Iron-sulfur proteins succinate dehydrogenase

Wachtershanser has also suggested that early metabolic processes first occurred on the surface of pyrite and other related mineral materials. The iron-sulfur chemistry that prevailed on these mineral surfaces may have influenced the evolution of the iron-sulfur proteins that control and catalyze many reactions in modern pathways (including the succinate dehydrogenase and aconitase reactions of the TCA cycle). 

Complex II The Succinate Dehydrogenase Complex. Succinate dehydrogenase is the only enzyme of the TCA cycle that is embedded in the inner membrane. Its four subunits include two iron-sulfur proteins, one of which also has a covalently attached FAD. As in NADH dehydrogenase, the substrate-oxidation site is on the matrix side of the membrane (fig. 14.10). 

ESR studies on fumarate reductase in situ have suggested1436 the presence of two [2Fe-2S] clusters and a HiPIP cluster. Examination of the occurrence of cysteine residues in the two peptides and a comparison with succinate dehydrogenase suggests that the two-iron centres are in the smaller iron-sulfur protein, while the [4Fe-4S] centre may be in either subunit. 

Fig. 18. Thermodynamic profile of iron-sulfur centers in pigeon heart mitochondria SDH, succinate dehydrogenase Rieske s Fe/S, iron-sulfur protein of complex III. From Ohnishi (ISl).

The subunits separated by the above technique indicated a distribution of iron and labile sulfide as shown in Table X. Thus the larger subunit contained flavin, iron, and labile sulfide in the approximate ratio of 1 4 4, while the smaller subunit appeared to have the characteristics of a soluble iron-sulfur protein. The absorption spectra of succinate dehydrogenase and its two subunits analyzed to show the contributions of flavin and the iron-sulfur chromophore in each preparation are given in Fig. 27. 

Both groups of reactions are found in bacteria (14), all higher animals (i5), and plants (16) however, oxidative phosphorylation is responsible for 90 % of the oxygen consumed (i 7). Oxidative phosphorylation is driven by the respiratory electron-transport system that is embedded in the lipoprotein inner membrane of eukaryotic mitochondria and in the cell membrane of prokaryotes. It consists of four complexes (Scheme I). The first is composed of nicotinamide adenine dinucleotide (NADH) oxidase, flavin mononucleotide (FMN), and nonheme iron-sulfur proteins 18,19), and it transfers electrons from NADH to ubiquinone. The second is composed of succinate dehydrogenase (SDH), flavin adenine dinucleotide (FAD), and nonheme iron-sulfur proteins (20), and it transfers electrons from succinate to ubiquinone 21, 22). The third is composed of cytochromes b and c, and nonheme iron-sulfur proteins (23), and it transfers electrons from ubiquinone (UQ) to cytochrome c 24). The fourth complex consists of cytochrome c oxidase [ferrocytochrome c 0 oxidoreductase EC 1.9.3.1 25)] which transfers electrons from cytochrome c to O2 26, 27). 

Abbreviations FAD, flavin adenine dinucleotide Fe-S, iron-sulfur proteins that can he identified in separate clusters by electron paramagnetic resonance analysis (the s-1, s-2 subscripts identify these iron-sulfur proteins as part of the succinate dehydrogenase complex) His, the histidine linkage between FAD and the large (70,000 daltons) protein moiety of the enzyme FMN, flavin mononucleotide N-la, N-2 subscripts identify these iron-sulfur proteins as part of the NADH-dehydro-genase complex UQ, ubiquinone Cyt bf and Cyt b, cytochrome b-566 and b-563, respectively. 

The succinate dehydrogenase complex (complex II) consists primarily of the citric acid cycle enzyme succinate dehydrogenase and two iron-sulfur proteins. Complex II mediates the transfer of electrons from succinate to UQ. The... 

Complex II (succinate dehydrogenase) - Complex II is not in the path traveled by electrons from Complex I (Figure 15.3). Instead, it is a point of entry of electrons from FADH2 produced by the enzyme succinate dehydrogenase in the citric acid cycle. Both complexes I and II donate their electrons to the same acceptor, coenzyme Q. Complex II, like complex I, contains iron-sulfur proteins, which participate in electron transfer. It is also called succinate-coenzyme Q reductase because its electrons reduce coenzyme Q. 

Succinate dehydrogenase, like aconitase, is an iron—sulfur protein. Indeed, succinate dehydrogenase contains three different kinds of iron—sulfur clusters, 2Fe-2S (two iron atoms bonded to two inorganic sulfides), 3Fe-4S, and 4Fe-4S. Succinate dehydrogenase— which consists of two subunits, one 70 kd and the other 27 kd—differs from other enzymes in the citric acid cycle in being embedded in the inner mitochondrial membrane. In fact, succinate dehydrogenase is directly associated with the electron-transport chain, the link between the citric acid cycle and ATP formation. FADH2 produced by the... 

Succinate dehydrogenase contains iron atoms hut does not contain a heme group it is referred to as a nonheme iron protein or an iron-sulfur protein. The latter name refers to the fact that the protein contains several clusters that consist of four atoms each of iron and of sulfur. 

Succinate-Q reductase (complex II) contains succinate dehydrogenase, FAD, two iron-sulfur centers, and an additional iron-sulfur protein. As with complex I, the substrate binding site of succinate reductase is also on the M side of the membrane (Hatefi and Stiggall, 1976). 

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