Carbamylation of proteins – mechanism, causes and consequences
Anna Pieniążek 1 , Krzysztof Gwoździński 2Abstract
Carbamylation (carbamoylation) is a post-translational modification resulting from the nonenzymatic reaction between isocyanic acid and free functional groups of proteins, in particular with the free amino groups. This reaction alters structural and functional properties of proteins and results in faster aging of proteins.Urea present in the body can be transformed into cyanate and its more reactive form, isocyanic acid. High concentration of urea is associated with some diseases, especially with chronic renal failure and atherosclerosis. In human tissues, urea and cyanate are in equilibrium in aqueous solutions. Surprisingly, concentration of isocyanate in the body is much lower than it would appear from the kinetic parameters of urea decomposition. The low concentration of isocyanic acid results from its high reactivity and short half-life.In this review we describe the biochemical mechanism of carbamylation of proteins and freeamino acids. We summarize the literature data for carbamylation of hemoglobin, lipoproteins,albumin, membrane proteins and erythropoietin in chronic renal failure.In summary, the carbamylation of proteins may have a negative impact on their biologicalactivity and may contribute to the deterioration of patients with chronic renal failure.
References
- 1. Albert C., Mertens P.R., Bartsch P.: Urea and atherosclerosis – evidencefor a direct link involving apolipoprotein B protein modifications.Int. Urol. Nephrol., 2011; 43: 933-936
Google Scholar - 2. Apostolov E.O., Basnakian A.G., Ok E., Shah S.V.: Carbamylatedlow-density lipoprotein: nontraditional risk factor for cardiovascularevents in patients with chronic kidney disease. J. Ren. Nutr.,2012; 22: 134-138
Google Scholar - 3. Apostolov E.O., Ray D., Savenka A.V., Shah S.V., Basnakian A.G.:Chronic uremia stimulates LDL carbamylation and atherosclerosis.J. Am. Soc. Nephrol., 2010; 21: 1852-1857
Google Scholar - 4. Arlandson M., Decker T., Roongta V.A., Bonilla L., Mayo K.H.,MacPherson J.C., Hazen S.L., Slungaard A.: Eosinophil peroxidaseoxidation of thiocyanate. Characterization of major reaction productsand a potential sulfhydryl-targeted cytotoxicity system. J. Biol.Chem., 2001; 276: 215-224
Google Scholar - 5. Berg A.H., Drechsler C., Wenger J., Buccafusca R., Hod T., Kalim S.,Ramma W., Parikh S.M., Steen H., Friedman D.J., Danziger J., WannerC., Thadhani R., Karumanchi S.A.: Carbamylation of serum albuminas a risk factor for mortality in patients with kidney failure. Sci.Transl. Med., 2013; 5: 175ra29
Google Scholar - 6. Brouillette C.G., Anantharamaiah G.M., Engler J.A., Borhani D.W.:Structural models of human apolipoprotein A-I: a critical analysisand review. Biochim. Biophys. Acta, 2001; 1531: 4-46
Google Scholar - 7. Brzeszczynska J., Luciak M., Gwozdzinski K.: Alterations of erythrocytestructure and cellular susceptibility in patients with chronicrenal failure: effect of haemodialysis and oxidative stress. Free Radic.Res., 2008; 42: 40-48
Google Scholar - 8. Davies M.J.: Myeloperoxidase-derived oxidation: mechanismsof biological damage and its prevention. J. Clin. Biochem. Nutr.,2011; 48: 8-19
Google Scholar - 9. Ghaffari M.A., Shanaki M.: Evalution of in vitro effect of flavonoidson human low-density lipoprotein carbamylation. Iran. J. Pharm.Res., 2010; 9: 67-74
Google Scholar - 10. Gillery P.: Nonenzymatic post-translational modification derivedproducts: new biomarkers of protein aging. J. Med. Biochem.,2011; 30: 201-206
Google Scholar - 11. Gołębiowska-Staroszczyk S., Matysiak M., Adamowicz-SalachA., Albrecht-Stanisławska K., Sobocińska-Mirska A.: Erytropoetyna– alternatywne leczenie niedokrwistości u niemowląt. Hematologia,2011; 2: 71-82
Google Scholar - 12. Gonzalez P., Grisolia S.: Carbamylation of glutamate dehydrogenaseand other mitochondrial proteins by biosynthetic carbamylphosphate. Physiol. Chem. Phys., 1975; 7: 271-275
Google Scholar - 13. Hamouda A.R., Nabih E.S., Khalek S.A.: Novel equation for correctionof glycated hemoglobin and calculation of carbamylated hemoglobinin diabetic uremic patients. Res. J. Chem. Sci., 2013; 3: 6-11
Google Scholar - 14. Holzer M., Gauster M., Pfeifer T., Wadsack C., Fauler G., StieglerP., Koefeler H., Beubler E., Schuligoi R., Heinemann A., Marsche G.:Protein carbamylation renders high-density lipoprotein dysfunctional.Antioxid. Redox Signal., 2011; 14: 2337-2346
Google Scholar - 15. Hörkkö S., Huttunen K., Kervinen K., Kesäniemi Y.A.: Decreasedclearance of uraemic and mildly carbamylated low-density lipoprotein.Eur. J. Clin. Invest., 1994; 24: 105-113
Google Scholar - 16. Jaisson S., Delevallée-Forte C., Touré F., Rieu P., Garnotel R., GilleryP.: Carbamylated albumin is a potent inhibitor of polymorphonuclearneutrophil respiratory burst. FEBS Lett., 2007; 581: 1509-1513
Google Scholar - 17. Jaisson S., Gillery P.: Evaluation of nonenzymatic posttranslationalmodification-derived products as biomarkers of molecularaging of proteins. Clin. Chem., 2010; 56: 1401-1412
Google Scholar - 18. Jaisson S., Lorimier S., Ricard-Blum S., Sockalingum G.D., Delevallée-ForteC., Kegelaer G., Manfait M., Garnotel R., Gillery P.: Impactof carbamylation on type I collagen conformational structureand its ability to activate human polymorphonuclear neutrophils.Chem. Biol., 2006; 13: 149-159
Google Scholar - 19. Jaisson S., Pietrement C., Gillery P.: Carbamylation-derived products:bioactive compounds and potential biomarkers in chronic renalfailure and atherosclerosis. Clin. Chem., 2011; 57: 1499-1505
Google Scholar - 20. Jin K.: Effects of amino acids and albumin on erythropoietincarbamoylation. Clin. Exp. Nephrol., 2013; 17: 575-581
Google Scholar - 21. Kairaitis L.K., Yuill E., Harris D.C.: Determinants of haemoglobincarbamylation in haemodialysis and peritoneal dialysis patients.Nephrol. Dial. Transplant., 2000; 15: 1431-1437
Google Scholar - 22. Kalim S., Karumanchi S.A., Thadhani R.I., Berg A.H.: Proteincarbamylation in kidney disease: pathogenesis and clinical implications.Am. J. Kidney Dis., 2014; 64: 793-803
Google Scholar - 23. Kok M.B., Tegelaers F.P., van Dam B., van Rijn J.L., van Pelt J.:Carbamylation of albumin is a cause for discrepancies between albuminassays. Clin. Chim. Acta, 2014; 434: 6-10
Google Scholar - 24. Kraus L.M., Jones M.R., Kraus A.P. Jr.: Essential carbamoyl-aminoacids formed in vivo in patients with end-stage renal diseasemanaged by continuous ambulatory peritoneal dialysis: isolation,identification, and quantitation. J. Lab. Clin. Med., 1998; 131: 425-431
Google Scholar - 25. Kraus L.M., Kraus A.P. Jr.: Carbamoylation of amino acids andproteins in uremia. Kidney Int. Suppl., 2001; 78: S102-S107
Google Scholar - 26. Leggio C., Galantini L., Pavel N.V.: About the albumin structurein solution: cigar Expanded form versus heart Normal shape. Phys.Chem. Chem. Phys., 2008; 10: 6741-6750
Google Scholar - 27. Li Q., Ju Y., Jin T., Pang B., Deng J., Du T., Wang H.: HaemoglobinA₁c measurement in patients with chronic kidney disease. Clin.Biochem., 2014; 47: 481-484
Google Scholar - 28. Malyszko J., Malyszko J.S., Pawlak K., Mysliwiec M.: Hepcidin,iron status, and renal function in chronic renal failure, kidney transplantation,and hemodialysis. Am. J. Hematol., 2006; 81: 832-837
Google Scholar - 29. Meerwaldt R., Links T., Zeebregts C., Tio R., Hillebrands J.L., SmitA.: The clinical relevance of assessing advanced glycation endproductsaccumulation in diabetes. Cardiovasc. Diabetol., 2008; 7: 29
Google Scholar - 30. Mun K.C., Golper T.A.: Impaired biological activity of erythropoietinby cyanate carbamylation. Blood Purif., 2000; 18: 13-17
Google Scholar - 31. Mun K.C., Kim H.C., Kwak C.S.: Cyanate as a hemolytic factor.Ren. Fail., 2000; 22: 809-814
Google Scholar - 32. Nilsson L., Lundquist P., Kagedal B., Larsson R.: Plasma cyanateconcentrations in chronic renal failure. Clin. Chem., 1996; 42: 482-483
Google Scholar - 33. Park K.D., Mun K.C., Chang E.J., Park S.B., Kim H.C.: Inhibition of erythropoietinactivity by cyanate. Scand. J. Urol. Nephrol., 2004; 38: 69-72
Google Scholar - 34. Pieniążek A., Brzeszczyńska J., Gwoździński K.: Comparison carbamylationand oxidative damage in membrane proteins in humanerd blood cells. Proceedings of XI Meeting of the Society for FreeRadical Research International. Manduzzi Editore –MEDIMOND,2002; 685-688
Google Scholar - 35. Pieniążek A., Brzeszczyńska J., Kruszyńska I., Gwoździński K.:Investigation of albumin properties in patients with chronic renalfailure. Free Radic. Res., 2009; 43: 1008-1018
Google Scholar - 36. Pieniążek A., Gwoździński K.: Carbamylation of proteins leadsto alterations in the membrane structure of erythrocytes. Cell. Mol.Biol. Lett., 2003; 8: 127-131
Google Scholar - 37. Praschberger M., Hermann M., Laggner C., Jirovetz L., ExnerM., Kapiotis S., Gmeiner B.M., Laggner H.: Carbamoylation abrogatesthe antioxidant potential of hydrogen sulfide. Biochimie., 2013;95: 2069-2075
Google Scholar - 38. Ramponi G., Leaver J.L., Grisolia S.: Homocitrulline formationfollowing carbamylation of histones with carbamyl phosphate. FEBSLett., 1971; 16: 311-314
Google Scholar - 39. Roxborough H.E., Young I.S.: Carbamylation of proteins andatherogenesis in renal failure. Med. Hypotheses, 1995; 45: 125-128
Google Scholar - 40. Said G., Guilbert M., Millerot-Serrurot E., Van Gulick L., TerrynC., Garnotel R., Jeannesson P.: Impact of carbamylation and glycationof collagen type I on migration of HT1080 human fibrosarcomacells. Int. J. Oncol., 2012; 40: 1797-1804
Google Scholar - 41. Segrest J.P., Jones M.K., De Loof H., Dashti N.: Structure of apolipoproteinB-100 in low density lipoproteins. J. Lipid Res., 2001;42: 1346-1367
Google Scholar - 42. Selvaraj N., Bobby Z., Das A.K., Ramesh R., Koner B.C.: An evaluationof level of oxidative stress and protein glycation in nondiabeticundialyzed chronic renal failure patients. Clin. Chim. Acta,2002; 324: 45-50
Google Scholar - 43. Siewiera K., Labieniec-Watala M.: Ambiguous effect of dendrimerPAMAM G3 on rat heart respiration in a model of an experimentaldiabetes – Objective causes of laboratory misfortune or unpredictableG3 activity? Int. J. Pharm., 2012; 430: 258-265
Google Scholar - 44. Sirpal S.: Myeloperoxidase-mediated lipoprotein carbamylationas a mechanistic pathway for atherosclerotic vascular disease. Clin.Sci., 2009; 116: 681-695
Google Scholar - 45. Sun S., Zhou J.Y., Yang W., Zhang H.: Inhibition of protein carbamylationin urea solution using ammonium-containing buffers.Anal. Biochem., 2014; 446: 76-81
Google Scholar - 46. Trepanier D.J., Thibert R.J.: Carbamylation of erythrocyte membraneaminophospholipids: an in vitro and in vivo study. Clin. Biochem.,1996; 29: 333-345
Google Scholar - 47. Trepanier D.J., Thibert R.J., Draisey T.F., Caines P.S.: Carbamylationof erythrocyte membrane proteins: an in vitro and in vivo study.Clin. Biochem., 1996; 29: 347-355
Google Scholar - 48. Vos F.E., Schollum J.B., Coulter C.V., Doyle T.C., Duffull S.B., WalkerR.J.: Red blood cell survival in long-term dialysis patients. Am.J. Kidney Dis., 2011; 58: 591-598
Google Scholar - 49. Wang Z., Nicholls S.J., Rodriguez E.R., Kummu O., Hörkkö S., BarnardJ., Reynolds W.F., Topol E.J., DiDonato J.A., Hazen S.L.: Proteincarbamylation links inflammation, smoking, uremia and atherogenesis.Nat. Med., 2007; 13: 1176-1184
Google Scholar - 50. Wynckel A., Randoux C., Millart H., Desroches C., Gillery P., CanivetE., Chanard J.: Kinetics of carbamylated haemoglobin in acuterenal failure. Nephrol. Dial. Transplant., 2000; 15: 1183-1188
Google Scholar