Mitochondrial Hydrogen Peroxide Formation and the Fumarate Reductase of Hymenolepis diminuta

Abstract

The catalysis of hydrogen peroxide accumulation by the mitochondrial, membrane-associated NADH oxidase and less active succinoxidase of adult Hymenolepis diminuta was confirmed. NADH-dependent peroxide formation by isolated mitochondrial membranes occurred at about half the coincident rates of NADH and oxygen utilization, whereas succinate-dependent peroxide formation accounted for approximately 40% of the oxygen consumed. These findings, coupled with evaluations of the oxidases, indicated that both systems use in common 2 mechanisms for oxygen reduction, 1 of which is peroxide-forming. Neither system was sensitive to cyanide, azide, or antimycin A. Rotenone inhibition of NADH oxidation resulted in equivalent decreases in oxygen consumption by the peroxide-forming and nonperoxide-forming mechanisms. In contrast, malonate inhibition occurred via disruption of the peroxide-forming mechanism. Fumarate stimulated membrane-catalyzed NADH oxidation, despite aerobic conditions, and this fumarate reductase was rotenone-sensitive. NADH- or succinate-dependent peroxide formation virtually was abolished and oxygen consumption was minimal in the presence of fumarate. Malonate also inhibited fumarate-dependent NADH oxidation and succinate-dependent peroxide formation/oxygen consumption. Collectively, these findings clearly indicate that NADH- or succinate-dependent hydrogen peroxide accumulation involves the malonate-sensitive fumarate reductase, in the absence of fumarate. A model of the H. diminuta electron transport system is presented.

Metabolic transition in the development of Hymenolepis diminuta (Cestoda)

“…Signi®cantly, under aerobic conditions, adult H. diminuta mitochondria not only catalyze enhanced NADH utilization in the presence of fumarate but also preferentially reduce fumarate rather than oxygen (Fioravanti and Reisig 1990). With H. diminuta cysticercoids, NADH disappearance observed in the presence of fumarate did not dier markedly from that seen in its absence.…”

“…Aside from the fumarate reductase, adult H. diminuta mitochondria exhibit a less active, peroxide-forming, rotenone-sensitive NADH oxidase (Fioravanti 1981;Fioravanti and Reisig 1990). Signi®cantly, under aerobic conditions, adult H. diminuta mitochondria not only catalyze enhanced NADH utilization in the presence of fumarate but also preferentially reduce fumarate rather than oxygen (Fioravanti and Reisig 1990).…”

“…For the predominant lactate former Schistosoma mansoni, PEPCK/PK is much less than unity, whereas for H. diminuta it exceeds . A succinate-forming ability is also suggested by the fumarate reductase/NADH oxidase activity ratio (FR/NO) of adult H. diminuta mitochondria, a ratio that approaches 5.0 (Fioravanti and Reisig 1990;Fioravanti et al 1992). In the present study the cysticercoid PEPCK/PK was about 0.6 and the FR/ NO was, at best, 1.3.…”

Transhydrogenase and the anaerobic mitochondrial metabolism of adultHymenolepis diminuta

“…Aside from the NADH-utilizing fumarate reductase (Scheibel et al 1968), H. diminuta mitochondria display a less active, inner membrane-associated, rotenone-sensitive and peroxide-forming NADH oxidase that appears to require tightly bound manganous ion. Peroxide is formed by NADPH oxidation as well (Fioravanti and Saz, 1980; Fioravanti, 1981, 1982 a ; McKelvey and Fioravanti, 1985; Fioravanti and Reisig, 1990). Both the NADH-utilizing fumarate reductase and oxidase exhibit a benzoquinone preference inasmuch as they employ rhodoquinone rather than ubiquinone as reflected in NADH oxidation, NADH-dependent oxygen consumption, hydrogen peroxide production, and succinate accumulation (Fioravanti and Kim, 1988).…”

The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites

“…Parasitic organisms, unlike its free-living counterparts, are under continuous attack by the chemical defense mechanisms of its host, which produce compounds such as H 2 O 2 and hypochlorous acid (HOCl) to contend with invaders [ 21 , 22 ] ( Figure 1 ). Furthermore, the complexity of the life cycle of a diversity of parasites expose them to variations in oxygen levels and hence to a broad range of oxidative stresses.…”