Schleicher E, Wieland O H
Biochim Biophys Acta. 1986 Oct 29;884(1):199-205. doi: 10.1016/0304-4165(86)90244-8.
Glycation of proteins, a common postribosomal modification, proceeds via Amadori rearrangement to yield a stable ketoamine linkage of glucose with the protein. Kinetic analysis of the reaction shows that the amount of glycation at steady state is proportional to the glucose concentration, to protein half-life and to the rate of glycation. Thus, when the rate of glycation is determined in vitro and the extent of glycation of a given protein isolated from euglycemic subjects is measured, the half-life may be calculated. As the in vivo situation may not be simulated accurately in vitro, the calculated values may be considered as approximation. When the calculated values were compared with values reported in the literature fairly good agreement was found except for hemoglobin. Studies on stability of glycated albumin show that ketoamine decreases by about 20% when incubated under physiological conditions for 20 days. The method described by us is especially valuable when turnover of proteins in normal and pathophysiological states are compared. The half-life of plasma low-density lipoprotein is longer in patients with hypothyroidism or a high plasma low-density lipoprotein level than in normal subjects. Extending our studies to tissue proteins we did not find a significant increase in half-life of tendon collagen with age. Basement membrane collagen turnover is faster in diabetic patients in bad metabolic control. Thus, the procedure using fructosylamine as endogenous label of protein offers a method of great potential to study the turnover of human body proteins.
蛋白质糖基化是一种常见的核糖体后修饰，通过阿马多里重排进行，产生葡萄糖与蛋白质的稳定酮胺键。该反应的动力学分析表明，稳态下的糖基化量与葡萄糖浓度、蛋白质半衰期和糖基化速率成正比。因此，当在体外测定糖基化速率并测量从血糖正常的受试者中分离出的给定蛋白质的糖基化程度时，就可以计算出半衰期。由于体外可能无法准确模拟体内情况，因此计算值可视为近似值。将计算值与文献报道的值进行比较时，除血红蛋白外，发现吻合度相当好。对糖化白蛋白稳定性的研究表明，在生理条件下孵育20天时，酮胺减少约20%。当比较正常和病理生理状态下蛋白质的周转率时，我们描述的方法特别有价值。甲状腺功能减退症患者或血浆低密度脂蛋白水平高的患者，血浆低密度脂蛋白的半衰期比正常受试者长。将我们的研究扩展到组织蛋白时，我们没有发现肌腱胶原蛋白的半衰期随年龄显著增加。代谢控制不良的糖尿病患者基底膜胶原蛋白的周转率更快。因此，使用果糖胺作为蛋白质内源性标记的方法为研究人体蛋白质的周转率提供了一种极具潜力的方法。
