Krebs tricarboxylic acid cycle acids

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

Thiamine is required by the body as the pyrophosphate (TPP) in two general types of reaction, the oxidative decarboxylation of a keto acids catalyzed by dehydrogenase complexes and the formation of a-ketols (ketoses) as catalyzed by transketolase, and as the triphosphate (TTP) within the nervous system. TPP functions as the Mg -coordinated coenzyme for so-called active aldehyde transfers in mul-tienzyme dehydrogenase complexes that affect decarboxyia-tive conversion of a-keto (2 oxo) acids to acyl-coenzyme A (acyl-CoA) derivatives, such as pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. These are often localized in the mitochondria, where efficient use in the Krebs tricarboxylic acid (citric acid) cycle follows. 

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... 

Glutamic acid is formed m most organisms from ammonia and a ketoglutaric acid a Ketoglutaric acid is one of the intermediates m the tricarboxylic acid cycle (also called the Krebs cycle) and arises via metabolic breakdown of food sources carbohy drates fats and proteins... 

In addition to its presence in fmits, S(—)-malic acid has been found in cultures of a variety of microorganisms including the aspergiUi, yeasts, species of Sekrotinia, and Penicillium brevicompactum. Yields of levorotatory malic acid as high as 74% of theoretical have been reported. Iron, manganese, chromium, or aluminum ions reportedly enhance malic acid production. S(—)-Mahc acid is involved in two respiratory metaboHc cycles the Krebs tricarboxylic acid... 

Krebs, H. A., 1970. The hi.story of the tricarboxylic acid cycle. Perspectives in Biology and Medicine 14 154—170. 

The citrate cycle is the final common pathway for the oxidation of acetyl-CoA derived from the metabolism of pyruvate, fatty acids, ketone bodies, and amino acids (Krebs, 1943 Greville, 1968). This is sometimes known as the Krebs or tricarboxylic acid cycle. Acetyl-CoA combines with oxaloacetate to form citrate which then undergoes a series of reactions involving the loss of two molecules of CO2 and four dehydrogenation steps. These reactions complete the cycle by regenerating oxaloacetate which can react with another molecule of acetyl-CoA (Figure 4). 

Wachtcrshauser s prime candidate for a carbon-fixing process driven by pyrite formation is the reductive citrate cycle (RCC) mentioned above. Expressed simply, the RCC is the reversal of the normal Krebs cycle (tricarboxylic acid cycle TCA cycle), which is referred to as the turntable of metabolism because of its vital importance for metabolism in living cells. The Krebs cycle, in simplified form, can be summarized as follows ... 

Fig. 6.6 The modem version of the tricarboxylic acid cycle (Kreb s cycle).

The tricarboxylic acid cycle is also known as the Krebs cycle or the citric acid cycle. Why give something so central to life only one name ... 

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... 

The consequent interpretation, accepted by Krebs in his review of the tricarboxylic acid cycle in 1943, was therefore that citric acid could not be an intermediate on the main path of the cycle, and that the product of the condensation between oxaloacetate and acetyl CoA would have to be isocitrate, which is asymmetric. This view prevailed between 1941 and 1948 when Ogston made the important suggestion that the embarrassment of the asymmetric treatment of citrate could be avoided if the acid was metabolized asymmetrically by the relevant enzymes, citrate synthase and aconitase. If the substrate was in contact with its enzyme at three or more positions a chiral center could be introduced. 

Pathways can be illustrated in a metabolic map as linear, branched or cyclic processes (Figure 1.3) and are often compartmentalized within particular subcellular location glycolysis in the cytosol and the Krebs tricarboxylic acid (TCA) cycle in... 

The metabolic machinery responsible for the heterotrophic respiration reactions is contained in specialized organelles called mitochondria. These reactions occur in three stages (1) glycolysis, (2) the Krebs or tricarboxylic acid cycle, and (3) the process of oxidative phosphorylation also known as the electron transport chain. As illustrated in... 

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