Citric acid cycle electron-transport chain

Now we can calculate the energy yield for the entire catabolic pathway (citric acid cycle, electron transport chain, and oxidative phosphorylation combined). According to Section 23.5, every acetyl CoA entering the citric add cycle produces 3 NADH and 1 FADH2 plus 1 GTP, which is equivalent in energy to 1 ATP. Thus, 10 ATP molecules are formed per molecule of acetyl CoA catabolized. 

Three very important coenzymes are involved in catabolism coenzyme A, NAD, and FAD. Coenzyme A binds to the two-carbon fragments produced in Stage II to form acetyl CoA, the direct fuel of the citric acid cycle. NAD and FAD are the oxidizing agents that participate in the oxidation reactions of the citric acid cycle. They transport hydrogen atoms and electrons from the citric acid cycle to the electron transport chain. 

In eukaryotes, oxidative phosphorylation occurs in mitochondria, while photophosphorylation occurs in chloroplasts to produce ATP. Oxidative phosphorylation involves the reduction of O2 to H2O with electrons donated by NADH and FADH2 in all aerobic organisms. After, carbon fuels (nutrients) are oxidized in the citric acid cycle, electrons with electron-motive force is converted into a proton-motive force. Photophosphorylation involves the oxidation of H2O to O2, with NADP as electron acceptor. Therefore, the oxidation and the phosphorylation of ADP are coupled by a proton gradient across the membrane. In both organelles, mitochondria and chloroplast electron transport chains pump protons across a membrane from a low proton concentration region to one of high concentration. The protons flow back from intermembrane to the matrix in mitochondria, and from thylakoid to stroma in chloroplast through ATP synthase to drive the synthesis of adenosine triphosphate. Therefore, the adenosine triphosphate is produced within the matrix of mitochondria and within the stroma of chloroplast. 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

As its name implies, the citric acid cycle is a closed loop of reactions in which the product of the hnal step (oxaloacetate) is a reactant in the first step. The intermediates are constantly regenerated and flow continuously through the cycle, which operates as long as the oxidizing coenzymes NAD+ and FAD are available. To meet this condition, the reduced coenzymes NADH and FADH2 must be reoxidized via the electron-transport chain, which in turn relies on oxygen as the ultimate electron acceptor. Thus, the cycle is dependent on the availability of oxygen and on the operation of the electron-transport chain. 

The citric acid cycle, also called the Krebs cycle or the tricarboxylic add (TCA) cyde, is in the mitochondria. Although oxygen is not directly required in the cyde, the pathway will not occur anaerobically because NADH and FADH will accumulate if oxygen is not available for the electron transport chain. 

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. 

As noted earlier, coenzymes are frequently altered structurally in the course of an enzymatic reaction. However, they are usually reconverted to their original structure in a subsequent reaction, as opposed to being further metabolized. One turn of the citric acid cycle converts NAD+ into NADH, FAD into FADH2, and acetyl-SCoA into CoASH. Coenzyme A is consumed in the metabolism of pyruvate (see below) but regenerated in the citric acid cycle. Both NADH and FADH2 are reconverted into NAD+ and FAD by the electron transport chain. 

In this reaction, pyruvic acid is oxidized to carbon dioxide with formation of acetyl-SCoA and NAD+ is reduced to NADH. As noted in chapter 15, this reaction requires the participation of thiamine pyrophosphate as coenzyme. Here too the NADH formed is converted back to NAD+ by the electron transport chain. As noted above, the acetyl-SCoA is consumed by the citric acid cycle and CoASH is regenerated. 

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. 

NO also has cytotoxic effects when synthesized in large quantities, eg, by activated macrophages. For example, NO inhibits metalloproteins involved in cellular respiration, such as the citric acid cycle enzyme aconitase and the electron transport chain protein cytochrome oxidase. Inhibition of the heme-containing cytochrome P450 enzymes by NO is a major pathogenic mechanism in inflammatory liver disease. 

The study of electron transport chains and of oxidative phosphorylation began in earnest after Kennedy and Lehninger) in 1949, showed that mitochondria were the site not only of ATP synthesis but also of the operation of the citric acid cycle and fatty acid oxidation pathways. By 1959, Chance had introduced elegant new techniques of spectrophotometry that led to formulation of the electron... 

Because of its critical role in ATP production, a homozygotic defect in a gene for a protein involved in glycolysis, the citric acid cycle, or the electron transport chain probably leads to the death of the cell(s) soon after fertilization. 

Fats, carbohydrates, and proteins are metabolized in the body to yield acetyl CoA, which is further degraded in the citric acid cycle to yield two molecules of CO2 plus a large amount of energy. The energy output of the various steps in the citric acid cycle is coupled to the electron-transport chain, a series of enzyme-catalyzed reactions whose ultimate purpose is to synthesize adenosine triphosphate (ATP). 

Mitochondria arc membranous organelles (Fig. 1-9) of great importance in the energy metabolism of the cell they are the source of most of the ATP (Chap. 14) and the site of many metabolic reactions. Specifically, they contain the enzymes of the citric acid cycle (Chap. 12) and the electron-transport chain (Chap. 14), which includes the main oxygen-utilizing reaction of the cell. A mammalian liver cell contains about 1.000 of these organelles about 20 percent of the cytoplasmic volume is mitochondrial. 

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