title: Carnosine promotes the heat denaturation of glycated protein.
abstract: Glycation alters protein structure and decreases biological activity. Glycated proteins, which accumulate in affected tissue, are reliable markers of disease. Carnosine, which prevents glycation, may also play a role in the disposal of glycated protein. Carnosinylation tags glycated proteins for cell removal. Since thermostability determines cell turnover of proteins, the present study examined carnosine's effect on thermal denaturation of glycated protein using cytosolic aspartate aminotransferase (cAAT). Glycated cAAT (500 microM glyceraldehyde for 72h at 37 degrees C) increased the T(0.5) (temperature at which 50% denaturation occurs) and the Gibbs free energy barrier (DeltaG) for denaturation. The enthalpy of denaturation (DeltaH) for glycated cAAT was also higher than that for unmodified cAAT, suggesting that glycation changes the water accessible surface. Carnosine enhanced the thermal unfolding of glycated cAAT as evidenced by a decreased T(0.5) and a lowered Gibbs free energy barrier. Additionally, carnosine decreased the enthalpy of denaturation, suggesting that carnosine may promote hydration during heat denaturation of glycated protein.
authors.affiliation: Department of Biochemistry, University of Health Sciences, 1750 Independence Avenue, Kansas City, MO 64106-1453, USA.
authors.forename: George S
authors.initials: GS
authors.lastname: Yeargans
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Seidler
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry; D002336:Carnosine / Q000737:chemistry*; D004795:Enzyme Stability; D005985:Glyceraldehyde; D006023:Glycoproteins / Q000737:chemistry*; D006031:Glycosylation; D006358:Hot Temperature; D066298:In Vitro Techniques; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D013552:Swine; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D014867:Water; D005985:Glyceraldehyde; D002336:Carnosine; D001219:Aspartate Aminotransferases