Carbohydrate Krebs-citric acid cycle

The conversion of fumaric acid to malic acid is an important biological hydration reaction. It is one of a cycle of reactions (Krebs citric acid cycle) involved in the metabolic combustion of fuels (amino acids and carbohydrates) to C02 and H20 in a living cell. 

The Krebs-citric acid cycle is the final common pathway for the oxidation of fuel molecules amino acids, fatty acids and carbohydrates. Most fuel molecules enter the cycle as a breakdown product, acetyl coenzyme A (acetyl CoA), which reacts with oxaloacetate (a four-carbon compound) to produce citrate (a six-carbon compound), which is then converted in a series of enzyme-catalysed steps back to oxaloacetate. In the process, two molecules of carbon dioxide and four energy-rich molecules are given off, and these latter are the precursors of the energy-rich molecule ATP, which is subsequently formed and which acts as the fuel source for all aerobic organisms. 

Another important concept, recently demonstrated, is the interrelationship of protein, fat, and carbohydrate oxidative mechanisms and the final common pathway through the Krebs citric acid cycle (Chapter 16). 

Physiological Role of Citric Acid. Citric acid occurs ia the terminal oxidative metabolic system of virtually all organisms. This oxidative metabohc system (Fig. 2), variously called the Krebs cycle (for its discoverer, H. A. Krebs), the tricarboxyUc acid cycle, or the citric acid cycle, is a metaboHc cycle involving the conversion of carbohydrates, fats, or proteins to carbon dioxide and water. This cycle releases energy necessary for an organism s growth, movement, luminescence, chemosynthesis, and reproduction. The cycle also provides the carbon-containing materials from which cells synthesize amino acids and fats. Many yeasts, molds, and bacteria conduct the citric acid cycle, and can be selected for thek abiUty to maximize citric acid production in the process. This is the basis for the efficient commercial fermentation processes used today to produce citric acid. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs tycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

The enzyme isocitrate dehydrogenase is one of the enzymes of the Krebs or citric acid cycle, a major feature in carbohydrate metabolism (see Section 15.3). This enzyme has two functions, the major one being the dehydrogenation (oxidation) of the secondary alcohol group in isocitric acid to a ketone, forming oxalosuccinic acid. This requires the cofactor NAD+ (see Section 11.2). For convenience, we are showing non-ionized acids here, e.g. isocitric acid, rather than anions, e.g. isocitrate. 

The citric acid cycle (Krebs cycle, TCA cycle) is a nearly universal central catabolic pathway in which compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to C02, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to 02 and the energy of electron flow is trapped as ATP. 

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 citric acid cycle is sometimes called the Krebs cycle, in honor of its discoverer. Sir Hans Krebs. It is the final stage of the breakdown of carbohydrates, fats, and amino acids released from dietary proteins (Figure 22.5). 

Krebs found that the pivotal mechanism of cell metabolism was a cycle. The cycle starts with glycolysis, which produces acetyl coenzyme A (acetyl CoA) fiom 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 tri-carhoxyhc 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.)... 

KREBS CYCLE A series of chemical reactions in the body that form part of the pathway by which cells break down carbohydrates, fats, and proteins for energy. Also called the citric acid cycle. 

The citric acid cycle, also known as the tricarboxylic acid cycle or the Krebs cycle, is the final oxidative pathway for carbohydrates, lipids, and amino acids. It is also a source of precursors for biosynthesis. The authors begin Chapter 17 with a detailed discussion of the reaction mechanisms of the pyruvate dehydrogenase complex, followed by a description of the reactions of the citric acid cycle. This description includes details of mechanism and stereospecificity of some of the reactions, and homologies of the enzymes to other proteins. In the following sections, they describe the stoichiometry of the pathway including the energy yield (ATP and GTP) and then describe control mechanisms. They conclude the chapter with a summary of the biosynthetic roles of the citric acid cycle and its relationship to the glyoxylate cycle found in bacteria and plants. 

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. 

Although the Krebs cycle is usually considered as part of carbohydrate metabolism, it should be emphasized that amino acids (final products of protein catabolism), acetyl coenzyme A, and acetoacetic acid (final product of fat catabolism) are all oxidized through the citric acid cycle. The Krebs cycle is thus a system capable of oxidizing the final products of carbohydrates, proteins, and fats. 

In the period between 1935 and 1950 there was discovered a principal way in which the oxidation of carbohydrates to water and carbon dioxide is carried out with production of a number of high-energy molecules for each molecule of carbon dioxide formed. This biochemical mechanism is called the citric acid cycle or the Krehs cycle. It was in large part formu- lated by 1943 by the British biochemist Hans Adolf Krebs (born 1900), after Albert Szent-Gyorgyi in 1935 had discovered that enzymes from muscle could catalyze the oxidation of dicarboxylic four-carbon acids (succinic, fumaric, malic, and oxaloacetic acid). 

This oxygen-requiring (aerobic) metabolic process, which is also known as the Krebs cycle, is the means by which metabolic products of fats, carbohydrates, and protein are converted to water and carbon dioxide, plus energy. The citric acid cycle operates in the mitochondria of cells, where the appropriate enzymes are located. 

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