Treatment tricarboxylic acid cycle

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. 

The increased degradation of fat that occurs in insulin deficiency also has serious effects. Some of the fatty acids that accumulate in large quantities are taken up by the liver and used for lipoprotein synthesis (hyperlipidemia), and the rest are broken down into acetyl CoA. As the tricarboxylic acid cycle is not capable of taking up such large quantities of acetyl CoA, the excess is used to form ketone bodies (acetoacetate and p-hydroxy-butyrate see p. 312). As H"" ions are released in this process, diabetics not receiving adequate treatment can suffer severe metabolic acidosis (diabetic coma). The acetone that is also formed gives these patients breath a characteristic odor. In addition, large amounts of ketone body anions appear in the urine (ketonuria). 

Hassel B, Sonnewald U (1995) Selective inhibition of the tricarboxylic acid cycle of GABAergic neurons with 3-nitropropionic add in vivo. J Neurochem 65 1184-1191 Henry PG, Lebon V, Vaufrey F, BrouiUet E, Hantraye P, Bloch G (2002) Decreased TCA cycle rate in the rat brain after acute 3-NPA treatment measured by in vivo 1H-[13C] NMR spectroscopy. J Neurochem 82 857-866... 

The reduction in urinary elimination in untreated diabetic patients affects not only citric acid. Indeed, Osteux and Laturaze (07) have shown that the same holds true for the other acids of the tricarboxylic acid cycle treatment with insulin re-establishes a normal elimination of these acids. Treatment with antidiabetic sulfonamides also increases the urinary citrate in such patients (OlO). 

Though less than 1% of the total iron in the body is utilized for enzymes and cofactors, the critical nature of these enzymes in such major metabolic pathways as the tricarboxylic acid cycle could easily explain brain effects of iron deficiency. Pollitt and Leibel (1976) also suggest that central catecholamine excess causes some of the behavioral disturbances attributed to iron deficiency. Monoamine oxidase is functionally deranged in iron-deficient rats. Children with iron-deficient anemia have elevated urinary norepinephrine excretion which is normalized within 1 wk after parenteral iron treatment. Potentially toxic excess heme precursors, protoporphyrins, may also mediate the behavioral effects of iron deficiency. 

Citric acid, found in citrus fruits, is listed as an inhibitor, and also occurs as a reaction intermediate in the metabolic tricarboxylic acid or dtric acid cycle. Ethanol or ethyl alcohol makes an unexpected appearance as an inhibitor, as does glycerol. The ubiquitous alkaloid ingredient of coffee, better known as caffeine, is listed as an inhibitor (in fact, coffee enemas are sometimes used in folkloric cancer treatments). Creatine, a nitrogenous compound found naturally in the body, is an inhibitor, and is a known anticancer agent, for example, as used with urea in a nuxture called Carbatine. 

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