Oxidation of succinate

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

Consider the oxidation of succinate by molecular oxygen as carried out via the electron transport pathway... 

Succinyl-CoA derived from propionyl-CoA can enter the TCA cycle. Oxidation of succinate to oxaloacetate provides a substrate for glucose synthesis. Thus, although the acetate units produced in /3-oxidation cannot be utilized in glu-coneogenesis by animals, the occasional propionate produced from oxidation of odd-carbon fatty acids can be used for sugar synthesis. Alternatively, succinate introduced to the TCA cycle from odd-carbon fatty acid oxidation may be oxidized to COg. However, all of the 4-carbon intermediates in the TCA cycle are regenerated in the cycle and thus should be viewed as catalytic species. Net consumption of succinyl-CoA thus does not occur directly in the TCA cycle. Rather, the succinyl-CoA generated from /3-oxidation of odd-carbon fatty acids must be converted to pyruvate and then to acetyl-CoA (which is completely oxidized in the TCA cycle). To follow this latter route, succinyl-CoA entering the TCA cycle must be first converted to malate in the usual way, and then transported from the mitochondrial matrix to the cytosol, where it is oxida-... 

Co(lII) perchlorate oxidations of succinic, aspartic, maleic and fumaric acids all obey the rate expression ... 

Xanthothricin 308 stimulated oxidation of NADH and NAD-linked substrates by rat liver mitochondria, yeast mitochondria, and Ehrlich ascites tumor cells (74MI1, 74MI3). It also stimulated mitochondrial oxidation of succinate, pyruvate, or malate. The antibiotic xanthothricin was obtained... 

Succinate dehydrogenase is the enzyme that catalyzes the oxidation of succinate to fumarate and is also part of the respiratory chain 544 Malate dehydrogenase is one of several enzymes in the TCA cycle present in both the cytoplasm and mitochondria 544 Citrate is a multifunctional compound predominantly synthesized and released by astrocytes 544... 

Succinate dehydrogenase is the enzyme that catalyzes the oxidation of succinate to fumarate and is also part of the respiratory chain. It is bound tightly... 

Besides Szent-Gyorgi and Krebs, other groups were attacking the problem of carbohydrate oxidation. Weil-Malherbe suggested It is probable that the further oxidation of succinic acids passes through the stages of fumaric, malic, and oxaloacetic acid pyruvic acid is formed by the decarboxylation of the latter and the oxidative cycle starts again. K.A.C. Elliott, from the Cancer Research Laboratories at the University of Pennsylvania, also proposed a cycle via some 6C acid. 

Electrons enter the respiratory chain in various different ways. In the oxidation of NADH+H" by complex I, electrons pass via FMN and Fe/S clusters to ubiquinone (Q). Electrons arising during the oxidation of succinate, acyl CoA, and other substrates are passed to ubiquinone by succinate dehydrogenase or other mitochondrial dehydrogenases via en-... 

In studies with Isolated plant mitochondria, flavones, flava-nones, cinnamic acids, and benzoic acids were shown to Inhibit the oxidation of succinate, malate, and NADH Inhibition was... 

TCA cycle Oxidation of isocitrate, a-ketoglutarate, and malate Oxidation of succinate GDP GTP +6 +2 +2... 

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... 

Oxidation of Succinate to Fumarate The succinate formed from succinyl-CoA is oxidized to fumarate by the flavoprotein succinate dehydrogenase ... 

The experimental observation of a P/O ratio of 3 for oxidation of pyruvate and other substrates that donate NADH to the electron transport chain led to the concept that there are three sites for generation of ATP. It was soon shown that the P/O ratio was only 2 for oxidation of succinate. This suggested that one of the sites (site I) is located between NADH and ubiquinone and precedes the diffusion of QH2 formed in the succinate pathway to complex III. 

The stoichiometry of proton pumping was measured by Lehninger and associates using a fast-responding 02 electrode and a glass pH electrode.189 190 They observed an export of eight H+/ O for oxidation of succinate rat liver mitochondria in the presence of a permeant cation that would prevent the buildup of Em, and four H+/ O (2 H+/ e ) for the cytochrome oxidase system. These are equivalent to two H+/ e at each of sites II and III as is indicated in Fig. 18-4. 

Succinate Dehydrogenase Catalyzes the Oxidation of Succinate to Fumarate Fumarase Catalyzes the Addition of Water to Fumarate to Form Malate Malate Dehydrogenase Catalyzes the Oxidation of Malate to Oxaloacetate... 

Succinate Dehydrogenase Catalyzes the Oxidation of Succinate to Fumarate... 

The next step in the TCA cycle, the oxidation of succinate to fumarate, involves insertion of a double bond into a saturated hydrocarbon chain. 

Current estimates are that three protons move into the matrix through the ATP-synthase for each ATP that is synthesized. We see below that one additional proton enters the mitochondrion in connection with the uptake of ADP and Pi and export of ATP, giving a total of four protons per ATP. How does this stoichiometry relate to the P-to-O ratio When mitochondria respire and form ATP at a constant rate, protons must return to the matrix at a rate that just balances the proton efflux driven by the electron-transport reactions. Suppose that 10 protons are pumped out for each pair of electrons that traverse the respiratory chain from NADH to 02, and 4 protons move back in for each ATP molecule that is synthesized. Because the rates of proton efflux and influx must balance, 2.5 molecules of ATP (10/4) should be formed for each pair of electrons that go to 02. The P-to-O ratio thus is given by the ratio of the proton stoichiometries. If oxidation of succinate extrudes six protons per pair of electrons, the P-to-O ratio for this substrate is 6/4, or 1.5. These ratios agree with the measured P-to-O ratios for the two substrates. 

Rat liver mitochondria were isolated as described (4). The initial rate of ATP synthesis associated with the oxidation of succinate was followed by monitoring fluorometrically the ATP-linked NADPH production in the presence of hexokinase and glucose-6-phosphate dehydrogenase (10). Control experiments showed no interference from unexpected reduction of NADP+ or from electron backflow. Possible ATP formation via mitochondrial adenylate... 

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

Electron transport Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate in the from FADH2 citric acid cycle (Topic LI). The succinate dehydrogenase contains bound FAD... 

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,... 

Answer From the difference in standard reduction potential (AE °) for each pair of halfreactions, we can calculate the AG ° values for the oxidation of succinate using NAD+ and oxidation using E-FAD. 

The oxidation of succinate by E-FAD is favored by the negative standard free-energy change, which is consistent with aK eq of >1. Oxidation by NAD+ would require a large, positive, standard free-energy change and have a K eq favoring the synthesis of succinate. 

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