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醌类对醛糖还原酶的抑制作用:降血糖作用。

Inhibition effects of quinones on aldose reductase: Antidiabetic properties.

机构信息

Department of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey; Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, 75700, Ardahan, Turkey.

Department of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey; Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, 75700, Ardahan, Turkey.

出版信息

Environ Toxicol Pharmacol. 2019 Aug;70:103195. doi: 10.1016/j.etap.2019.103195. Epub 2019 May 13.

Abstract

Diabetes mellitus is a chronic metabolic disease characterized by abnormal glucose metabolism. Aldose reductase (AR) is the first enzyme in the polyol pathway and converts glucose to sorbitol. It plays a vital role as a glucose reducing agent and is involved in the pathophysiology of diabetic complications. In this study, we purified AR from sheep kidney with a specific activity of 2.00 EU/mg protein and 133.33- fold purification After the purification of the AR enzyme, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed and the molecular weight of the enzyme was found approximately as 38 kDa. The inhibition effects of eight quinones were studied against AR. The quinones were potent inhibitors of AR with K values in the range of 0.07-20.04 μM. Anthraquinone showed the best potential inhibitory effects against AR. All compounds exhibited noncompetitive inhibition against AR. These compounds may be selective inhibitors of this enzyme. AR inhibition is an essential strategy for the attenuation and prevention of diabetic complications.

摘要

糖尿病是一种以葡萄糖代谢异常为特征的慢性代谢性疾病。醛糖还原酶(AR)是多元醇途径中的第一个酶,可将葡萄糖转化为山梨醇。它作为一种葡萄糖还原剂发挥着重要作用,并且参与糖尿病并发症的病理生理学过程。在这项研究中,我们从绵羊肾脏中纯化出 AR,其比活为 2.00 EU/mg 蛋白,纯化倍数为 133.33 倍。在对 AR 酶进行纯化后,进行了十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE),发现该酶的分子量约为 38 kDa。研究了八种醌类化合物对 AR 的抑制作用。这些醌类化合物对 AR 具有很强的抑制作用,K 值在 0.07-20.04 μM 范围内。蒽醌对 AR 表现出最好的潜在抑制作用。所有化合物均对 AR 表现出非竞争性抑制。这些化合物可能是该酶的选择性抑制剂。抑制 AR 是减轻和预防糖尿病并发症的重要策略。

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