Citric acid cycle pyruvate dehydrogenase

The conversion occurs through a multistep sequence of reactions catalyzed by a complex of enzymes and cofactors called the pyruvate dehydrogenase complex. The process occurs in three stages, each catalyzed by one of the enzymes in the complex, as outlined in Figure 29.11 on page 1152. Acetyl CoA, the ultimate product, then acts as fuel for the final stage of catabolism, the citric acid cycle. All the steps have laboratory analogies. 

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

Thiamine pyrophosphate is a coenzyme for several enzymes involved in carbohydrate metabolism. These enzymes either catalyze the decarboxylation of oi-keto acids or the rearrangement of the carbon skeletons of certain sugars. A particularly important example is provided by the conversion of pyruvic acid, an oi-keto acid, to acetic acid. The pyruvate dehydrogenase complex catalyzes this reaction. This is the key reaction that links the degradation of sugars to the citric acid cycle and fatty acid synthesis (chapters 16 and 18) ... 

To begin with, let us return to the aerobic catabolism of simple sugars such as glucose to yield two molecules of pyruvate -I- two molecules of ATP - - two molecules of NADH. We noted just above that coupling the oxidation of the two molecules of NADH to the electron transport chain yields an additional six molecules of ATP, three for each molecule of NADH, for a total of eight. Now let s ask what happens when we further metabolize the two molecules of pyruvate via the pyruvate dehydrogenase complex and the citric acid cycle. 

Pyruvate dehydrogenase a-Ketoglutarate dehydrogenase Synthesis of acetyl-CoA 1 Citric acid cycle [ B /P R2—C—C o- O R2—cf S-CoA... 

Pyruvate, the product of glycolysis, is converted to acetyl-CoA, the starting material for the citric acid cycle, by the pyruvate dehydrogenase complex. 

TABLE 16-1 Stoichiometry of Coenzyme Reduction and ATP Formation in the Aerobic Oxidation of Glucose via Glycolysis, the Pyruvate Dehydrogenase Complex Reaction, the Citric Acid Cycle, and Oxidative Phosphorylation... 

The overall rate of the citric acid cycle is controlled by the rate of conversion of pyruvate to acetyl-CoA and by the flux through citrate synthase, isocitrate dehydrogenase, and a-lcetoglutarate dehydrogenase. These fluxes are largely determined by the concentrations of substrates and products the end products ATP and NADH are inhibitory, and the substrates NAD+ and ADP are stimulatory. 

The mitochondrial matrix, enclosed by the inner membrane, contains the pyruvate dehydrogenase complex and the enzymes of the citric acid cycle, the fatty... 

Lactate consumption The direction of the lactate dehydrogenase reaction depends on the relative intracellular concentrations of pyruvate and lactate, and on the ratio of NADH/NAD+ in the cell. For example, in liver and heart, the ratio of NADH/NAD+ is lower than in exercising muscle. These tissues oxidize lactate (obtained from the blood) to pyruvate. In the liver, pyruvate is either converted to glucose by gluconeogenesis or oxidized in the TCA cycle. Heart muscle exclusively oxidizes lactate to CO2 and H20 via the citric acid cycle. 

Figure 3.2 Reductive citric acid cycle, ffi, ATP-citrate lyase 2-oxoglutarate ferredoxin oxidoreductase (2-oxoglutarate synthase)

Fig. 1.2 Intermediates of the citric acid cycle showing the relationship between glutamate and aspartate. Pyruvate dehydrogenase complex (1) citrate synthase (2) aconitase (3) isocitrate dehydrogenase (4) a-ketoglutarate dehydrogenase (5) succinyl-CoA synthetase (6) fumarate (7) fumarase dehydratase (8) malate dehydrogenase (9) and aspartate aminotransferase (10)...

Tables 4.10, 4.11, and 4.12 are the corresponding tables for pyruvate dehydrogenase, the citric acid cycle, the net reaction for the citric acid cycle, the net...

Table 4.10 Standard Transformed Reaction Gibbs Energies for Pyruvate Dehydrogenase, the Citric Acid Cycle, and Net Reactions at 298.15 K and 0.25 M Ionic Strength...

Problem 6.2 illustrates the use of equation 6.2-1 by applying it to four net reactions that represent the oxidation of glucose to carbon dioxide and water (1) the net reaction for glycolysis, (2) the net reaction catalyzed by the pyruvate dehydrogenase complex, (3) the net reaction for the citric acid cycle, and (4) the net reaction for oxidative phosphorylation. The v in equation 6.2-1 is the apparent stoichiometric number matrix for these four reactions. The net reaction is... 

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