Energy Metabolisms of Parasitic Helminths: Adaptations to Parasitism

Abstract

Many metazoans, and particularly the parasitic forms, have adapted well to their environments. This is particularly obvious in organisms that reside in anoxic surroundings, such as the large lumen-dwelling intestinal parasites. However, anaerobic energy metabolisms are not confined to parasites in microaerophilic environments. Some that reside in highly aerobic surroundings (e.g. blood or lungs) also have lost much or all of their aerobic capabilities for energy generation. Adaptations toward anaerobiosis are many and varied: homolactate fermentation (schistosomes and filarial worms), heterolacate fermentations (H. diminuta), and succinate and heterosuccinate fermentations (Ascaris). Even helminths that are obligate aerobes are not complete oxidizers. All accumulate aerobic fermentation products, indicating at best a limited terminal respiration. Some worms, particularly some of the larval stages, retain their ability to survive anaerobically but require the presence of oxygen for motility. Regardless of the type of oxygen requirement, all parasitic helminths examined are dramatically different from their mammalian hosts in regard to their energy metabolisms. Many similar adaptations have been shown to occur in nonparasitic organisms ranging from metazoans, through fish and mammals. There is much room for additional studies of these biochemical adaptations.

Rhodoquinone and Complex II of the Electron Transport Chain in Anaerobically Functioning Eukaryotes

“…The opposite, however, that enzyme complexes known to reduce fumarate in vivo show positive-order kinetics, was not observed as adult A. suum (17) and F. hepatica (Fig. 3), although both completely dependent on fumarate reductase activity (32,40), showed diode-like behavior (negative order). Adult H. contortus (Fig.…”

Ethanol formation in adh0 mutants reveals the existence of a novel acetaldehyde-reducing activity in Saccharomyces cerevisiae

“…For example, a key reaction in the anaerobic carbohydrate dissimilation of the helminth Ascaris lumbricoides is the formation of succinate from fumarate as a terminal electron acceptor by fumarate reductase, a pyridine nucleotide-linked enzyme of the inner mitochondrial membrane. In this organism the fumarate reductase reaction appears to provide a major source of mitochondrial ATP in Ascaris muscle metabolism (28). Thus, because of the tight connection to the respiratory chain, a similar role might be postulated for this novel ethanol-forming enzyme in S. cerevisiae.…”

“…Moreover, the fact that ethanol production is linked to intact organelles may suggest that the ethanol-forming enzyme is associated with the inner mitochondrial membrane. Whether such a membrane-associated acetaldehyde reductase reaction is coupled directly to an electron transport-associated phosphorylation, as shown for the fumarate reductase reaction in the anaerobic metabolism of many parasites and bacteria (16,28), cannot yet be decided. For example, a key reaction in the anaerobic carbohydrate dissimilation of the helminth Ascaris lumbricoides is the formation of succinate from fumarate as a terminal electron acceptor by fumarate reductase, a pyridine nucleotide-linked enzyme of the inner mitochondrial membrane.…”

Crystallographic Studies on Ascaris suum NAD-Malic Enzyme Bound to Reduced Cofactor and Identification of an Effector Site

“…Because of its functional importance, the enzyme has been isolated and characterized from several sources (3,6). The mitochondrial NAD-malic enzyme (m-NAD⅐ME) from the parasitic nematode, Ascaris suum, plays a pivotal role in carbohydrate metabolism in parasitic worms (7). In the anaerobic metabolism of A. suum, malate, an intermediate in the worm's glycolytic pathway, is transported into the mitochondria where it undergoes a dismutation and is converted to pyruvate and NADH via the malic enzyme reaction and to fumarate via the fumarase reaction.…”