Fumarate reduction

Van Hellemond, J.J., Van Remoortere, A. and Helens, A.C.M. (1997) Schistosoma mansoni sporocysts contain rhodoquinone and produce succinate by fumarate reduction. Parasitology 115, 1 77-182. 

Next to fumarate reduction, some organisms use specific reactions in lipid biosynthesis as an electron sink to maintain redox balance in anaerobically functioning mitochondria. In anaerobic mitochondria two variants are known the production of branched-chain fatty acids and the production of wax esters. The parasitic nematode Ascaris suum reduces fumarate in its anaerobic mitochondria, but instead of only producing acetate and succinate or propionate, like most other parasitic helminths, this organism also use the intermediates acetyl-CoA and propionyl-CoA to form branched-chain fatty acids (Komuniecki et al. 1989). This pathway is similar to reversal of P-oxidation and a complex mixture of the end products acetate, propionate, succinate and branched-chain fatty acids is excreted. In this pathway, the... 

Fumarate reduction is the most commonly used electron-sink for the reoxidation of reduced cofactors in anaerobically functioning mitochondria (see before). Fumarate reduction is catalysed in these mitochondria by a FRD complex, which is structurally very similar to the SDH complexes present in... 

The fumarate molecule is in van der Waals contact with the isoallox-azine ring of FAD. The linear arrangement of the prosthetic groups in one QFR complex therefore provides one straightforward pathway by which electrons could be transferred efficiently from the menaquinol oxidizing site via the two heme groups, the three iron—sulfur clusters, and the FAD to the site of fumarate reduction. 

In addition to the transfer of electrons, two protons are bound on fumarate reduction (see reaction 1) and two protons are liberated on menaquinol oxidation (see reaction 2). The protons consumed on fumarate reduction are undoubtably bound from the cytoplasm (see Fig. 8a). The experimental results on intact bacteria, with inverted vesicles or liposomes containing W. succinogenes QFR (Kroger et al., 2002 Biel et al., 2002), suggest that the oxidation of menaquinol by fumarate as catalyzed by W. succinogenes QFR is an electroneutral process. The protons formed by menaquinol oxidation have therefore been assumed to be released to the cytoplasmic side of the membrane where they balance the protons consumed by fumarate reduction. 

Fig. 9. The coupling of electron and proton flow in succinate iquinone oxidoreduc-tases in aerobic (a,c) and anaerobic respiration (b,d), respectively. Positive and negative sides of the membrane are as described for Fig. 1. (a) and (b) Electroneutral reactions as catalyzed by C-type SQR enzymes (a) and D-type E. coli QFR (b). (c) Utilization of a transmembrane electrochemical potential Ap as possibly catalyzed by A-type and B-type enzymes, (d) Electroneutral fumarate reduction by B-type QFR enzymes with a proposed compensatory E-pathway. ...

Both the membrane-bound and the soluble succinate dehydrogenases are capable of catalyzing fumarate reduction in the presence of a suitable electron donor such as FMNHa. In the mammalian enzyme, this activity is not more than a few percent of the succinate-PMS reductase activity (23, 25). Ringler and Singer (177) have also shown that in brain mito-... 

The two subunits resolved by Davis and Hatefi (143, 166) by the use of chaotropes and freeze-thawing were inactive, separately and in combination, for succinate oxidation or fumarate reduction. However, the possibilities have not been fully explored. Nor has this sort of resolution been performed on the cyanide-treated enzyme to see whether one or the other subunit can be preferentially modified. Further work in these areas might... 

How eould this eatalytie bias be controlled One possibility is that the proton transfer pathway eould eontribute to specifieity (Peters et al., 1998). Another possibility is that differences in midpoint potential of the FeS clusters (or other redox sites) that constitute the intramolecular wire could be tuned to facilitate one of the two directions of the reaction. For example, these redox sites could best match the midpoint potentials of a particular oxidized or reduced electron carrier (Holm and Sander, 1999). Apparently, a conformational change in succinate dehydrogenase, coupled to the reduction of FAD, is responsible for its catalytic bias for fumarate reduction (Hirst et al., 1996). 

Experiments carried out with equal concentrations of fumarate and succinate in solution reveal that at pH values below 7.5, succinate dehydrogenase is inherently biased to function better in the direction of fumarate reduction. This is easily observed despite the instability of SdhAB (an interesting contrast with FrdAB) since successive cycles trace... 

Macy, J., Probst, I., and Gottschalk, G., "Evidence for Cytochrome Involvement in Fumarate Reduction and ATP Synthesis by Bacteroides fragilis in the Presence of Hemin," J. Bacteriol. 123, 436-442 (1975). 

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