Carbohydrate metabolism Krebs tricarboxylic acid cycle

Glutfflnic acid is fonned in most organisms from ammonia and a-ketoglutaric acid. a-Ketoglutaric acid is one of the intennediates in the tricarboxylic acid cycle (also called the Krebs cycle) and arises via metabolic breakdown of food sources carbohydrates, fats, and proteins. 

We will now draw attention to the Krebs cycle otherwise called the tricarboxylic acid cycle (fig. 17). It is now known that carbohydrate metabolism and fatty acid metabolism as well as acetate proceed via changes indicated in the cycle. The essential... 

TCA cycle. (tricarboxylic acid cycle Krebs cycle citric acid cycle). A series of enzymatic reactions occurring in living cells of aerobic organisms, the net result of which is the conversion of pyruvic acid, formed by anaerobic metabolism of carbohydrates, into carbon dioxide and water. The metabolic intermediates are degraded by a combination of decarboxylation and dehydrogenation. It is the major terminal pathway of oxidation in animal, bacterial, and plant cells. Recent research indicates that the TCA cycle may have predated life on earth and may have provided the pathway for formation of amino acids. 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

Krebs found that the pivotal mechanism of cell metabolism was a cycle. The cycle starts with glycolysis, which produces acetyl coenzyme A (acetyl CoA) from food molecules—carbohydrates, fats, and certain amino acids. The acetyl CoA reacts with oxaloacetate to form citric acid. The citric acid then goes through seven reactions that reconvert it back to oxaloacetate, and the cycle repeats. There is a net gain of twelve molecules of ATP per cycle. Not only does this cycle (known as the Krebs cycle, and also as the tricarboxylic acid cycle and the citric acid cycle) generate the chemical energy to run the cell, it is also a central component of the syntheses of other biomolecules. 

The sequence of events known as the Krebs cycle is indeed a cycle ox-aloacetate is both the first reactant and the final product of the metabolic pathway (creating a loop). Because the Krebs cycle is responsible for the ultimate oxidation of metabolic intermediates produced during the metabolism of fats, proteins, and carbohydrates, it is the central mechanism for metabolism in the cell. In the first reaction of the cycle, acetyl CoA condenses with oxaloacetate to form citric acid. Acetyl CoA utilized in this way by the cycle has been produced either via the oxidation of fatty acids, the breakdown of certain amino acids, or the oxidative decarboxylation of pyruvate (a product of glycolysis). The citric acid produced by the condensation of acetyl CoA and oxaloacetate is a tricarboxylic acid containing three car-boxylate groups. (Hence, the Krebs cycle is also referred to as the citric acid cycle or tricarboxyfic acid cycle.)... 

Under aerobic conditions, the central metabolic pathway for the oxidation of the carbon skeletons not only of carbohydrates, but also of fatty acids and amino acids, to carbon dioxide is the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle and Krebs cycle. The last-mentioned name is in honor of Sir Adolph Krebs, the biochemist who first proposed the cyclic nature of this pathway in 1937. 

An organic 3-carbon acid that is a key intermediate in carbohydrate, fat, and protein metabolism. It can participate in several metabolic pathways in the E)ody. These pathways include (1) complete oxidation to water and carbon dioxide in the tricarboxylic acid (Krebs) cycle, (2) formation of fatty acid, (3) reversible conversion to lactic acid, (4) conversion to the amino acid alanine, and (5) formation of glucose by reversal of the enzymatic sequence which normally breafe down glucose. 

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