Characterizing the advanced glycation endproducts formation of proteins and nucleotides by methylglyoxal and glyoxal

Praveen Kumar Pampati, University of Rhode Island

Abstract

Advanced glycation endproducts (AGEs) are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and nucleic acids. The initial product of this reaction is called a Schiff base, which rearranges itself into an Amadori or glycation product which can further rearrange to AGEs. The reaction is called Maillard reaction and is the basis for all protein glycation studies. AGEs accumulate in tissues and associate with the pathology of various diseases like Diabetes, Alzheimer's disease, renal failure, aging, etc. ^ Methylglyoxal, 3-Deoxyglucosone and glyoxal (oxoaldehydes or α-dicarbonyls) have recently been proposed to be formed from all stages of the glycation process by degradation of glucose or Schiff's bases in early glycation, or from Amadori products such as fructosamine in the intermediate stages of glycation. A model system was designed in this study to investigate the advanced glycation endproduct formation by human immunoglobulins and cyclic nucleotides with oxoaldehydes and other reducing sugars.^ The objective of this thesis was to study the nonenzymatic glycation of human immunoglobulin G and cyclic nucleotides in vitro because modification of either of these could affect the immunological and physiological responses. The effect of various reducing sugars on the secondary structure of immunoglobulin G is analyzed by utilizing a combination of analytical techniques such as Circular dichroism, MALDI-TOF/MS and UV-Visible and fluorescence spectroscopy. The study demonstrated that the methylglyoxal is highly reactive and effective in the formation of glycated immunoglobulin G.^ The second study is to monitor the in vitro AGE formation for studying the effect of different reducing sugars on cyclic nucleotides in comparison with acyclic nucleotides. This study is carried out by utilizing a combination of analytical techniques such as UV-Fluorescence spectroscopy and HPLC. This study demonstrated that the AGE formation of cyclic nucleotides by different reducing sugars was more extensive compared to acyclic nucleotides and cGMP is highly reactive in forming the glycation adducts of all the cyclic nucleotides. ^

Subject Area

Chemistry, Analytical|Chemistry, Biochemistry

Recommended Citation

Praveen Kumar Pampati, "Characterizing the advanced glycation endproducts formation of proteins and nucleotides by methylglyoxal and glyoxal" (2010). Dissertations and Master's Theses (Campus Access). Paper AAI3451842.
http://digitalcommons.uri.edu/dissertations/AAI3451842

Share

COinS