Succinate dehydrogenase, function

The covalent 8a-N(3)-histidyl FAD of mitochondrial succinate dehydrogenase functions as a two-electron acceptor in the oxidation of succinate to fumarate and as a one-electron donor in the reduction of the iron-sulfur centers of the enzyme. Recent ESR spectroscopic data have shown the covalent flavin semiquinone... 

Guest, J. R., 1981, Partial replacement of succinate dehydrogenase function hy phage- and plasmid-specified fumarate reductase in Escherichia coli, J. Gen. Microbiol. 122 1719179. 

Maklashina, E., Berthold, D. A., and Cecchini, G., 1998, Anaerobic expression of Escherichia coli succinate dehydrogenase functional replacement of fumarate reductase in the respiratory chain during anaerobic growth, J. Bacteriol. 180(22) 5989n5996. 

In addition to these more-or-less well characterized proteins, iron is known to be bound to certain flavoproteins such as succinic dehydrogenase (20), aldehyde oxidase (27), xanthine oxidase (22) and dihydrooro-tate dehydrogenase (23). Iron is present and functional in non-heme segments of the electron transport chain but again no real structural information is at hand (24). 

Succinate dehydrogenase is on the inner mitochondrial membrane, where it also functions as complex II of the electron transport chain. 

Cytochromes b of mitochondrial membranes are involved in passing electrons from succinate to ubiquinone in complex II138 and also from reduced ubiquinone to cytochrome c, in the 248-kDa complex III (Fig. 18-8). A similar complex is present in photosynthetic purple bacteria.123 139 Cytochrome b560 functions in the transport of electrons from succinate dehydrogenase to ubiquinone,138 and cytochrome b561 of secretory vesicle membranes has a specific role in reducing ascorbic acid radicals.140... 

The functions of the heme is uncertain. The soluble mammalian succinate dehydrogenase resembles closely that of E. coli and contains three Fe-S centers binuclear SI of E° 0 V, and tetranuclear S2 and S3 of -0.25 to -0.40 and + 0.065 V, respectively. Center S3 appears to operate between the -2 and -1 states of Eq. 16-17 just as does the cluster in the Chromatium high potential iron protein. The function of the very low potential S2 is not certain, but the following sequence of electron transport involving SI and S3 and the bound ubiquinone QD-S66 has been proposed (Eq. 18-4). 

Aspartate can be deaminated to fumarate by bacterial L-aspartate oxidase.2593 This flavoprotein is structurally and mechanistically related to succinate dehydrogenase and can function as a soluble fumarate reductase (p. 1027). However, its main function appears to be to permit the intermediate iminoaspartate to react with dihydroxyacetone-P to form quinolinate, which can be converted to NAD (see Fig. 25-ll).259b... 

At very high substrate concentrations deviations from the classical Michaelis-Menten rate law are observed. In this situation, the initial rate of a reaction increases with increasing substrate concentration until a limit is reached, after which the rate declines with increasing concentration. Substrate inhibition can cause such deviations when two molecules of substrate bind immediately, giving a catalytically inactive form. For example, with succinate dehydrogenase at very high concentrations of the succinate substrate, it is possible for two molecules of substrate to bind to the active site and this results in non-functional complexes. Equation S.19 gives one form of modification of the Michaelis-Menten equation. 

The classic example of competitive inhibition is inhibition of succinate dehydrogenase, an enzyme, by the compound malonate. Hans Krebs first elucidated the details of the citric acid cycle by adding malonate to minced pigeon muscle tissue and observing which intermediates accumulated after incubation of the mixture with various substrates. The structure of malonate is very similar to that of succinate (see Figure 1). The enzyme will bind malonate but cannot act further on it. That is, the enzyme and inhibitor form a nonproductive complex. We call this competitive inhibition, as succinate and malonate appear to compete for the same site on the enzyme. With competitive inhibition, the percent of inhibition is a function of the ratio between inhibitor and substrate, not the absolute concentration of inhibitor. 

Most anaerobically functioning mitochondria use endogenously produced fumarate as a terminal electron-acceptor (see before) and thus contain a FRD as the final respiratory chain complex (Behm 1991). The reduction of fumarate is the reversal of succinate oxidation, a Krebs cycle reaction catalysed by succinate dehydrogenase (SDH), also known as complex II of the electron-transport chain (Fig. 5.3). The interconversion of succinate and fumarate is readily reversible by FRD and SDH complexes in vitro. However, under standard conditions in the cell, oxidation and reduction reactions preferentially occur when electrons are transferred to an acceptor with a higher standard redox potential therefore, electrons derived from the oxidation of succinate to fumarate (E° = + 30 mV) are transferred by SDH to ubiquinone,... 

Ackrell BAC, Johnson MK, Gunsalus RP, Cecchini G (1992) Structure and function of succinate dehydrogenase and fumarate reductase. In Muller F (ed) Chemistry and biochemistry of flavoenzymes, vol III. CRC, Boca Raton, pp 229-297 Allen PC (1973) Helminths comparison of their rhodoquinone. Exp Parasitol 34 211-219... 

---