Shigeta Tomoaki, Sasamoto Kazumi, Yamamoto Tetsuro
Bloom Technology Corporation, 3-14-3 Minamikumamoto, Kumamoto 860-0812, Japan.
Heliyon. 2020 Nov 8;6(11):e05337. doi: 10.1016/j.heliyon.2020.e05337. eCollection 2020 Nov.
Glycation of amino or guanidino groups of proteins with glucose and glucose-derived reactive aldehydes, such as α-hydroxyaldehydes, leads to accumulation of advanced glycation end-products (AGEs) in the body, resulting in diabetic complications and age-related pathology. Although molecular structures of glycolaldehyde- and glyceraldehyde-derived AGEs have been described in previous studies, little is known about lactaldehyde-derived AGEs of α-hydroxyaldehydes. Here, we report a novel crosslinked type of AGE, named as lactaldehyde-derived lysine dimer (LAK2), which is produced due to non-enzymatic glycation of -acetyl--lysine with lactaldehyde under physiological conditions. We have identified the molecular structure of LAK2 by extensive mass spectrometry and nuclear magnetic resonance analyses. Furthermore, we propose a reaction pathway to produce LAK2, in which it is formed through an intermediate common with the recently reported lactaldehyde-derived pyridinium-type lysine adduct (LAPL). Since lactaldehyde is known to be produced from L-threonine in a myeloperoxidase (MPO)-mediated reaction at sites of inflammation, LAK2 has the potential to be an oxidative stress marker of MPO-mediated reactions induced in inflammation.
蛋白质的氨基或胍基与葡萄糖及葡萄糖衍生的活性醛（如α-羟基醛）发生糖基化反应，会导致体内晚期糖基化终产物（AGEs）的积累，进而引发糖尿病并发症和与年龄相关的病理变化。尽管先前的研究已经描述了乙醇醛和甘油醛衍生的AGEs的分子结构，但对于α-羟基醛中乳醛衍生的AGEs却知之甚少。在此，我们报告一种新型的交联型AGE，命名为乳醛衍生的赖氨酸二聚体（LAK2），它是在生理条件下，α-乙酰-赖氨酸与乳醛发生非酶糖基化反应产生的。我们通过广泛的质谱分析和核磁共振分析确定了LAK2的分子结构。此外，我们提出了一条产生LAK2的反应途径，即它是通过与最近报道的乳醛衍生的吡啶型赖氨酸加合物（LAPL）共有的中间体形成的。由于已知乳醛是在炎症部位由髓过氧化物酶（MPO）介导的反应中由L-苏氨酸产生的，因此LAK2有可能成为炎症中MPO介导反应的氧化应激标志物。
