Succinate dehydrogenase, reaction catalyzed

Mitochondrial succinate dehydrogenase, which catalyzes the reaction of Eq. 15-21, contains a flavin prosthetic group that is covalently attached to a histidine side chain. This modified FAD was isolated and identified as 8a-(Ne2-histidyl)-FAD 219 The same prosthetic group has also been found in several other dehydrogenases.220 It was the first identified member of a series of modified FAD or riboflavin 5 -phosphate derivatives that are attached by covalent bonds to the active sites of more than 20 different enzymes.219... 

Reaction 6. Succinate dehydrogenase then catalyzes the oxidation of succinate to fumarate in the next step. The oxidizing agent,//op/m adenine dinucleotide (FAD), is reduced in this step ... 

Step 6. Formation of Fumarate—FAD-Linked Oxidation Succinate is oxidized to fumarate, a reaction that is catalyzed by the enzyme succinate dehydrogenase. This enzyme is an integral protein of the inner mitochondrial membrane. We shall have much more to say about the enzymes bound to the inner mitochondrial membrane in Ghapter 20. The other individual enzymes of the citric acid cycle are in the mitochondrial matrix. The electron acceptor, which is FAD rather than NADA is covalently bonded to the enzyme succinate dehydrogenase is also called a flavoprotein because of the presence of FAD with its flavin moiety. In the succinate dehydrogenase reaction, FAD is reduced to FADHo and succinate is oxidized to fumarate. 

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). 

Succinate dehydrogenase (ubiquinone) [EC 1.3.5.1], a multiprotein complex found in the mitochondria, catalyzes the reaction of succinate with ubiquinone to produce fumarate and ubiqumol. The enzyme requires FAD and iron-sulfur groups. It can be degraded to form succinate dehydrogenase [EC 1.3.99.1], a FAD-dependent system that catalyzes the reaction of succinate with an acceptor to produce fumarate and the reduced acceptor, but no longer reacts with ubiquinone. 

Fumarate is able to serve as an electron acceptor in anaerobic respiration, as it may be reduced reversibly to succinate in a two-electron process. The succinate-fumarate couple may therefore be utilized as an oxidant or reductant in the respiratory chain, and so differs from the other examples given in this section. These two reactions are catalyzed by succinate dehydrogenase and fumarate reductase, which have many similarities in subunit structure. These are shown in Table 29. Although they are different enzymes, the fumarate reductase can substitute for succinate dehydrogenase under certain conditions. The synthesis of succinate dehydrogenase is induced... 

Three modifications of the conventional oxidative citric acid cycle are needed, which substitute irreversible enzyme steps. Succinate dehydrogenase is replaced by fumarate reductase, 2-oxoglutarate dehydrogenase by ferredoxin-dependent 2-oxoglutarate oxidoreductase (2-oxoglutarate synthase), and citrate synthase by ATP-citrate lyase [3, 16] it should be noted that the carboxylases of the cycle catalyze the reductive carboxylation reactions. There are variants of the ATP-driven cleavage of citrate as well as of isocitrate formation [7]. The reductive citric acid... 

Oxidation of succinate to fumarate (catalyzed by succinate dehydrogenase the reaction involves FAD). 

UQ may also be reduced by complex II (succinate ubiquinone oxido-reductase, succinate dehydrogenase), which contains four polypeptide chains, molecular weights 70,000, 27,000, 15,500, and 13,500. The first two constitute bona fide succinate dehydrogenase, a Krebs cycle enzyme catalyzing reaction... 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

The enzyme succinate dehydrogenase (Chaps. 12 and 14) catalyzes the reaction ... 

Succinate dehydrogenase catalyzes the so-called trans elimination of two H s. This is the only reaction in the citric acid cycle involving FAD, and succinate dehydrogenase is the only enzyme in the cycle that is membrane-bound. The importance of this will be discussed in Chap. 14. 

The formation of acetyl-CoA from pyruvate in animals is via the pyruvate dehydrogenase complex, which catalyzes the irreversible decarboxylation reaction. Carbohydrate is synthesized from oxaloacetate, which in turn is synthesized from pyruvate via pyruvate carboxylase. Since the pyruvate dehydrogenase reaction is irreversible, acetyl-CoA cannot be converted to pyruvate, and hence animals cannot realize a net gain of carbohydrate from acetyl-CoA. Because plants have a glyoxylate cycle and animals do not, plants synthesize one molecule of succinate and one molecule of malate from two molecules of acetyl-CoA and one of oxaloacetate. The malate is converted to oxaloacetate, which reacts with another molecule of acetyl-CoA and thereby continues the reactions of the glyoxylate cycle. The succinate is also converted to oxaloacetate via the enzymes of the citric acid cycle. Thus, one molecule of oxaloacetate is diverted to carbohydrate synthesis and, therefore, plants are able to achieve net synthesis of carbohydrate from acetyl-CoA. 

In the succinate dehydrogenase-catalyzed reaction, why is the appropriate electron acceptor FAD rather than NAD+, which is used in the other redox reactions of the citric acid cycle (Chap. 12) ... 

Examples of Rapid Reversible Inhibitors. Competitive inhibitors are often similar in structure to one of the substrates of the reaction they are inhibiting. Inhibitors of this type are sometimes called substrate analogs and their binding affinity (K ) usually approximates that of the substrate. One of the first reactions inhibited by a substrate analog was that catalyzed by succinate dehydrogenase (Equation 17.24). 

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