Thornalley P J, Argirova M, Ahmed N, Mann V M, Argirov O, Dawnay A
Department of Biological Sciences, University of Essex, Essex, England, United Kingdom. Kingdom.
Kidney Int. 2000 Nov;58(5):2228-34. doi: 10.1111/j.1523-1755.2000.00398.x.
Advanced glycation end products (AGEs) are a novel class of uremic toxins. In plasma, they are present in proteins and also in low molecular mass peptides. AGE-modified peptides are thought to bind and modify plasma proteins. Monitoring of the consequent increase in molecular mass of serum albumin may be used in surveillance of the clinical management of uremia.
We investigated molecular mass changes of human serum albumin (HSA) glycated by glucose and methylglyoxal in vitro and of subjects with moderate renal impairment, end-stage renal disease (ESRD), ESRD on hemodialysis, and normal healthy controls by matrix-assisted laser desorption ionization mass spectrometry.
Fatty acid-free HSA had a molecular mass of 66,446 +/- 114 D. Mean (+/-SD) molecular mass increases were HSA minimally glycated by glucose 399 +/- 88 D (N = 5, P < 0.001), HSA highly glycated by glucose 6780 +/- 122 D (N = 5, P < 0.001), HSA minimally glycated by methylglyoxal 73 +/- 121 D (N = 5, P > 0.05), and HSA without fatty acid removal 535 +/- 90 D (N = 5, P < 0.001). For HSA of human subjects, mean (+/- SD) molecular mass increases were normal healthy controls 243 +/- 97 D (N = 5), moderate renal impairment 350 +/- 83 D (P > 0.05 with respect to controls, N = 5), ESRD 498 +/- 128 (P < 0.02 with respect to controls, N = 3), and ESRD on hemodialysis 438 +/- 85 D (P < 0.02 with respect to controls, N = 5). The mean molecular mass of albumin of all groups was increased significantly with respect to that of fatty acid free albumin (P < 0.001).
Only ESRD was associated with a significant increase in the molecular mass of HSA in vivo. Since this mass increase was very low and much lower than reported for AGE-modified peptides, it may reflect AGE formation on HSA by alpha-oxoaldehydes that accumulate in uremia, rather than modification of albumin by AGE-modified peptides. The molecular mass of HSA in vivo was indicative of a minimal and not a high extent of glycation.
晚期糖基化终末产物（AGEs）是一类新型尿毒症毒素。在血浆中，它们存在于蛋白质以及低分子量肽中。AGE修饰的肽被认为会结合并修饰血浆蛋白。监测血清白蛋白分子量的相应增加可用于监测尿毒症的临床管理。
我们通过基质辅助激光解吸电离质谱法，研究了体外被葡萄糖和甲基乙二醛糖基化的人血清白蛋白（HSA）以及中度肾功能损害患者、终末期肾病（ESRD）患者、接受血液透析的ESRD患者和正常健康对照者的HSA分子量变化。
无脂肪酸的HSA分子量为66,446±114 D。平均（±标准差）分子量增加情况为：葡萄糖轻度糖基化的HSA增加399±88 D（N = 5，P < 0.001），葡萄糖高度糖基化的HSA增加6780±122 D（N = 5，P < 0.001），甲基乙二醛轻度糖基化的HSA增加73±121 D（N = 5，P > 0.05），未去除脂肪酸的HSA增加535±90 D（N = 5，P < 0.001）。对于人类受试者的HSA，平均（±标准差）分子量增加情况为：正常健康对照者增加243±97 D（N = 5），中度肾功能损害者增加350±83 D（相对于对照，P > 0.05，N = 5），ESRD患者增加498±128 D（相对于对照，P < 0.02，N = 3），接受血液透析的ESRD患者增加438±85 D（相对于对照，P < 0.02，N = 5）。所有组白蛋白的平均分子量相对于无脂肪酸白蛋白均显著增加（P < 0.001）。
只有ESRD与体内HSA分子量的显著增加相关。由于这种分子量增加非常低，且远低于报道的AGE修饰肽的增加量，它可能反映了尿毒症中积累的α-氧代醛在HSA上形成AGE，而非AGE修饰肽对白蛋白的修饰。体内HSA的分子量表明糖基化程度很低而非很高。
