Effect of pyridoxamine on chemical
modification of proteins by carbonyls in diabetic rats: characterization
of a major product from the reaction of pyridoxamine and methylglyoxal.
Nagaraj RH, Sarkar P, Mally A,
Biemel KM, Lederer MO, Padayatti PS.
Center for Vision Research,
Department of Ophthalmology,
Case Western Reserve University and
University Hospitals of Cleveland, Wearn Building, Room 643, Cleveland,
OH 44106, USA. nhr@po.cwru.edu
Arch Biochem Biophys. 2002 Jun 1;402(1):110-9.
Abstract
Advanced glycation end products
(AGEs) from the Maillard reaction contribute to protein aging and the
pathogenesis of age- and diabetes-associated complications. The
alpha-dicarbonyl compound methylglyoxal (MG) is an important
intermediate in AGE synthesis. Recent studies suggest that pyridoxamine
inhibits formation of advanced glycation and lipoxidation products. We
wanted to determine if pyridoxamine could inhibit MG-mediated Maillard
reactions and thereby prevent AGE formation. When lens proteins were
incubated with MG at 37 degrees C, pH 7.4, we found that pyridoxamine
inhibits formation of methylglyoxal-derived AGEs concentration
dependently. Pyridoxamine reduces MG levels in red blood cells and
plasma and blocks formation of methylglyoxal-lysine dimer in plasma
proteins from diabetic rats and it prevents pentosidine (an AGE derived
from sugars) from forming in plasma proteins. Pyridoxamine also
decreases formation of protein carbonyls and
thiobarbituric-acid-reactive substances in plasma proteins from diabetic
rats. Pyridoxamine treatment did not restore erythrocyte glutathione
(which was reduced by almost half) in diabetic animals, but it enhanced
erythrocyte glyoxalase I activity. We isolated a major product of the
reaction between MG and pyridoxamine and identified it as
methylglyoxal-pyridoxamine dimer. Our studies show that pyridoxamine
reduces oxidative stress and AGE formation. We suspect that a direct
interaction of pyridoxamine with MG partly accounts for AGE inhibition.
