Submitted on August 5, 2005
Revised on February 7, 2006
Accepted on February 8, 2006
Aminophospholipid glycation and its inhibitor screening system: A new role of pyridoxal 5'-phosphate and pyridoxal as lipid glycation inhibitor
Ohki Higuchi, Kiyotaka Nakagawa, Tsuyoshi Tsuzuki, Toshihide Suzuki, Shinichi Oikawa, and Teruo Miyazawa
Tohoku University, Sendai
Corresponding Author: miyazawa{at}biochem.tohoku.ac.jp
Peroxidized phospolipid-mediated cytotoxity involves in the pathophysiology of diseases (i.e., an abnormal increase of phosphatidylcholine hydroperoxide, PCOOH, found in plasma of type 2 diabetic patients). The PCOOH accumulation may relate to Amadori-glycated phosphatidylethanolamine (deoxy-D-fructosyl PE, namely Amadori-PE), since Amadori-PE causes oxidative stress. However, lipid glycation inhibitor has not been discovered yet due to lack of a lipid glycation model study useful for inhibitor screening. Consequently, we optimized and developed a lipid glycation model considering various reaction conditions (glucose concentration, temperature, buffer type and pH) between phosphatidylethanolamine (PE) and glucose. Using the developed model, various protein glycation inhibitors (aminoguanidine, pyridoxamine, aspirin and carnosine), antioxidants (ascorbic acid,
-tocopherol, quercetin and rutin) and other food compounds (L-lysine, L-cysteine, pyridoxine, pyridoxal and pyridoxal 5'-phosphate) were evaluated for their anti-glycative property. As results, pyridoxal 5'-phosphate and pyridoxal (vitamin B6 derivatives) were the most effective anti-glycative compounds. These pyridoxals could easily be condensed with PE before glucose/PE reaction occurred. Since we found that PE-pyridoxal 5'-phosphate adduct was detectable in human red blood cells and that elevated plasma Amadori-PE concentration in streptozotocin-induced diabetic rats was decreased by dietary supplementation of pyridoxal 5'-phosphate, it is likely that pyridoxal 5'-phosphate acts as lipid glycation inhibitor in vivo, which possibly contributes to diabetes prevention.