Krebs tricarboxylic acid cycle

Robinson, J.B. Srere, P.A. (1985). Organization of Krebs tricarboxylic acid cycle enzymes in mitochondria. J. Biol. Chem. 260, 10800-10805. 

Figure 10-6 Reactions of the citric acid cycle (Krebs tricarboxylic acid cycle). Asterisks designate positions of isotopic label from entrance of carboxyl-labeled acetate into the cycle. Note that it is not the two carbon atoms from acetyl-CoA that are immediately removed as C02 but two atoms from oxaloacetate. Only after several turns of the cycle are the carbon atoms of the acetyl-CoA completely converted to C02. Nevertheless, the cycle can properly be regarded as a mechanism of oxidation of acetyl groups to C02. Green daggers (+) designate the position of 2H introduced into malate as 2H from the medium. FADS designates covalently bound 8-histidyl-FAD (see Chapter 15).

BOX 10-B DISCOVERY OF THE CITRIC ACID CYCLE (KREBS TRICARBOXYLIC ACID CYCLE)... 

To obtain citric acid as the metabolic product again requires interference with the normal Krebs tricarboxylic acid cycle in such a way that citric acid metabolism is blocked. Usually this is achieved by careful regulation of concentrations of trace metals available as coenzymes to the various enzyme pathways used by A. niger, so that some of these are rendered ineffective (are blocked). 

The mechanism of MCA toxicity seems to be via inhibition of the enzyme pyruvate dehydrogenase this inhibition blocks the Krebs (tricarboxylic acid) cycle and disrupts the cell s energy supply. Almost immediately, the cell finds itself without energy. Ketoglutarate dehydrogenase activity is also reduced, which causes lactic acidosis. The MCA also damages the blood-brain barrier, probably through the formation of vascular endothelial microlesions. 

Under aerobic conditions, the main metabolic route is oxidation to carbon dioxide and water (respiration). In order to accomplish this, the pyruvic acid from the glycolysis process enters another series of reactions known as the Krebs Tricarboxylic Acid cycle (Citric Acid cycle) (Figure 11.21), where overall breakdown occurs with elimination of CO2 and H2O [9]. 

The Embden-Meyerhof pathway with the Krebs tricarboxylic acid cycle is the most universal glucose oxidation system found in nature. It is, however, by no means the only one. Many variations of the Krebs cycle are known to exist in different organisms and species, although phosphate esters are involved in all of these at some stage or other. 

Glycolysis proceeds to the pyruvic acid level in the cytoplasm, and then the pyruvic acid or the 2-carbon substances produced from it must come into contact with, or enter into, the mitochondria for the next stage of respiration to take place. The 2-carbon substances are drawn into the Krebs tricarboxylic acid cycle within or on the surface of the mitochondria, become condensed with oxaloacetic acid to form citric acid, and then pass round the cycle giving off (for each molecule of pyruvic acid entering the system) three molecules of carbon dioxide and five pairs of hydrogen atoms. These pairs of hydrogen atoms are swept away from the Krebs cycle and, through the aid of coenzyme I, coenzyme II, and cytochrome c form water and simultaneously reduce the cytochrome which is reoxidized by cytochrome oxidase. It should be stressed that the whole of this process, from pyruvic acid to the production of CO2 and water, can be carried out by mitochondria, which appear to have sufficient of all the enzymes necessary for... 

There is a number of similar procedures starting fntm olefinic diols which by reaction with dinitrogen tetraoxide give citric acid. Sargsyan et al. [11] presented a short account of all known until 1989 synthetic preparations of citric acid. Their paper is based mainly on the patent literature and shows that with an exception of old classical methods, most of other ways to obtain citric acid is characterized by relatively low yield. Evidently, in the context of the Krebs tricarboxylic acid cycle, there is a large number of investigations dealing with enzymatic synthesis of citric acid by condensation of acetate and oxalacetate [12-20]. 

Thermoanalytical characteristics of citric acid were also studied by Trask-Morrell and Kottes Andrews [74] in the 60-600 °C temperature range. They found that anhydrous citric acid melted at 152-154 °C and then was decomposed at 228-242 °C. The weight loss of about 96 % of sample size was observed (in an apparent single peak), and at 575 °C, the residue of sample was very small. Thermal analysis of binary systems included in the Krebs tricarboxylic acids cycle was performed by UsoTtseva et al. [75-78]. They investigated systems of fumaric acid, malic acid, succinic acid, cis-aconitic acid and a-ketoglutaric acid with citric acid. They... 

Usol tseva VA, Pobedinskaya AI, Kobenina NM (1970) Thermographic analysis of Krebs tricarboxylic acid cycle intermediates and their systems. Izv Vyss Ucheb Zaved Khimiya... 

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