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Chemical Compound Review

MOLI001810     urea

Synonyms: MOLI001869, AC1L9PH1
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Disease relevance of urea

  • Familial azotemia. Impaired urea excretion despite normal renal function [1].
  • Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis [2].
  • These observations indicate that Reye's syndrome is associated with acquired and transient dysfunction of hepatic mitochondrial urea-cycle enzymes [3].
  • CONCLUSIONS: Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema [4].
  • Microencapsulated genetically engineered live E. coli DH5 cells administered orally to maintain normal plasma urea level in uremic rats [5].

Psychiatry related information on urea


High impact information on urea

  • Their levels correlate with extracellular NaCl concentration and, in the case of GPC, also with urea [11].
  • The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function [12].
  • The mean serum albumin concentration was 3.8 +/- 0.4 g per deciliter, the mean urea-reduction value was 62 +/- 4.8 percent, and the mean transferrin saturation was 20 +/- 9 percent [13].
  • A logistic-regression analysis indicated that an 11 percent increase in the urea-reduction value doubled the odds that a patient would have a hematocrit above 30 percent [13].
  • The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups [14].

Chemical compound and disease context of urea

  • Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance [15].
  • Septic encephalopathic patients had elevated serum urea nitrogen and bilirubin levels, increased APACHE II scores, and a higher incidence of renal failure [16].
  • Changes in arterial pH and bicarbonate, or in the concentrations of Na+, K+, urea, or creatinine in plasma or cerebrospinal fluid were similar in uremic animals with intact parthyroid glands and in previously parathyroidectomized uremia dogs [17].
  • Genetic polymorphism in the beta-subunit of the eighth component of human complement, C8, was defined by isoelectric focusing of serum in polyacrylamide gel in the presence of urea and development of specific patterns of hemolysis in an overlay gel containing antibody-sensitized erythrocytes and C8 beta-chain-deficient serum [18].
  • Renal glutamine uptake and subsequent urinary ammonia excretion could be an important alternative pathway of ammonia disposal from the body during liver failure (diminished urea synthesis), but this pathway has received little attention [19].

Biological context of urea


Anatomical context of urea

  • The state of chick embryo chondroblasts in culture was found to be sensitive to both fibronectin and another substance(s) (activity A) which could be extracted from chick embryo fibroblasts with 1 M urea or from conditioned medium [24].
  • Movement of urea across cell membranes was originally thought to occur by lipid-phase permeation, but recent studies have revealed the existence of specialized transporters with a low affinity for urea (Km > 200 mM)2 [25].
  • Recently, we demonstrated that PHF from human cerebral cortex are large, rigid polymers with unusual molecular properties, including insolubility in SDS, urea and other denaturing solvents and apparent resistance to protease digestion [26].
  • It is reported here that isolated liver cells of two teleost toadfishes, Opsanus beta and Opsansus tau, synthesize urea by the ornithine-urea cycle at substantial rates [27].
  • Expression of UreI in Xenopus oocytes results in acid-stimulated urea uptake, with a pH profile similar to activation of cytoplasmic urease [28].

Associations of urea with other chemical compounds

  • Replacement of glucagon raised glucagon to 272 +/- 30 pg per milliliter, glucose to 202 +/- 20 mg per deciliter, glucose excretion to 14 +/- 7 g per 24 hours, ketone excretion to 0.8 mmol per 24 hours and urea nitrogen excretion to 11 +/- 2 g per 24 hours [29].
  • In other tissues that lack a complete urea cycle, arginase regulates cellular arginine and ornithine concentrations for biosynthetic reactions, including nitric oxide synthesis: in the macrophage, arginase activity is reciprocally coordinated with that of NO synthase to modulate NO-dependent cytotoxicity [30].
  • Here we report the isolation of a complementary DNA from rabbit renal medulla that encodes a 397-amino-acid membrane glycoprotein, UT2, with the functional characteristics of the vasopressin-sensitive urea transporter previously described in in vitro-perfused inner medullary collecting ducts [25].
  • An alternative route that has been explored is the reaction of cyanoacetaldehyde (formed by hydrolysis of cyanoacetylene) with urea [31].
  • Here we show that in concentrated urea solution--such as might have been found in an evaporating lagoon or in pools on drying beaches on the early Earth--cyanoacetaldehyde reacts to form cytosine in yields of 30-50%, from which uracil can be formed by hydrolysis [31].

Gene context of urea

  • Moreover, CCR1(-/-) mice developed more severe glomerulonephritis than did controls, with greater proteinuria and blood urea nitrogen, as well as a higher frequency of crescent formation [32].
  • NF-kappaB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea [33].
  • Furthermore, the observation of stable filaments in 4 and 6 M urea suggests that epidermal keratins K1, K2, and K10/11, which ultimately form the bulk of the protective, nonviable stratum corneum, may comprise filaments that are unusually resistant to denaturation [34].
  • Only keratins K5, K14, and K15, which are synthesized by epidermal basal cells, were solubilized in 2 M urea [34].
  • When fractionated by gel electrophoresis in the presence of urea, the ASGP receptor binding polypeptide displayed a characteristic shift in electrophoretic mobility identifying it as the beta adaptin [35].

Analytical, diagnostic and therapeutic context of urea


  1. Familial azotemia. Impaired urea excretion despite normal renal function. Hsu, C.H., Kurtz, T.W., Massari, P.U., Ponze, S.A., Chang, B.S. N. Engl. J. Med. (1978) [Pubmed]
  2. Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis. Brusilow, S.W., Danney, M., Waber, L.J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C., Ward, J. N. Engl. J. Med. (1984) [Pubmed]
  3. Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome. Brown, T., Hug, G., Lansky, L., Bove, K., Scheve, A., Ryan, M., Brown, H., Schubert, W.K., Partin, J.C., Lloyd-Still, J. N. Engl. J. Med. (1976) [Pubmed]
  4. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Glaser, N., Barnett, P., McCaslin, I., Nelson, D., Trainor, J., Louie, J., Kaufman, F., Quayle, K., Roback, M., Malley, R., Kuppermann, N. N. Engl. J. Med. (2001) [Pubmed]
  5. Microencapsulated genetically engineered live E. coli DH5 cells administered orally to maintain normal plasma urea level in uremic rats. Prakash, S., Chang, T.M. Nat. Med. (1996) [Pubmed]
  6. Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Selkoe, D.J., Ihara, Y., Salazar, F.J. Science (1982) [Pubmed]
  7. Prevention of prednisone-induced negative nitrogen balance. Effect of dietary modification on urea generation rate in patients on hemodialysis receiving high-dose glucocorticoids. Cogan, M.G., Sargent, J.A., Yarbrough, S.G., Vincenti, F., Amend, W.J. Ann. Intern. Med. (1981) [Pubmed]
  8. Dysregulation of C/EBP{alpha} by mutant Huntingtin causes the urea cycle deficiency in Huntington's disease. Chiang, M.C., Chen, H.M., Lee, Y.H., Chang, H.H., Wu, Y.C., Soong, B.W., Chen, C.M., Wu, Y.R., Liu, C.S., Niu, D.M., Wu, J.Y., Chen, Y.T., Chern, Y. Hum. Mol. Genet. (2007) [Pubmed]
  9. Beta-amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Wiltfang, J., Esselmann, H., Smirnov, A., Bibl, M., Cepek, L., Steinacker, P., Mollenhauer, B., Buerger, K., Hampel, H., Paul, S., Neumann, M., Maler, M., Zerr, I., Kornhuber, J., Kretzschmar, H.A., Poser, S., Otto, M. Ann. Neurol. (2003) [Pubmed]
  10. Minimum urine flow rate during water deprivation: importance of the nonurea versus total osmolality in the inner medulla. Soroka, S.D., Chayaraks, S., Cheema-Dhadli, S., Myers, J.A., Rubin, S., Sonnenberg, H., Halperin, M.L. J. Am. Soc. Nephrol. (1997) [Pubmed]
  11. Renal medullary organic osmolytes. Garcia-Perez, A., Burg, M.B. Physiol. Rev. (1991) [Pubmed]
  12. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Kobayashi, K., Sinasac, D.S., Iijima, M., Boright, A.P., Begum, L., Lee, J.R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M.A., Kondo, I., Tsui, L.C., Scherer, S.W., Saheki, T. Nat. Genet. (1999) [Pubmed]
  13. The intensity of hemodialysis and the response to erythropoietin in patients with end-stage renal disease. Ifudu, O., Feldman, J., Friedman, E.A. N. Engl. J. Med. (1996) [Pubmed]
  14. Endoscopic biliary drainage for severe acute cholangitis. Lai, E.C., Mok, F.P., Tan, E.S., Lo, C.M., Fan, S.T., You, K.T., Wong, J. N. Engl. J. Med. (1992) [Pubmed]
  15. Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. Batshaw, M., Brusilow, S., Walser, M. N. Engl. J. Med. (1975) [Pubmed]
  16. The spectrum of septic encephalopathy. Definitions, etiologies, and mortalities. Eidelman, L.A., Putterman, D., Putterman, C., Sprung, C.L. JAMA (1996) [Pubmed]
  17. Changes in the electroencephalogram in acute uremia. Effects of parathyroid hormone and brain electrolytes. Guisado, R., Arieff, A.I., Massry, S.G., Lazarowitz, V., Kerian, A. J. Clin. Invest. (1975) [Pubmed]
  18. Genetic polymorphism in C8 beta-chains. Evidence for two unlinked genetic loci for the eighth component of human complement (C8). Alper, C.A., Marcus, D., Raum, D., Petersen, B.H., Spira, T.J. J. Clin. Invest. (1983) [Pubmed]
  19. Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat. Dejong, C.H., Deutz, N.E., Soeters, P.B. J. Clin. Invest. (1993) [Pubmed]
  20. Natural history of symptomatic partial ornithine transcarbamylase deficiency. Rowe, P.C., Newman, S.L., Brusilow, S.W. N. Engl. J. Med. (1986) [Pubmed]
  21. The complete sequence of the mucosal pathogen Ureaplasma urealyticum. Glass, J.I., Lefkowitz, E.J., Glass, J.S., Heiner, C.R., Chen, E.Y., Cassell, G.H. Nature (2000) [Pubmed]
  22. Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis. Brusilow, S., Tinker, J., Batshaw, M.L. Science (1980) [Pubmed]
  23. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group. Viberti, G., Mogensen, C.E., Groop, L.C., Pauls, J.F. JAMA (1994) [Pubmed]
  24. Fibronectin alters the phenotypic properties of cultured chick embryo chondroblasts. West, C.M., Lanza, R., Rosenbloom, J., Lowe, M., Holtzer, H., Avdalovic, N. Cell (1979) [Pubmed]
  25. Cloning and characterization of the vasopressin-regulated urea transporter. You, G., Smith, C.P., Kanai, Y., Lee, W.S., Stelzner, M., Hediger, M.A. Nature (1993) [Pubmed]
  26. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Ihara, Y., Abraham, C., Selkoe, D.J. Nature (1983) [Pubmed]
  27. Evolution of urea synthesis in vertebrates: the piscine connection. Mommsen, T.P., Walsh, P.J. Science (1989) [Pubmed]
  28. A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Weeks, D.L., Eskandari, S., Scott, D.R., Sachs, G. Science (2000) [Pubmed]
  29. Hyperglucagonemia and its suppression. Importance in the metabolic control of diabetes. Raskin, P., Unger, R.H. N. Engl. J. Med. (1978) [Pubmed]
  30. Structure of a unique binuclear manganese cluster in arginase. Kanyo, Z.F., Scolnick, L.R., Ash, D.E., Christianson, D.W. Nature (1996) [Pubmed]
  31. An efficient prebiotic synthesis of cytosine and uracil. Robertson, M.P., Miller, S.L. Nature (1995) [Pubmed]
  32. Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis. Topham, P.S., Csizmadia, V., Soler, D., Hines, D., Gerard, C.J., Salant, D.J., Hancock, W.W. J. Clin. Invest. (1999) [Pubmed]
  33. Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells. Hao, C.M., Yull, F., Blackwell, T., Kömhoff, M., Davis, L.S., Breyer, M.D. J. Clin. Invest. (2000) [Pubmed]
  34. Differential extraction of keratin subunits and filaments from normal human epidermis. Eichner, R., Kahn, M. J. Cell Biol. (1990) [Pubmed]
  35. In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles. Beltzer, J.P., Spiess, M. EMBO J. (1991) [Pubmed]
  36. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. Owen, W.F., Lew, N.L., Liu, Y., Lowrie, E.G., Lazarus, J.M. N. Engl. J. Med. (1993) [Pubmed]
  37. Is blood urea nitrogen as good a guide for hemofiltration as for hemodialysis? De Fremont, J.F., Coevoet, B., Dkhissi, H., Pruna, A., Moriniere, P., Galy, C., Fournier, A. N. Engl. J. Med. (1982) [Pubmed]
  38. Salivary gland hyperglycemic factor: an extrapancreatic source of glucagon-like material. Lawrence, A.M., Tan, S., Hojvat, S., Kirsteins, L. Science (1977) [Pubmed]
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