Decarboxylation, carbohydrate conversion

Carbohydrate conversion into new industrial intermediates and end-products like propanediol, methane or syngas needs either net energy input ( reduction equivalents ) or decarboxylation, which results in a significant and costly yield loss and lowers the CO2 fixation net gain. This balance loss is also a conceptual draw-back of present fuel ethanol fermentation from sucrose and starch hydrolysates. So far, the only bulk intermediates with no or minimal... 

Thiamine pyrophosphate is a coenzyme for several enzymes involved in carbohydrate metabolism. These enzymes either catalyze the decarboxylation of oi-keto acids or the rearrangement of the carbon skeletons of certain sugars. A particularly important example is provided by the conversion of pyruvic acid, an oi-keto acid, to acetic acid. The pyruvate dehydrogenase complex catalyzes this reaction. This is the key reaction that links the degradation of sugars to the citric acid cycle and fatty acid synthesis (chapters 16 and 18) ... 

Acetyl-CoA is the only compound that can enter the TCA cycle when the cycle is operating purely oxidatively, but one molecule of oxaloacetate must enter for each molecule of citrate, a-ketoglutarate, or succinyl-CoA that is removed for use in biosynthesis. It follows that pyruvate is a major metabolic branchpoint in a cell that is living on carbohydrate. The partitioning of pyruvate between decarboxylation to acetyl-CoA and carboxylation to oxaloacetate is, in effect, partitioning between the two major metabolic uses of pyruvate oxidation of carbon for regeneration of ATP and conversion to starting materials for biosynthesis. 

Although citrate has been excluded as the primary condensation product of pyruvate and oxalacetate, no direct evidence bearing upon the nature of this product has as yet been obtained. The participation of cfs-aconitic and isocitric acids is speculative. Nor is there any evidence supporting the hypothesis that pyruvate and oxalacetate condense to form a hypothetical intermediate oxalcitraconic acid which can be oxidatively decarboxylated to citric acid. Since citrate, aconitate and isocitrate are in equilibrium with each other, the participation of the last two substances as intermediates of carbohydrate oxidation would, on the surface, appear to be doubtful. Krebs, however, believes that the conversion of cis-aconitate to a-ketoglutarate occurs so rapidly in liver that equilibrium with citrate is not attained. 

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. 

In animals TPP-dependent decarboxylation reactions are essential to the production of energy needed for cell metahohsm. In these reactions a-ketoacids are converted to acyl CoA molecules and carbon dioxide. The reactions (e.g., the conversion of pyruvate to acetyl CoA) are an important part of the breakdown of carbohydrates, and of the conversion of several classes of molecules (carbohydrates, fats, and proteins) to energy, carbon dioxide, and water in the citric acid cycle. In other organisms, in addition to its participation in the above reactions, TPP is a required coenzyme in alcohol fermentation, in the carbon fixation reactions of photosynthesis, and in the hiosynthesis of the amino acids leucine and valine. 

Decarboxylases are known for their roles in a wide variety of catabolic and anabolic pathways, including decarboxylation of a- and p-keto acids, amino acid conversions, and carbohydrate biosynthesis. Mechanistically, a decarboxylation has parallels to retro-aldol cleavage reactions (Figure 1.32). 

Oxidative decarboxylation (removal of CO,) in carbohydrate metabolism is also involved in the Krebs cycle in the conversion of alpha-ketoglutaric acid to succinic acid. Because fats and amino acids, as well as carbohydrates, can contribute to alpha-ketoglutaric acid, it follows that thiamin is involved in the metabolism of all three energy producing units. 

Decarboxylation reactions are common in Nature and they are involved in many pathways, including decarboxylation of keto acids, amino acid conversions, and carbohydrate synthesis. Many decarboxylases use cofactors such as metal ions, pyridoxal 5 -phosphate, biotin, and flavin, but a small subset, for example, orotidine 5 -phosphate decarboxylase (ODCase) and methyhnalonyl CoA decarboxylase do not utilize any cofactor. ODCase catalyzes the decarboxylation of orotic acid (shown in Figure 8), and it generates one of the largest rate enhancements known to be produced by any enzyme (rate of the reaction is enhanced by a factor of Several... 

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