Ren Xiaoli, Luo Fen, Li Xixi, Yi Sha, Yang Bing, Jiang Zhiyong
Food and Drug Teaching and Research Department, School of Environment and Quality Testing, Chongqing Chemical Industry Vocational College, Chongqing 401228, China.
Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Sheng Wu Gong Cheng Xue Bao. 2020 Dec 25;36(12):2732-2740. doi: 10.13345/j.cjb.200166.
Dihydroorotate dehydrogenase is a flavin-dependent mitochondrial enzyme to catalyze the fourth step of the de novo synthesis of pyrimidine and to oxidize dihydroorotate to orotate. By selectively inhibiting dihydroorotate dehydrogenase, thereby inhibiting pyrimidine synthesis, the enzyme has been developed for the treatment of cancer, autoimmune diseases, bacterial or viral infections, parasitic diseases and so on. The development of inhibitory drugs requires a detailed understanding of the structural characteristics and catalytic cycle mechanism of dihydroorotate dehydrogenase. Therefore, this paper reviews these two aspects, and indicates perspectives of these inhibitors in clinical application.
二氢乳清酸脱氢酶是一种依赖黄素的线粒体酶,催化嘧啶从头合成的第四步反应,将二氢乳清酸氧化为乳清酸。通过选择性抑制二氢乳清酸脱氢酶,从而抑制嘧啶合成,该酶已被开发用于治疗癌症、自身免疫性疾病、细菌或病毒感染、寄生虫病等。抑制性药物的开发需要详细了解二氢乳清酸脱氢酶的结构特征和催化循环机制。因此,本文综述了这两个方面,并指出了这些抑制剂在临床应用中的前景。