Lo T W, Selwood T, Thornalley P J
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Biochem Pharmacol. 1994 Nov 16;48(10):1865-70. doi: 10.1016/0006-2952(94)90584-3.
Increased formation of methylglyoxal in clinical diabetes mellitus and metabolism by the glyoxalase system has been linked to the development of clinical complications of diabetes: retinopathy, neuropathy and nephropathy. Aminoguanidine has been proposed as a prophylactic agent for preventive therapy of diabetic complications. Methylglyoxal reacted with aminoguanidine under physiological conditions to form two isomeric triazines, 3-amino-5-methyl-1,2,4-triazine and 3-amino-6-methyl-1,2,4-triazine. The mean second order rate constant for the reaction of methylglyoxal with aminoguanidine, kMG.AG = 0.39 +/- 0.06 M-1 sec-1 at pH 7.4 and 37 degrees. Under these conditions, no methylglyoxal bisguanylhydrazone was detected. Aminoguanidine prevented the irreversible modification of human plasma protein by a physiological concentration of methylglyoxal (1 microM); the median inhibitory concentration IC50 value of aminoguanidine was 203 +/- 16 microM (N = 28). The scavenging of methylglyoxal by aminoguanidine may contribute to the beneficial effects of aminoguanidine in the prevention of vascular pathogenesis in diabetes.
临床糖尿病中甲基乙二醛生成增加以及乙二醛酶系统对其代谢与糖尿病临床并发症（视网膜病变、神经病变和肾病）的发生有关。氨基胍已被提议作为预防糖尿病并发症的预防性治疗药物。甲基乙二醛在生理条件下与氨基胍反应形成两种异构三嗪，即3-氨基-5-甲基-1,2,4-三嗪和3-氨基-6-甲基-1,2,4-三嗪。甲基乙二醛与氨基胍反应的平均二级速率常数，在pH 7.4和37摄氏度时，kMG.AG = 0.39 +/- 0.06 M-1秒-1。在这些条件下，未检测到甲基乙二醛双脒腙。氨基胍可防止生理浓度的甲基乙二醛（1 microM）对人血浆蛋白进行不可逆修饰；氨基胍的半数抑制浓度IC50值为203 +/- 16 microM（N = 28）。氨基胍对甲基乙二醛的清除作用可能有助于其在预防糖尿病血管病变中的有益作用。
