State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
Int J Biol Macromol. 2018 Jun;112:405-412. doi: 10.1016/j.ijbiomac.2018.01.190. Epub 2018 Jan 31.
Quercetin, one of the most abundant flavonoid in the daily diet, was found to reversibly inhibit the generation of uric acid and superoxide radicals (O)catalyzed by xanthine oxidase (XOD) in a mixed-type manner with IC values of (2.74±0.04)×10 and (2.90±0.03)×10molL, respectively, and the inhibition of quercetin on O generation may be ascribed to the reduced form of XOD by a ping-pong mechanism. XOD had one high affinity binding site for quercetin with a binding constant of 4.28×10Lmol at 298K, and the binding process was predominately driven by van der Waals forces and hydrogen bonds on account of the negative enthalpy and entropy changes. Moreover, molecular docking confirmed that the binding site for quercetin located in the isoalloxazine ring of the flavin adenine dinucleotide (FAD) domain of XOD, then the diffusion of O out of the FAD site was blocked in favor of another electron transferred from FADH to O to form hydrogen peroxide (HO). This study may clarify the role of quercetin on inhibiting XOD catalysis and provide a potential nutritional supplement for preventing gout and peroxidative damage.
槲皮素是日常饮食中最丰富的类黄酮之一，被发现以混合方式可逆地抑制黄嘌呤氧化酶 (XOD) 催化的尿酸和超氧自由基 (O) 的生成，IC 值分别为 (2.74±0.04)×10 和 (2.90±0.03)×10mol/L，槲皮素对 O 生成的抑制作用可能归因于 XOD 的还原形式通过乒乓机制。XOD 对槲皮素有一个高亲和力结合位点，在 298K 时的结合常数为 4.28×10Lmol，结合过程主要由范德华力和氢键驱动，由于焓变和熵变均为负值。此外，分子对接证实，槲皮素的结合位点位于 XOD 的黄素腺嘌呤二核苷酸 (FAD) 结构域的异咯嗪环中，然后 O 从 FAD 位点扩散出来受阻，有利于另一个电子从 FADH 转移到 O 形成过氧化氢 (HO)。本研究可能阐明了槲皮素抑制 XOD 催化的作用，并为预防痛风和过氧化损伤提供了一种潜在的营养补充剂。
