Tricarboxylic acid cycle acetyl coenzyme

The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP. 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

The net outcome is that each rotation of the tricarboxylic acid cycle converts one acetyl residue and two molecules of H2O into two molecules of CO2. At the same time, one GTP, three NADH+H"" and one reduced ubiquinone (QH2) are produced. By oxidative phosphorylation (see p. 122), the cell obtains around nine molecules of ATP from these reduced coenzymes (see p. 146). Together with the directly formed GTP, this yields a total of 10 ATP per acetyl group. 

The most important process in the degradation of fatty acids is p-oxidation—a metabolic pathway in the mitochondrial matrix (see p. 164). initially, the fatty acids in the cytoplasm are activated by binding to coenzyme A into acyl CoA [3]. Then, with the help of a transport system (the carnitine shuttle [4] see p. 164), the activated fatty acids enter the mitochondrial matrix, where they are broken down into acetyl CoA. The resulting acetyl residues can be oxidized to CO2 in the tricarboxylic acid cycle, producing reduced... 

Reactions of the TCA cycle Enzyme that oxidatively decarboxylates pyruvate, its coenzymes, activators, and inhibitors REACTIONS OF THE TRICARBOXYLIC ACID CYCLE (p. 107) Pyruvate is oxidatively decarboxylated by pyruvate dehydrogenase complex producing acetyl CoA, which is the major fuel for the tricarboxylic acid cycle (TCA cycle). The irreversible set of reactions catalyzed by this enzyme complex requires five coenzymes thiamine pyrophosphate, lipoic acid, coenzyme A (which contains the vitamin pantothenic acid), FAD, and NAD. The reaction is activated by NAD, coenzyme A, and pyruvate, and inhibited by ATP, acetyl CoA, and NADH. 

Acetyl-CoA. Acetyl-coenzyme A, a high-energy ester of acetic acid that is important both in the tricarboxylic acid cycle and in fatty acid biosynthesis. 

In addition, most peroxisomes catalyze the oxidation of long-chain fatty acids to acetyl CoA (coenzyme A), which can be transported through the cytosol to mitochondria for use in the tricarboxylic acid cycle. 

Practically all tissues can degrade glucose by the process of glycolysis. In this pathway, glucose is converted to two molecules of pyruvate, with the production of two ATP molecules. Two molecules of NAD+ are also reduced to NADH. Pyruvate may proceed in at least two directions toward the formation of lactate, in which case the glycolysis is anaerobic, or toward the formation of acetyl coenzyme A (acetyl-CoA) and oxidation via the Krebs cycle (also called the tricarboxylic acid cycle). In the former case, pyruvate is reduced by NADH and... 

C-sodium acetate is produced by the reaction of the Grignard reagent, methylmagnesium bromide in diethyl ether, with cyclotron-produced nC-carbon dioxide at -15°C (Oberdorfer et al, 1996). After reaction, the product is allowed to react with O-phthaloyl dichloride to produce nC-acetyl chloride, which is then hydrolyzed to 11C-acetate with saline. The solution is filtered through a 0.22-pm membrane filter. 11C-acetate has been found to be stable at pH between 4.5 and 8.5 for up to 2 h at room temperature. The overall yield is about 10-50%. It is used for the measurement of oxygen consumption (oxidative metabolism) in the heart, since acetyl CoA synthetase converts 11C-acetate to acetyl coenzyme A after myocardial uptake, which is metabolized to 11C-C02 in the tricarboxylic acid cycle. 

Fig. 3-10 The biochemical pathway of the tricarboxylic acid cycle (TCA cycle). Pyruvate, generated from glycolysis (Fig. 3-8), enters the cycle as acetyl-CoA (acetyl-coenzyme A), and is then degraded through a series of reactions to a 4-carbon compound, oxaloacetate. The energy resulting from the reactions is stored as ATP, which is produced through electron transport and oxidative phosphorylation (see Fig. 3-11).

Figure 16. A schematic view of the flow of carbon within the tricarboxylic-acid cycle. The labels m, c, and b designate respectively carbon from the methyl and carboxyl positions of acetyl-CoA and from bicarbonate used to produce oxaloacetate from phosphoenolpymvate. Inputs and outputs of water, of redox cofactors (NAD, etc.), and of coenzymes (CoASH) have been omitted in order to focus on the carbon skeletons. The amination of a-ketoglutarate in order to produce glu is the principal means of importing N for use in the amino-acid pool. The process involves multiple steps, including a reduction (indicated by addition of [H]) and is represented here only schematically. The boldface T indicates transamination, an example of which is shown in equation 21. The circled P represents a phosphate group, POs. Pj represents inorganic phosphate, HP04 .

The metabolic intermediate (e.g., pyrnvate) nndergoes complete oxidation to CO2, throngh the pathway referred to as tricarboxylic acid cycle (TCA cycle). The following reactions are involved in TCA cycle. The hrst step involves conversion of pyrnvate to acetyl-CoA throngh decarboxylation and prodnction of NADH. The acetyl-CoA (2 carbon) combines with the fonr-carbon componnd oxalacetate, leading to the formation of citric acid (6 carbon). The TCA cycle is also referred to as citric acid cycle. A series of reactions inclnding dehydration, decarboxylation, and oxidation are involved in the conversion of citric acid to carbon dioxide. The electrons released are transferred to enzymes containing the coenzyme NAD+. 

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. 

In normal liver, only relatively small amounts of ketone bodies are formed. Their concentration in the blood is 0.5-D.8 mg per 100 ml plasma. The acetoacetate produced by this physiological K. is degraded in the peripheral musculature. Coenzyme A from succi-nyl-CoA is transferred to the acetoacetate by aceto-acetate succinyl-CoA transferase. Direct activation of acetoacetate by coenzyme A and ATP can also occur (Fig, 2). The acetoacetyl-CoA produced in either case is thioclastically cleaved into two molecules of acetyl-CoA, consuming a CoA molecule in the process. In carbohydrate deficiency (starvation, ketone-mia in ruminants), or deficient carbohydrate utilization (diabetes mellitus), K. is greatly increased. The cause of this pathological K. is a disturbance of the equilibrium between the degradation of fatty acids to acetyl-CoA and its utilization in the tricarboxylic acid cycle. The several-fold increase in the oxidation of the fatty acids leads under these conditions to an increase in the intracellular acetyl-CoA concentration. This leads to the condensation of 2 molecules of... 

The hydrogen is removed via the normal NAD" pathway. The acetyl-coenzyme A produced is then oxidised to carbon dioxide and water via the tricarboxylic acid cycle (also known as the Kreb s or citric acid cycle), as shown in Fig. 9.5. 

Glycolysis takes place in the cell cytoplasm, whereas the decarboxylation of pyruvate and the subsequent oxidation of acetyl-coenzyme A via the tricarboxylic acid cycle take place in the mitochondrial matrix. Under anaerobic conditions, oxygen is not available for the oxidation of reduced NAD by oxidative phosphorylation, in order to allow the release of a small amount of energy by continuing the breakdown of glucose to pyruvate, reduced NAD must be converted to the oxidised form, if not, step 7 of Fig. 9.4 will not take place and energy production will be blocked. Oxidation of reduced NAD may be achieved under such conditions by the formation of lactate from pyruvate in the presence of lactate dehydrogenase ... 

The acetyl-coenzyme A is metabolised via the tricarboxylic acid cycle. We may calculate the energy released from butyrate by the synthetase pathway as follows ... 

Building blocks for cholesterol include acetate, acetyl-CoA and acetoacetyl CoA. There are many sources of these metabolites in the body including the tricarboxylic acid cycle (TCA) but also microbial-derived acetate, the main end-product of carbohydrate fermentation in the colon which is converted into acetyl-CoA by acetyl coenzyme A synthetase 1 (AceCSl) in the cytosol. Acetate may also be taken up by mitochondria and converted into acetyl-coA by AceCS2 for respiration through the TCA, especially under ketogenic or fasting conditions. In... 

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