Succinate dehydrogenase, reaction

FIGURE 20.14 The succinate dehydrogenase reaction. Oxidation of succinate occurs with reduction of [FAD]. Reoxidation of [FADH9] transfers electrons to coenzyme Q. 

Note that flavin coenzymes can carry out either one-electron or two-electron transfers. The succinate dehydrogenase reaction represents a net two-electron reduction of FAD. 

The fatty acyl-CoA dehydrogenase reaction is analogous to the succinate dehydrogenase reaction both are FAD-requiring oxidations ... 

Fig. 4. In the succinate dehydrogenase reaction, iwo non-equivalent hydrogen atoms are removed by tram elimination.

Riboflavin is utilized in the synthesis of FAD, which is used in the succinate dehydrogenase reaction. FAD is also required by a-ketoglutarate dehydrogenase and pyruvate dehydrogenase. 

Inhibition of Succinate Dehydrogenase A classic example of competitive inhibition occurs with the succinate dehydrogenase reaction ... 

Retey et al. (72) used this same principle in their work on the stereochemistry of citrate formation from chiral acetyl-CoA with Si-citrate synthase (Scheme 15). The chiral methyl group was converted into one of the methylene groups of succinate and the distinction between sets (I, 2, 3) and (4, 5, 6) was then based on the known different isotope effects for the removal of pro-/ ( hMd = 5.3 kH/kT = 12) vs. pro-5 (kH/kD = 1.35 kH/kj = 1.5) hydrogens of succinate in the succinate dehydrogenase reaction (73). However, the malate synthase/fumarase procedure is clearly the most commonly used method to analyze the configuration and chiral purity of chiral methyl groups. 

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). 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

Figure 9.2 Summary of reactions of the Krebs cycle. The names of the enzymes are dtrate synthase, aconitase, isodtrate dehydrogenase (there are two enzymes, one ubTizes NAD as the cofactor, the other NADPT it is assumed that the NAD -specific enzyme is that involved in the cycle), oxoglutarate dehydrogenase, sucdnyl CoA synthetase, succinate dehydrogenase, fumarate hydratase, malate dehydrogenase.

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. 

Quantitative conversion of the iron in succinate dehydrogenase to this form is possible if additional cysteine is added to the reaction mixture. It is probable that not enough cysteinyl sulfur ligands are available for complex formation without addition of the extra cysteine some of the nitrosyl complex does form without any cysteine addition in these systems. 

The oxygen reactivity of flavohydroquinone bound to apoflavoprotein dehydrogenases can vary considerably from fast (flavodoxins), moderate (xanthine oxidase) to nil (succinate dehydrogenase) Most, but not all, flavoprotein dehydrogenases contain one or more types of metal prosthetic groups, e.g. xanthine oxidase contains also Fe and Mo. Since these metal ions are involved in electron flux, their possible participation in the reaction with O2 cannot be excluded. Much evidence, however, indicates that the flavin is involved in the one-electron reduction of Oj, as shown in Equation (5). 

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... 

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