Hamada Y, Araki N, Koh N, Nakamura J, Horiuchi S, Hotta N
Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):539-43. doi: 10.1006/bbrc.1996.1695.
To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.
为阐明糖酵解途径和多元醇途径的中间代谢产物在生理条件下非酶糖基化中的作用，我们将牛血清白蛋白与微摩尔浓度范围内的这两条途径的中间代谢产物以及20 mmol/L葡萄糖一起孵育，并观察晚期糖基化终产物（AGEs）的形成。我们发现磷酸丙糖、甘油醛以及一种新型的与多元醇途径相关的代谢产物3-磷酸果糖及其分解产物3-脱氧葡萄糖酮是极强的糖化剂，在与白蛋白孵育时，接近生理浓度时，早在24小时就会产生大量AGEs，而20 mmol/L葡萄糖在孵育两周后仅产生痕量AGEs。这些结果以及先前关于糖尿病状态下中间代谢产物水平升高的证据可能表明，尽管中间代谢产物的浓度与葡萄糖相比要低得多，但中间代谢产物而非葡萄糖才是导致糖尿病组织中糖基化增强的原因。
