Nihei Coichi, Fukai Yoshihisa, Kita Kiyoshi
Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Biochim Biophys Acta. 2002 Jul 18;1587(2-3):234-9. doi: 10.1016/s0925-4439(02)00086-8.
Parasites have developed a variety of physiological functions necessary for their survival within the specialized environment of the host. Using metabolic systems that are very different from those of the host, they can adapt to low oxygen tension present within the host animals. Most parasites do not use the oxygen available within the host to generate ATP, but rather employ systems anaerobic metabolic pathways. The enzymes in these parasite-specific pathways are potential targets for chemotherapy.Cyanide-insensitive trypanosome alternative oxidase (TAO) is the terminal oxidase of the respiratory chain of long slender bloodstream forms of the African trypanosome, which causes sleeping sickness in human and nagana in cattle. TAO has been targeted for the development of anti-trypanosomal drugs because it does not exist in the host. Recently, we found the most potent inhibitor of TAO to date, ascofuranone, a compound isolated from the phytopathogenic fungus, Ascochyta visiae.
寄生虫已经发展出多种生理功能，这些功能对于它们在宿主的特殊环境中生存是必需的。它们利用与宿主截然不同的代谢系统，能够适应宿主动物体内存在的低氧张力。大多数寄生虫并不利用宿主体内可用的氧气来产生三磷酸腺苷（ATP），而是采用无氧代谢途径系统。这些寄生虫特异性途径中的酶是化疗的潜在靶点。对氰化物不敏感的锥虫替代氧化酶（TAO）是非洲锥虫长细血流形式呼吸链的末端氧化酶，这种锥虫会导致人类昏睡病和牛的那加那病。由于宿主中不存在TAO，它已成为抗锥虫药物开发的靶点。最近，我们发现了迄今为止最有效的TAO抑制剂——曲霉呋喃酮，一种从植物致病真菌葡萄座腔菌中分离出的化合物。
