Non enzymatic covalent modification by glycolysis end product converts hemoglobin into its oxidative stress potency state

P Esackimuthu; N T Saraswathi

doi:10.1016/j.bbrc.2020.11.072

Non enzymatic covalent modification by glycolysis end product converts hemoglobin into its oxidative stress potency state

Biochem Biophys Res Commun. 2021 Jan 1:534:387-394. doi: 10.1016/j.bbrc.2020.11.072. Epub 2020 Nov 28.

Authors

P Esackimuthu¹, N T Saraswathi²

Affiliations

¹ Molecular Biophysics Lab, School of Chemical and Biotechnology, SASTRA Deemed To Be University, Thanjavur, 613401, Tamilnadu, India.
² Molecular Biophysics Lab, School of Chemical and Biotechnology, SASTRA Deemed To Be University, Thanjavur, 613401, Tamilnadu, India. Electronic address: saras@scbt.sastra.edu.

PMID: 33261885
DOI: 10.1016/j.bbrc.2020.11.072

Abstract

The effect of glycation by Pyruvic acid (PA) on the early and advanced conformational changes in Hemoglobin (Hb) was studied. Multi Spectroscopic measurement revealed that Hb undergoes structural conformational changes and unbound heme upon incubation with PA. These covalent modifications were followed by the reduction of heme centre and these reduction processes initiates its peroxidase-like activity. An extended PA glycation resulted in the appearance of advanced glycation end products fluorescence, with notable changes in compositions of secondary structure. The amyloidogenic state was confirmed by SEM, fluorescence microscope observation. This study reveals an insight to the role of pyruvic acid which increases the oxidative stress due to the heme reduction and diabetic complication.

Keywords: Aggregation; Amyloidogenesis; Carboxymethyl lysine; EPR; Glycation; Oxidative stress; Secondary structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloidogenic Proteins / chemistry
Amyloidogenic Proteins / metabolism
Arginine / chemistry
Coloring Agents
Congo Red
Electron Spin Resonance Spectroscopy
Glycated Hemoglobin / chemistry*
Glycated Hemoglobin / metabolism*
Glycated Hemoglobin / ultrastructure
Glycation End Products, Advanced / chemistry
Glycation End Products, Advanced / metabolism
Glycolysis
Glycosylation
Heme / chemistry
Hemoglobins / chemistry*
Hemoglobins / metabolism*
Hemoglobins / ultrastructure
Humans
In Vitro Techniques
Lysine / chemistry
Microscopy, Electron, Scanning
Oxidation-Reduction
Oxidative Stress
Protein Aggregates
Protein Conformation
Protein Structure, Secondary
Pyruvic Acid / chemistry
Spectrometry, Fluorescence
Spectrophotometry, Ultraviolet

Substances

Amyloidogenic Proteins
Coloring Agents
Glycated Hemoglobin A
Glycation End Products, Advanced
Hemoglobins
Protein Aggregates
Congo Red
Heme
Pyruvic Acid
Arginine
Lysine