Citric acid cycle pyruvate dehydrogenase reaction

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...

Recall What are the two most common inhibitors of steps of the citric acid cycle and the reaction catalyzed by 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. 

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) ... 

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... 

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. 

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... 

Net reaction for the pyruvate dehydrogenase reaction plus the citric acid cycle (10 reactions)... 

Net reaction for glycolysis, pyruvate dehydrogenase, and the citric acid cycle... 

Following this route under aerobic conditions, pyruvate is converted to acetyl CoA by the enzyme pyruvate dehydrogenase and the acetyl CoA then enters the citric acid cycle. The pyruvate dehydrogenase reaction is an oxidative decarboxylation (see Topic LI for details) ... 

In animals the acetyl CoA produced from fatty acid degradation cannot be converted into pyruvate or oxaloacetate. Although the two carbon atoms from acetyl CoA enter the citric acid cycle, they are both oxidized to C02 in the reactions catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase (see... 

Answer Anaplerotic reactions replenish intermediates in the citric acid cycle. Net synthesis of a-ketoglutarate from pyruvate occurs by the sequential actions of (1) pyruvate carboxylase (which makes extra molecules of oxaloacetate), (2) pyruvate dehydrogenase, and the citric acid cycle enzymes (3) citrate synthase, (4) aconitase, and (5) isocitrate dehydrogenase ... 

Answer Oxygen is the terminal electron acceptor in oxidative phosphorylation, and thus is needed to recycle NAD+ from NADH. NADH is produced in greatest quantities by the oxidative reactions of the citric acid cycle. In the absence of 02, the supply of NAD+ is depleted, and the accumulated NADH allosterically inhibits pyruvate dehydrogenase and cc-ketoglutarate... 

Answer Lactate and alanine are converted to pyruvate by their respective dehydrogenases, lactate dehydrogenase and alanine dehydrogenase, producing pyruvate and NADH + H+ and, in the case of alanine, NH. Complete oxidation of 1 mol of pyruvate to C02 and H20 produces 12.5 mol of ATP via the citric acid cycle and oxidative phosphorylation (see Table 16-1). In addition, the NADH from each dehydrogenase reaction produces 2.5 mol of ATP per mole of NADH reoxidized. Thus oxidation produces 15 mol of ATP per mole of lactate. Urea formation uses the equivalent of 4 mol of ATP per mole of urea formed (Fig. 18-10), or 2 mol of ATP per mol of NH4. Subtracting this value from the energy yield of alanine results in 13 mol of ATP per mole of alanine oxidized. 

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) ... 

The pyruvate dehydrogenase complex is not directly a part of the reactions that constitute the citric acid cycle. It is the link between glycolysis and the citric acid cycle, and its activity is controlled by the energy status of the mitochondria. 

The product of this reaction, oxaloacetate, can either enter the gluconeogenic pathway (Chap. 11) by way of malate or condense with acetyl-CoA to yield citrate. Pyruvate carboxylase is an allosteric enzyme, and it is activated by the heterotropic effector, acetyl-CoA. Thus, pyruvate in the mitochondria is the substrate for either pyruvate dehydrogenase or pyruvate carboxylase, the activities of which, in turn, are controlled by reactants associated with the citric acid cycle. The interplay among pyruvate dehydrogenase, pyruvate carboxylase, pyruvate, and the citric acid cycle is shown in Fig. 12-9. 

The cycle oxidizes acetyl-CoA, and to perform this task, it must convert acetyl-CoA to citrate. For this to be achieved, oxaloacetate must be available. If the removal of intermediates results in a decrease in the amount of oxaloacetate for this purpose, acetyl-CoA cannot be removed and will accumulate. This will inhibit the pyruvate dehydrogenase complex and activate pyruvate carboxylase, leading to the conversion of pyruvate to oxaloacetate. This product is now available to condense with the acetyl-CoA to produce citrate, which will restore the status quo. Reactions like that of pyruvate carboxylase that provide molecules for the replacement of intermediates of the citric acid cycle are known as anaplerotic reactions (Greek, meaning to fill up ana = up + plerotikos from pleroun = to make full ). 

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