Kawabata T, Packer L
Department of Molecular & Cell Biology, University of California, Berkeley 94720-3200.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):99-104. doi: 10.1006/bbrc.1994.2154.
Protein glycation may play a role in the pathogenesis of diabetic complications. alpha-Lipoate (1,2-dithiolane-3-pentanoate) has been reported to prevent glycation and structural modification of bovine serum albumin (BSA). To elucidate the protective mechanism, we tested the effects of enantiomerism, thiol moiety and hydrophobicity of alpha-lipoate on glycation of BSA and low density lipoprotein (LDL). When BSA (1 mM) was incubated with 500 mM glucose in the presence of alpha-lipoate homologues or dihydrolipoate (6,8-dimercaptooctanoate, DHLA) at 37 degrees C for 72 h, both alpha-lipoate (racemic, R- and S-forms) and DHLA inhibited BSA glycation similarly, but tetranorlipoate (1,2-dithiolane-3-carboxylate) did not. However, under similar conditions, alpha-lipoate did not inhibit LDL glycation. Scatchard plot analysis demonstrated that 6 mol of alpha-lipoate bind to 1 mol of BSA with a formation constant of 8.7 x 10(4) M-1. Therefore, we concluded that alpha-lipoate protects BSA glycation by hydrophobic binding near the glycation sites of BSA.
蛋白质糖基化可能在糖尿病并发症的发病机制中起作用。据报道，α-硫辛酸（1,2-二硫戊环-3-戊酸）可防止牛血清白蛋白（BSA）的糖基化和结构修饰。为了阐明其保护机制，我们测试了α-硫辛酸的对映体、硫醇部分和疏水性对BSA和低密度脂蛋白（LDL）糖基化的影响。当在37℃下将1 mM的BSA与500 mM葡萄糖在α-硫辛酸同系物或二氢硫辛酸（6,8-二巯基辛酸，DHLA）存在下孵育72小时时，α-硫辛酸（外消旋体、R-和S-形式）和DHLA对BSA糖基化的抑制作用相似，但四去甲硫辛酸（1,2-二硫戊环-3-羧酸盐）则无此作用。然而，在类似条件下，α-硫辛酸并不抑制LDL的糖基化。Scatchard图分析表明，6摩尔α-硫辛酸与1摩尔BSA结合，形成常数为8.7×10⁴ M⁻¹。因此，我们得出结论，α-硫辛酸通过在BSA糖基化位点附近的疏水结合来保护BSA的糖基化。
