Citric acid cycle succinate dehydrogenase

The conversion of oxaloacetate to succinate is catalyzed by enzymes of the citric acid cycle malate dehydrogenase, fumarase and succinate dehydrogenase. These enzymes were isolated from the cells of P. shermanii... 

As a result of oxidations catalyzed by the dehydrogenases of the citric acid cycle, three molecules of NADH and one of FADHj are produced for each molecule of acetyl-CoA catabohzed in one mrn of the cycle. These reducing equivalents are transferred to the respiratory chain (Figure 16-2), where reoxidation of each NADH results in formation of 3 ATP and reoxidation of FADHj in formation of 2 ATP. In addition, 1 ATP (or GTP) is formed by substrate-level phosphorylation catalyzed by succinate thiokinase. 

Four of the B vitamins are essential in the citric acid cycle and therefore in energy-yielding metabolism (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor in the a-ketoglutarate dehydrogenase complex and in succinate dehydrogenase (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD),... 

FADH is produced by succinate dehydrogenase in the citric acid cycle and by the a-glycerol phosphate shuttle. Both enzymes are located in the inner membrane and can reoxidize FADHj directly by transferring electrons into the ETC. Once FADH2 has been oxidized, the FAD can be made available once again for use by the enzyme. 

Balance Sheet for the Citric Acid Cycle The citric acid cycle has eight enzymes citrate synthase, aconitase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, and malate dehydrogenase. 

Fig. 3. Krebs citric acid cycle. Enzymes involved (1) Condensing enzyme (2) aconitase (3) isocitric acid (4) a-ketoglucaric acid dehydrogenase (4) a succinic acid thiokinasc (5) succinic acid dehydrogenase (6) fumarasc (7) malaic acid dehydrogenase. Abbreviations CA = citric acid ACOM = eij-aconitic acid KG = a-ketoglutaric acid SIC = succinic acid FA = fumaric acid MA = malic acid OA = oxalaceiic acid...

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... 

The citric acid cycle operates in the mitochondria of eukaryotes and in the cytosol of prokaryotes. Succinate dehydrogenase, the only membrane-bound enzyme in the citric acid cycle, is embedded in the inner mitochondrial membrane in eukaryotes and in the plasma membrane in prokaryotes. 

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... 

The classic example of competitive inhibition is inhibition of succinate dehydrogenase, an enzyme, by the compound malonate. Hans Krebs first elucidated the details of the citric acid cycle by adding malonate to minced pigeon muscle tissue and observing which intermediates accumulated after incubation of the mixture with various substrates. The structure of malonate is very similar to that of succinate (see Figure 1). The enzyme will bind malonate but cannot act further on it. That is, the enzyme and inhibitor form a nonproductive complex. We call this competitive inhibition, as succinate and malonate appear to compete for the same site on the enzyme. With competitive inhibition, the percent of inhibition is a function of the ratio between inhibitor and substrate, not the absolute concentration of inhibitor. 

Answer The flavin nucleotides, FMN and FAD, would not be synthesized. Because FAD is required by the citric acid cycle enzyme succinate dehydrogenase, flavin deficiency would strongly inhibit the cycle. 

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. 

There are four major regulatory enzymes in the citric acid cycle. These are citrate synthase (step 1), isocitrate dehydrogenase (step 3), 2-oxoglutarate dehydrogenase (step 4), and succinate dehydrogenase (step 6). 

Pyruvate can be converted to acetyl-CoA via the pyruvate dehydrogenase complex. Pyruvate can also be carboxylated via pyruvate carboxylase to produce oxaloacetate. So, two molecules of pyruvate can form the precursors of citrate, which can be converted to succinate within the citric acid cycle. 

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) ... 

Mercury interferes with mitochondrial oxidation in the brain through mercaptide formation with thiol groups in pyruvate oxidase. Succinic dehydrogenase of the citric acid cycle is also inhibited. 

Succinate dehydrogenase is the only enzyme of the citric acid cycle which is bound to the inner membrane of mitochondria. It is also one of three flavoproteins known in which flavin is covalently linked to the protein. The other two are monoamine oxidase of the outer membrane of liver mitochondria (138) and Chromatium cytochrome c-552 (139). 

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

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