Citric acid cycle overall pathway

The two transamination steps in the pathways may be linked, as indicated in Fig. 17-5, to form a complete cycle that parallels the citric acid cycle but in which 2-oxoglutarate is oxidized to succinate via glutamate and y-aminobutyrate. No thiamin diphosphate is required, but 2-oxoglutarate is reductively aminated to glutamate. The cycle is sometimes called the y-aminobutyrate shunt, and it plays a significant role in the overall oxidative processes of brain tissue. 

The urea cycle Urea is synthesized in the liver by the urea cycle. It is then secreted into the bloodstream and taken up by the kidneys for excretion in the urine. The urea cycle was the first cyclic metabolic pathway to be discovered by Hans Krebs and Kurt Henseleit in 1932,5 years before Krebs discovered the citric acid cycle (see Topic LI). The overall reaction of the pathway is ... 

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) ... 

Figure 19.10 shows schematically the various catabolic pathways that feed into the citric acid cycle. The catabolic reactions occur in the cytosol the citric acid cycle takes place in mitochondria. Many of the end products of catabolism cross the mitochondrial membrane and then participate in the citric acid cycle. This figure also shows the outline of pathways by which amino acids are converted to components of the citric acid cycle. Be sure to notice that sugars, fatty acids, and amino acids are all included in this overall catabolic scheme. Just as all roads lead to Rome, all pathways lead to the citric acid cycle. 

The overall pathway has a AG° of —77.7 y mol . During the course of the cycle, starting from pyruvate, four NADH molecules and one FADHg are produced. Between the GTP formed directly and the reoxidation of the reduced electron carriers by the electron transport chain, the citric acid cycle produces 25 ATP. Gontrol of the citric acid cycle is exercised at three points. 

Although the citric acid cycle is generally regarded as a pathway for the oxidation of four- and five-carbon compounds arising from amino acids, such as fumarate, oxaloacetate, OC-ketoglutarate and succinate (see Figure 5.20), it does not, alone, permit complete oxidation of these compounds. Four-carbon intermediates are not overall consumed in the cycle, as oxaloacetate is reformed. Addition of four- and five-carbon intermediates will increase the rate of cycle activity (subject to control by the requirement for ATP) only until the pool of intermediates is saturated. 

The overall condition of Max s metabolism is determined by the concentration of glucose and several enzymes. Metabolism includes all of the chemical reactions in the body involving the breakdown of molecules to produce energy or the synthesis of complex molecules for cellular growth. These reactions frequently occur in a series and require multiple enzymes. The oxidation of glucose involves several of these metabolic pathways including glycolysis, the citric acid cycle, and electron transport. 

---