Amino acids Krebs-citric acid cycle

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. 

Cobalt most often depresses the activity of enzyme including catalase, amino levulinic acid synthetase, and P-450, enzymes involved in cellular respiration. The Krebs citric acid cycle can be blocked by cobalt resulting in the inhibition of cellular energy production. Cobalt can replace zinc in a number of zinc-required enzymes like alcohol dehydrogenase. Cobalt can also enhance the kinetics of some enzymes such as heme oxidase in the liver. Cobalt interferes with and depresses iodine metabolism resulting in reduced thyroid activity. Reduced thyroid activity can lead to goiter. 

The citric acid cycle, also known as the TCA (tricarboxylic acid) cycle or Krebs cycle (after its discoverer in 1937), is used to oxidize the pyruvate formed during the glycolytic breakdown of glucose into C02 and H20. It also oxidizes acetyl CoA arising from fatty acid degradation (Topic K2), and amino acid degradation products (Topic M2). In addition, the cycle provides precursors for many biosynthetic pathways. 

These are the energy producers within the cell. They generate energy in the form of Adenosine Tri-Phosphate (ATP). Generally, the more energy a cell needs, the more mitochondria it contains. Site for Kreb s Citric Acid Cycle Electron transport system and Oxidative Phosphorylation Fatty acid oxidation Amino acid catabolism Interconversion of carbon skeletons. 

Urea cycle The formation of urea from amino group and ammonia. Also elucidated by H. A. Krebs, the discoverer of the citric-acid cycle. 

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). 

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. 

The citric acid cycle (also known as the tricarboxylic acid cycle, TCA cycle, Krebs cycle) oxidizes acetyl CoA in mitochondria. The cycle produces CO2, NADH and FADH2. The NADH and FADH2 enter oxidative phosphorylation, where they are oxidized to NAD+ and FAD, ready to be used in the citric acid cycle again. The citric acid cycle is also important in some biosynthetic processes such as lipid synthesis, amino acid synthesis, porphyrin synthesis and gluconeogenesis. 

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. 

It interferes with metabolic pathways of amino acids leading from glutamic acid to the citric acid (Krebs) cycle and urea. 

The interconnected cycles have been called the "Krebs bicycle." The pathways linking the citric acid and urea cycles are called the aspartate-argininosuccinate shunt these effectively link the fates of the amino groups and the carbon skeletons of amino acids. The interconnections are even more elaborate than the arrows suggest. For... 

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 a-keto acids formed by transamination of amino acids are further broken down in the citric acid (Krebs) cycle. This process yields energy, and the body s energy needs can be met with protein if sufficient carbohydrates or fats are not available. 

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 28-7. The metabolism of branched-chain amino acids and odd-chain fatty acids via propionyl-CoA. Propionyl-CoA is converted to D-methylmalonyl-CoA by propionyl-CoA carboxylase. D,L-Methylmalonyl-CoA racemase catalyzes the conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA. L-methyl malonyl-CoA mutase, an adenosyicobalamin-requiring enzyme, converts L-methylmalonyl-CoA to succinyl-CoA.TCA cycle is citric acid cycle or Kreb s cycle.

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. 

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.)... 

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. 

For example, as discussed in Chapter 7, Walden carried out studies involving the chiral dicarboxyUc acid, 2-hydroxybutane-l,4-dioic acid (2-hydroxysuccinic acid maUc acid), which, as noted there, he was able to obtain from the chiral dicarboxylic acid, 2-aminobutane-l,4-dioic acid (2-aminosuccinic acid aspartic acid). These dioic acids were readily available to Walden because they are naturally occurring. The first occurs as a species found in the citric acid cycle (also called the tricarboxylic acid cycle or the Krebs cycle ) and will be discussed in more detail in Chapter 11. The second, an amino acid, will be discussed with other members of the same family in Chapter 12. 

These products are absorbed across the wall of the small intestine into the blood and are transported to cells. Once in the cells, glucose and other monosaccharides, fatty acids, some amino acids, and glycerol enter the mitochondria and feed into a complex series of reactions called the citric acid cycle, or Krebs cycle. The citric acid cycle produces carbon dioxide and other molecules, such as NADH (not to be confused with NADPH) and ATP. This NADH and ATP then move through another set of reactions to produce more ATP and water. 

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