Malate dismutation

In this malate dismutation pathway, carbohydrates are degraded to phosphoenolpyruvate (PEP) via the classical glycolytic pathway. This PEP is then carboxylated by PEP carboxykinase (PEPCK) to oxaloacetate, which is subsequently reduced to malate. This malate is transported into the mitochondria and is degraded in a split pathway. A portion of the malate is oxidized to acetate and another portion is reduced to succinate, which can then be further metabolized to propionate (Fig. 20.1). 

In the oxidative branch of malate dismutation, malic enzyme oxidizes malate to pyruvate, which is then further oxidized to acetyl-CoA by pyruvate dehydrogenase, an enzyme complex specially adapted to anaerobic functioning in Ascaris suum and possibly in other parasitic helminths like the trematode F. hepatica and the cestode Dipylidium caninum (Diaz and Komuniecki, 1994 Klingbeil et al., 1996). Parasitic helminths like F. hepatica use an acetate succinate CoA-transferase (ASCT) for... 

Fig. 20.1. Generalized scheme of the main pathways of aerobic and anaerobic carbohydrate degradation in parasitic flatworms. The aerobic pathway is indicated by open arrows, whereas the anaerobic pathway (malate dismutation) is indicated by solid arrows. Abbreviations AcCoA, acetyl-CoA ASCT, acetateisuccinate CoA-transferase C, cytochrome c CI-CIV, complexes I—IV of the respiratory chain CITR, citrate FRD, fumarate reductase FUM, fumarate MAL, malate Methylmal-CoA, methylmalonyl-CoA OXAC, oxaloacetate PEP, phosphoenolpyruvate PROP, propionate Prop-CoA, propionyl-CoA PYR, pyruvate RQ, rhodoquinone SDH, succinate dehydrogenase SUCC, succinate Succ CoA, succinyl CoA UQ, ubiquinone.

Boxes indicate electron-transport chain complexes, whereas ovals represent the electron transporters UQ, RQ and cytochrome c. The open boxes represent complexes involved in the classical aerobic respiratory chain, whereas grey boxes represent complexes involved in malate dismutation. The vertical bar represents a scale for the standard redox potentials in mV. Translocation of protons by the complexes is indicated by H+ +. Abbreviations Cl, Clll and CIV, complexes I, III and IV of the respiratory chain cyt c, cytochrome c FRD, fumarate reductase Fum, fumarate SDH, succinate dehydrogenase Succ, succinate RQ, rhodoquinone UQ, ubiquinone. 

All parasitic flatworms capable of anaerobic metabolism favour malate as the primary mitochondrial substrate and the oxidative decarboxylations of first malate and then pyruvate generate intramitochondrial reducing power in the form of NADH (Fig. 20.1). In contrast, the pathways used to reoxidize intramitochondrial NADH are quite diverse and depend on the stage or species of parasite under examination, but in all cases, redox balance is maintained and electron-transport associated ATP is generated by the NADH-reduction of fumarate to succinate. In the cestode, hi. diminuta, succinate and acetate are the major end products of anaerobic malate dismutation and are excreted in the predicted 2 1 ratio. In the trematode F. hepatica, succinate is then further decarboxylated to propionate with an additional substrate level phosphorylation coupled to the decarboxylation of methylmalonyl CoA. F. hepatica forms primarily propionate and acetate as end products, again in a ratio of 2 1 to maintain redox balance. 

Parasitic stages, on the other hand, generally do not use oxygen as the final electron acceptor but use fermentative processes to obtain most of their ATP. For these stages, an uneconomical energy metabolism is not detrimental, as the host provides the nutrients. Most adult flatworms inside the final host produce end products of a fermentative carbohydrate breakdown, such as succinate, acetate, propionate and lactate. These end products are formed via malate dismutation, a fermentative pathway, which is present in all types of parasitic worms (flatworms as well as many nematodes), but which is also present in animals like freshwater snails, mussels, oysters and other marine organisms. Malate dismutation is linked to a specially... 

Catabolic pathways used Glycolysis, Krebs cycle Glycolysis, malate dismutation... 

Fig. 5.4. Two types of energy metabolism in cestodes. (a) Type 1 homolactate fermentation, (b) Type 2 Malate dismutation. Reaction 3 involves a carboxylation step decarboxylation occurs at 6, 7 and 10. Reducing equivalents are generated at reactions 6 and 7 one reducing equivalent is used at reaction 9. Thus, when the mitochondrial compartment is in redox balance and malate is the sole substrate, twice as much propionate as acetate is produced. Key 1, pyruvate kinase 2, lactate dehydrogenase 3, phosphoenolpyruvate carboxykinase 4, malate dehydrogenase 5, mitochondrial membrane 6 malic enzyme 7, pyruvate dehydrogenase complex 8, fumarase 9, fumarate reductase 10, succinate decarboxylase complex. indicates reactions at which ATP is synthesised from ADP cyt, cytosol mit, mitochondrion. (After Bryant Flockhart, 1986.)...

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