Van Hellemond J J, Luijten M, Flesch F M, Gaasenbeek C P, Tielens A G
Laboratory of Veterinary Biochemistry, Utrecht University, The Netherlands.
Mol Biochem Parasitol. 1996 Nov 25;82(2):217-26. doi: 10.1016/0166-6851(96)02738-7.
Most adult parasitic helminths have an anaerobic energy metabolism in which fumarate is reduced to succinate by fumarate reductase. Rhodoquinone (RQ) is an essential component of the electron transport associated with this fumarate reduction, whereas ubiquinone (UQ) is used in the aerobic energy metabolism of parasites. Not known yet, however, is the RQ and UQ composition during the entire life cycle nor the origin of RQ in parasitic helminths. This report demonstrates the essential function of RQ in anaerobic energy metabolism during the entire life cycle of Fasciola hepatica, as the amount of RQ present reflected the importance of fumarate reduction in various stages. We also studied the origin of RQ, as earlier studies on the protozoan Euglena gracilis suggested that RQ is synthesized from UQ. Therefore, in parasitic helminths RQ might be synthesized by modification of UQ obtained from the host. However, we demonstrated that in F. hepatica adults RQ was not produced by modification of UQ obtained from the host but that RQ was synthesized de novo, as (i) the chain-length of the quinones of F. hepatica adults was not related to the chain length of the quinone of the host, (ii) despite many attempts we could never detect any in vitro conversion of UQ9 into RQ9 or into UQ10, neither by intact adult flukes nor by homogenates of F. hepatica adults and (iii) F. hepatica adults used mevalonate as precursor for the synthesis of RQ. We also showed that the rate of quinone synthesis in F. hepatica adults was comparable to that in the free-living nematode Caenorhabditis elegans. These results prompted the suggestion that RQ is synthesized via a pathway nearly identical to that of UQ biosynthesis: possibly only the last reaction differs.
大多数成年寄生蠕虫具有无氧能量代谢,其中富马酸酯通过富马酸酯还原酶还原为琥珀酸酯。玫红醌(RQ)是与这种富马酸酯还原相关的电子传递的重要组成部分,而泛醌(UQ)则用于寄生虫的有氧能量代谢。然而,目前尚不清楚在整个生命周期中RQ和UQ的组成情况,也不清楚寄生蠕虫中RQ的来源。本报告证明了RQ在肝片吸虫整个生命周期的无氧能量代谢中的重要作用,因为RQ的含量反映了富马酸酯还原在各个阶段的重要性。我们还研究了RQ的来源,因为早期对原生动物纤细裸藻的研究表明RQ是由UQ合成的。因此,在寄生蠕虫中,RQ可能是通过修饰从宿主获得的UQ而合成的。然而,我们证明在肝片吸虫成虫中,RQ不是通过修饰从宿主获得的UQ产生的,而是从头合成的,原因如下:(i)肝片吸虫成虫醌的链长与宿主醌的链长无关;(ii)尽管进行了多次尝试,我们从未检测到UQ9在体外转化为RQ9或UQ10,无论是完整的成虫还是肝片吸虫成虫的匀浆都无法检测到;(iii)肝片吸虫成虫使用甲羟戊酸作为RQ合成的前体。我们还表明,肝片吸虫成虫中醌的合成速率与自由生活的线虫秀丽隐杆线虫相当。这些结果提示,RQ可能通过与UQ生物合成几乎相同的途径合成:可能只是最后一步反应不同。