Effect of nonenzymatic glycation on functional and structural properties of hemoglobin.
HbA(1c), the major glycated hemoglobin increases proportionately with blood glucose concentration in diabetes mellitus. H(2)O(2) promotes more iron release from HbA(1c) than that from nonglycated hemoglobin, HbA(0). This free iron, acting as a Fenton reagent, might produce free radicals and degrade cell constituents. Here we demonstrate that in the presence of H(2)O(2), HbA(1c) degrades DNA and protein more efficiently than HbA(0). Formation of carbonyl content, an index of oxidative stress, is higher by HbA(1c). Compared to HbA(0), HbA(1c) is more rapidly autooxidized. Besides these functional changes, glycation also causes structural modifications of hemoglobin. This is demonstrated by reduced alpha-helix content, more surface accessible hydrophobic tryptophan residues, increased thermolability and weaker heme-globin linkage in HbA(1c) than in its nonglycated analog. The glycation-induced structural modification of hemoglobin may be associated with its functional modification leading to oxidative stress in diabetic patients.
Sen
Subhrojit
S
Department of Biophysics, Molecular Biology and Genetics, University of Calcutta, 92 Acharyya Prafulla Chandra Road, Kolkata 700009, India.
Kar
Manoj
M
Roy
Anjana
A
Chakraborti
Abhay Sankar
AS
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002384:Catalysis; D004249:DNA Damage; D003920:Diabetes Mellitus / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry; D006442:Glycated Hemoglobin / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D018384:Oxidative Stress; D011487:Protein Conformation; D011489:Protein Denaturation; D013696:Temperature; D013997:Time Factors
D001786:Blood Glucose; D005609:Free Radicals; D006442:Glycated Hemoglobin; D006454:Hemoglobins; D006861:Hydrogen Peroxide; D007501:Iron