RHODOQUINONE IS SYNTHESIZED DE-NOVO BY FASCIOLA-HEPATICA

Most adult parasitic helminths have an anaerobic energy metabolism in which fumarate is reduced to succinate by fumarate reductase. Rhodoqui none (RQ) is an essential component of the electron transport associat ed with this fumarate reduction, whereas ubiquinone (UQ) is used in th e aerobic energy metabolism of parasites. Not known yet, however, is t he RQ and UQ composition during the entire life cycle nor the origin o f RQ in parasitic helminths. This report demonstrates the essential fu nction of RQ in anaerobic energy metabolism during the entire life cyc le of Fasciola hepatica, as the amount of RQ present reflected the imp ortance of fumarate reduction in various stages. We also studied the o rigin of RQ, as earlier studies on the protozoan Euglena gracilis sugg ested that RQ is synthesized from UQ. Therefore, in parasitic helminth s RQ might be synthesized by modification of UQ obtained from the host . However, we demonstrated that in F. hepatica adults RQ was not produ ced by modification of UQ obtained from the host but that RQ was synth esized 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 conver sion of UQ(9) into RQ(9) or into UQ(10), neither by intact adult fluke s nor by homogenates of F. hepatica adults and (iii) F. hepatica adult s used mevalonate as precursor for the synthesis of RQ. We also showed that the rate of quinone synthesis in F. hepatica adults was comparab le to that in the free-living nematode Caenorhabditis elegans. These r esults prompted the suggestion that RQ is synthesized via a pathway ne arly identical to that of UQ biosynthesis: possibly only the last reac tion differs.