Acetyl-CoA in the citric acid cycle

There would be no effect on the concentrations of the glycolytic intermediates except, perhaps, an increase in the concentration of pyruvate. The cells would convert the lactate to pyruvate and use this as a precursor of acetyl-CoA in the citric acid cycle. If glucose or any other suitable carbohydrate is not available to the cell, then glycolysis cannot operate. 

The overall consumption of one molecule of acetyl-CoA in the citric acid cycle is an exergonic process AG° = —60 kJ mol-1. All but two of the individual reactions are exergonic. Step 2 (citrate— isocitrate) and step 8 (malate —>oxaloacetate) are endergonic (Fig. 12-3). 

Fig. 12-11 The distribution of the carbon atoms of acetyl-CoA in the citric acid cycle.

Pyruvate is converted to acetyl CoA with the formation of NADH, and fatty acids (attached to CoA) are also converted to acetyl CoA with formation of NADH and FADH. Oxidation of acetyl CoA in the citric acid cycle generates NADH and FADH2. Stage 2 Electrons from these reduced coenzymes are transferred via electron-transport complexes (blue boxes) to O2 concomitant with transport of H ions from the matrix to the intermembrane space, generating the proton-motive force. Electrons from NADH flow directly from complex I to complex III, bypassing complex II. 

What is the function of acetyl CoA in the citric acid cycle What is the function of oxaloacetate in the citric acid cycle GTP is formed in one step of the citric acid cycle. How is this GTP converted into ATP ... 

The function of acetyl CoA in the citric acid cycle is to bring the two-carbon remnant (acetyl group) of pyruvate from glycolysis and transfer it to oxaloacetate. In this way the acetyl group enters the citric acid cycle for the final stages of oxidation. 

In Chapter 17, we discussed the glycolytic pathway by which sugars are converted to pyruvate, which then enters the citric acid cycle. In Chapter 21, we will see how fatty acids are converted to acetyl-CoA we learned about the fate of acetyl-CoA in the citric acid cycle earlier in this chapter. Amino acids enter the cycle by various paths. We will discuss catabolic reactions of amino acids in Chapter 23. 

From seven cycles of p-oxidation 8 acetyl-CoA, 7 FADHg, and 7 NADH. From the processing of 8 acetyl-CoA in the citric acid cycle 8 FADH, 24 NADH, and 8 GTP. From reoxidation of all FADH and NADH 22.5 ATP from 15 FADHg, 77.5 ATP from 31 NADH. From 8 GTP 8 ATP. Subtotal 108 ATP. A 2-ATP equivalent was used in the activation step. Grand total 106 ATP. The grand total for stearic acid was 120 ATP. 

On page 478, the text shows that oxidation of acetyl CoA in the citric acid cycle yields 3 NADH, 1 FADH2, and 1 GTP, equivalent to 1 ATP, utilizing 2 water molecules. Thus, the 8 acetyl CoA molecules produced from palmitoyl CoA give 24 NADH, 8 FADH2, and 8 ATP equivalents, utilizing 16 water molecules. 

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative phosphorylation to produce COg and HgO represents stage 3 of catabolism. The end products of the citric acid cycle, COg and HgO, are the ultimate waste products of aerobic catabolism. As we shall see in Chapter 20, the oxidation of acetyl-CoA during stage 3 metabolism generates most of the energy produced by the cell. 

Step 1 of Figure 29.12 Addition to Oxaloacetate Acetyl CoA enters the citric acid cycle in step 1 by nucleophilic addition to the oxaloacetate carbonyl group, to give (S)-citryl CoA. The addition is an aldol reaction and is catalyzed by citrate synthase, as discussed in Section 26.11. (S)-Citryl CoA is then hydrolyzed to citrate by a typical nucleophilic acyl substitution reaction, catalyzed by the same citrate synthase enzyme. 

Acetyl-CoA enters the citric acid cycle (in the mitochondria of eukaryotes, the cytosol of prokaryotes) as citrate synthase catalyzes its condensation with oxaloacetate to form citrate. 

Acetyl-CoA enters the citric acid cycle (also called the Krebs cycle), which occurs in cell mitochondria. In the Krebs cycle, the acetyl group is oxidized to C02 and water, harvesting a substantial amount of energy. This complex cycle starts with the reaction of oxaloacetate with acetyl-CoA,... 

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... 

Approximately 2.5 molecules of ATP are generated when the respiratory chain oxidizes each of the 7 molecules of NADH, whereas 1.5 molecules of ATP are formed for each of the 7 molecules of FADH2 because their electrons enter the chain at the level of ubiquinol. Recall that the oxidation of acetyl CoA by the citric acid cycle yields 10 molecules of ATP. Hence, the number of ATP molecules formed in the oxidation of palmitoyl CoA is 10.5 from the 7 molecules of FADH2, 17.5 from the 7 molecules of NADH, and 80 from the 8 molecules of acetyl CoA, which gives a total of 108. The equivalent of 2 molecules of ATP is consumed in the activation of palmitate, in which ATP is split into AMP and 2 molecules of Pj. Thus, the complete oxidation of a molecule ofpalmitate yields 106 molecules of ATP. 

The acetyl CoA formed in fatty acid oxidation enters the citric acid cycle only if fat and carbohydrate degradation are appropriately balanced. The reason is that the entry of acetyl CoA into the citric acid cycle depends on the availability of oxaloacetate for the formation of citrate, but the concentration of oxaloacetate is lowered if carbohydrate is unavailable or improperly utilized. Recall that oxaloacetate is normally formed from pyruvate, the product of glycolysis, by pyruvate carboxylase (Section 16.3.1). This is the molecular basis of the adage that fats burn in the flame of carbohydrates. 

It is important to note that animals are unable to effect the net synthesis of glucose from fatty acids. Specifically, acetyl CoA cannot be converted into pyruvate or oxaloacetate in animals. The two carbon atoms of the acetyl group of acetyl CoA enter the citric acid cycle, but two carbon atoms leave the cycle in the decarboxylations catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase. Consequently, oxaloacetate is regenerated, but it is not formed de novo when the acetyl unit of acetyl CoA is oxidized by the citric acid cycle. In contrast, plants have two additional enzymes enabling them to convert the carbon atoms of acetyl CoA into oxaloacetate (Section 17.4.). 

The oxidation of acetyl CoA by the citric acid cycle plays a major role in providing energy in each of the following tissues EXCEPT... 

Fats and carbohydrates are metabolized down to carbon dioxide via an acetyl unit, CH3C=0, which is attached to a coenzyme, HSCoA, as a thioester called acetyl CoA. Acetyl CoA enters the citric acid cycle and eventually is converted to two molecules of carbon dioxide. The first step in the citric acid cycle is the aldol of acetyl CoA with oxaloacetate (Fig. 8.6). What is so elegant about this aldol is that the acidic and basic groups within the enzyme s active site provide a route that avoids any strongly acidic or basic intermediates. The enzyme accomplishes an aldol reaction at neutral pH, without an acidic protonated carbonyl or basic enolate intermediate via push-pull catalysis (Section 7.4.3). 

Oxidative degradation of acetyl coenzyme A (CoA) in the citric acid cycle gives a net yield of "which of the following chemicals ... 

---