Succinate dehydrogenase reactions involving

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.

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). 

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

Acetyl-CoA is oxidized to C02 by the Krebs cycle, also called the tricarboxylic acid cycle or citric acid cycle. The origin of the acetyl-CoA may be pyruvate, fatty acids, amino acids, or the ketone bodies. The Krebs cycle may be considered the terminal oxidative pathway for all foodstuffs. It operates in the mitochondria, its enzymes being located in their matrices. Succinate dehydrogenase is located on the inner mitochondrial membrane and is part of the oxidative phosphorylation enzyme system as well (Chapter 17). The chemical reactions involved are summarized in Figure 18.7. The overall reaction from pyruvate can be represented by Equation (18.5) ... 

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. 

A procedure for determining the absolute configuration of the tritiated succinic acid had already been developed, which involved partial oxidation on succinate dehydrogenase [45]. Applying this method it was then possible to show that the tritiated succinic acid of interest had the (S) configuration, and this in turn established the (5S) configuration of the tritiated /3-lysine from which it had been derived. Inspection of Fig. 28 reveals that the /3-lysine mutase reaction takes place with inversion at the C-5 of the substrate. 

Both classes of enzymes are involved in a wide range of redox reactions, e.g. succinate dehydrogenase and xanthine oxidase. 

Historically, individual enzymes were identified using the name of the substrate or group upon which the enzyme acts and then adding the suffix -ase. For example, the enzyme hydrolyzing urea was urease. Later, the type of reaction involved was also identified, as in carbonic anhydrase, D-amino acid oxidase, and succinate dehydrogenase. In addition, some enzymes had been given empirical names such as trypsin, diastase, ptyalin, pepsin, and emulsin. 

Oxidation/reduction reactions involve the transfer of electrons from a molecule being oxidized (the electron donor) to a molecule being reduced (the electron acceptor). Because one or more electrons are transferred, neither oxidation nor reduction can occur without the other occurring simultaneously. An example of an oxidation/reduction reaction is the following reaction, catalyzed by succinate dehydrogenase, from the citric acid cycle ... 

Figure 31. An electron transport system and redox potentials in mitochondria. FMN refers to Flavin mononucleotide in NADH2 dehydrogenase, FAD refers to Flavin adenine dinucleotide in succinate dehydrogenase, I, II, and III correspond to the reaction processes which may be involved in phosphorylation, Fe—S non-heme iron, Cyt Heme in cytochromes (after ref. 171).

Riboflavin is an important constituent of the flavoproteins.The prosthetic group of these compound proteins contains riboflavin in the form of the phosphate (flavin mononucleotide, FMN) or in a more complex form as flavin adenine dinucleotide (FAD). There are several flavoproteins that function in the animal body they are all concerned with chemical reactions involving the transport of hydrogen. Further details of the importance of flavoproteins in carbohydrate and amino acid metabolism are discussed in Chapter 9. Flavin adenine dinucleotide plays a role in the oxidative phosphorylation system (see Fig. 9.2 on p. 196) and forms the prosthetic group of the enzyme succinic dehydrogenase, which converts succinic acid to fumaric acid in the citric acid cycle. It is also the coenzyme for acyl-CoA dehydrogenase. 

Metallo-Flavoproteins. As was mentioned in the case of cytochrome reductase, enzymes are known that contain metal cofactors in addition to flavin. These are called metallo-flavoproteins. The presence of metals introduces complexity into the reaction, since the metals involved, iron, molybdenum, copper, and manganese, all exist in at least two valence states and can participate in oxidation-reduction reactions. The enzymes known to be metallo-flavoproteins include xanthine oxidase, aldehyde oxidase, nitrate reductase, succinic dehydrogenase, fatty acyl CoA dehydrogenases, hydrogenase, and cytochrome reductases. Before these are discussed in detail some physical properties of flavin will be presented. 

Cytochromes in Mitochondria. The majority of cytochromes occur entirely in mitochondria, where they are associated with large amounts of lipid. An intimate association exists between the cytochromes and succinic dehydrogenase to form succinoxidase, which retains the ability to oxidize succinate after all other oxidative reactions have been washed out of the particles. The activity of the succinoxidase system is sensitive to many environmental factors, which apparently influence the physical state of the particles. When mitochondria are exposed to distilled water, for example, cytochrome c is lost. Exogenous cytochrome c is used much less efficiently than particle-bound cytochrome. It is concluded from observations of this sort that the individual components, succinic dehydrogenase, cytochrome c, cytochrome a, and cytochrome oxidase, together with any other factors that may be involved, are fixed in position to react rapidly with each other, and do not depend on diffusion. 

Fig. 60. The respiratory chain of higher plants. Ubiquinone appears to serve as an electron reservoir. = probable site of ATP formation. SD = succinate dehydrogenase. It used to be assumed that, with the exception of the reaction catalyzed by SD, the hydrogen acceptor in dehydrogenation reactions was NAD+ and that the hydrogen then entered the respiratory chain in the form of NADH+H+. In reality the situation is more complicated since the lipoic acid oxidizing flavoproteid of the pyruvate dehydrogenase and the a-ketoglutarate dehydrogenase complexes—in both cases the same flavoproteid is involved—can establish direct contact with the flavoproteins of the respiratory chain just like succinate dehydrogenase. associated with encircled flavoproteins means that ATP can be formed as a result of transitions between the various flavoproteins, except those involving SD.

---