google Scholar]
  14. Rognstad R., Katz J. Gluconeogenesis in the kidney cortex. Effects of D-malate and amino-oxyacetate. Biochem J. 1970 Feb;116(3):483–491. doi: 10.1042/bj1160483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ross B. D., Hems R., Krebs H. A. The rate of gluconeogenesis from various precursors in the perfused rat liver. Biochem J. 1967 Mar;102(3):942–951. doi: 10.1042/bj1020942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. SCHIMKE R. T. Adaptive characteristics of urea cycle enzymes in the rat. J Biol Chem. 1962 Feb;237:459–468. [PubMed] [Google Scholar]
  17. Saheki T., Katunuma N. Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. I. Urea synthesis with ammonia and glutamine as nitrogen sources. J Biochem. 1975 Mar;77(3):659–669. doi: 10.1093/oxfordjournals.jbchem.a130768. [DOI] [PubMed] [Google Scholar]
  18. Shigesada K., Tatibana M. Role of acetylglutamate in ureotelism. I. Occurrence and biosynthesis of acetylglutamate in mouse and rat tissues. J Biol Chem. 1971 Sep 25;246(18):5588–5595. [PubMed] [Google Scholar]
  19. Stubbs M., Krebs H. A. The accumulation of aspartate in the presence of ethanol in rat liver. Biochem J. 1975 Jul;150(1):41–45. doi: 10.1042/bj1500041. [DOI] [PMC free article] [PubMed] [Google Scholar]

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