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The citric acid cycle has been described as "the hub of the metabolic wheel". Discuss the roles of the citric acid cycle in the oxidation of various fuel molecules and the provision of carbon skeletons for biosynthesis

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Introduction

The citric acid cycle has been described as "the hub of the metabolic wheel". Discuss the roles of the citric acid cycle in the oxidation of various fuel molecules and the provision of carbon skeletons for biosynthesis The citric acid cycle is one of three stages of cellular respiration. The others are glycolysis and electron transport or oxidative phosphorylation. Glycolysis breaks one glucose molecule, producing six ATP (adenosine triphosphate) molecules, a fundamental energy provider in cells. Pyruvate is used to make acetyl-CoA, the starting product for the citric acid cycle. The reaction involves oxidation and decarboxylation of a 3 carbon pyruvic acid to form 2 carbon acetyl Co-A. It occurs in the cell cytoplasm and requires the presence of co-enzyme-A and NAD. It is catalyzed by complex enzymes. In this process, carbon dioxide is released and the reduced co-enzyme NADH2 is formed. 2 Pyruvic acid + 2Co-A + 2NAD --> 2 Acetyl Co-A + 2CO2 + 2NADH2 The 2-C acetyl Co-A formed in the cytoplasm then enters the mitochondria and takes part in the citric acid cycle reactions, thus, acetyl Co-A is the connecting link between glycolysis (in the cytoplasm) and citric acid cycle (in mitochondria). ...read more.

Middle

and decarboxylation to form 4 carbon succinyl Co-A. The reaction is highly complicated and takes place in the presence of Co-A and NAD. NADH2 is formed and carbon dioxide is released. 4 carbon Succinyl Co-A is hydrolyzed to succinic acid (4 carbon) in the next step. One molecule of H2O is used and Co-A is regenerated. The reaction is exergonic. Energy released is used for the formation of GTP (guanosine triphosphate) from GDP and inorganic phosphate. Subsequently, ATP is formed when GTP reacts with ADP GTP + ADP ? ATP + GDP (Thus, there is the direct formation of one ATP when a 5 carbon acid is converted to a 4 carbon acid.) In the next step, 4-C Succinic acid is oxidized (by removal of hydrogen) to 4 carbon fumaric acid in the presence of co-enzyme FAD (flavin adenine dinucleotide). A reduced FADH2 is formed. Fumaric acid (4 carbon) is converted to another 4 carbon acid, malic acid, by the addition of H2O. In the final step of the citric acid cycle, 4 carbon malic acid is oxidized (by removal of hydrogen) ...read more.

Conclusion

Depletion of oxaloacetic acid under these conditions is prevented by its net synthesis in the pyruvate carboxylase reaction. Pyruvate carboxylase provided oxaloacetic acid in cells actively synthesizing carbohydrate. Most of the oxaloacetic acid destined for gluconeogenesis (in the cytoplasm) leaves the mitochondrion as malate. In the cytoplasm, malate is reconverted to oxaloacetic acid + NADH and then to PEP. This indirect "shuttle" route is required because neither NAD+ nor NADH can be transported across the mitochondrial membranes. The pathway for fatty acid synthesis in the cytoplasm requires a similar shuttle system involving transport of malate and citrate out of the mitochondrion. If the available (and storage) supply of carbohydrate is sufficient, the malate is converted to pyruvate + CO2 + NADPH in the malic enzyme-catalyzed reaction. This variant of the malate shuttle is significant because the NADPH is used as reducing agent in the fatty acid synthesis pathway. There are several other, similar feed-in reactions, enabling cycle intermediates to be tapped off for anabolic purposes. The 'feed-in' reactions are called anaplerotic (or replenishing) reactions. Because of this capacity for anabolic activity, the citric acid cycle is sometimes referred to as being amphibolic, having both catabolic and anabolic activity. ...read more.

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