Kearley M L, Patel A, Chien J, Tuma D J
Department of Chemistry, Creighton University, Omaha, Nebraska 68178, USA.
Chem Res Toxicol. 1999 Jan;12(1):100-5. doi: 10.1021/tx980132u.
It has been shown that malondialdehyde (MDA) and acetaldehyde react with proteins via the epsilon-amino group of a lysine residue to yield hybrid MDA-acetaldehyde (MAA)-protein adducts. The structure of one MAA adduct has been confirmed to be 4-methyl-1, 4-dihydropyridine-3,5-dicarbaldehyde (3). In this study, 13C NMR spectroscopy was used to identify the structure of a second MAA adduct as 2-formyl-3-(alkylamino)butanal (4). Isotopically labeled [1-13C]acetaldehyde was reacted with MDA and the protein, bovine serum albumin, under a variety of conditions, and the reactions were monitored at various time intervals by 13C NMR. In each experiment, new signals grew in at 50 and 22 ppm. By comparison to model compounds, the signals at 50 ppm correspond to a 2-formyl-3-(alkylamino)butanal adduct and the signals at 22 ppm correspond to the known 1,4-dihydropyridine-3,5-dicarbaldehyde adduct. Similar results were found when the BSA was replaced with polylysine. Overall, it appears that MAA-protein adducts are composed of two major products, 3 and 4.
研究表明，丙二醛（MDA）和乙醛通过赖氨酸残基的ε-氨基与蛋白质发生反应，生成混合的丙二醛-乙醛（MAA）-蛋白质加合物。已证实一种MAA加合物的结构为4-甲基-1,4-二氢吡啶-3,5-二甲醛（3）。在本研究中，利用13C核磁共振光谱法确定了另一种MAA加合物的结构为2-甲酰基-3-（烷基氨基）丁醛（4）。将同位素标记的[1-13C]乙醛在多种条件下与MDA及蛋白质牛血清白蛋白反应，并通过13C核磁共振在不同时间间隔监测反应。在每个实验中，新信号在50 ppm和22 ppm处出现。通过与模型化合物比较，50 ppm处的信号对应于2-甲酰基-3-（烷基氨基）丁醛加合物，22 ppm处的信号对应于已知的1,4-二氢吡啶-3,5-二甲醛加合物。当用聚赖氨酸替代牛血清白蛋白时，得到了类似的结果。总体而言，MAA-蛋白质加合物似乎由两种主要产物3和4组成。
