Succinate glucose oxidation

When complex I is defective, there is an excess of cellular NADH, which pushes the lactate dehydrogenase to form lactate from pyruvate (anaerobic glycolysis). This results in higher than normal utilization of glucose, causing hypoglycemia. Because succinate is oxidized at the complex II level, its oxidation is not affected. 

Succinyl-CoA derived from propionyl-CoA can enter the TCA cycle. Oxidation of succinate to oxaloacetate provides a substrate for glucose synthesis. Thus, although the acetate units produced in /3-oxidation cannot be utilized in glu-coneogenesis by animals, the occasional propionate produced from oxidation of odd-carbon fatty acids can be used for sugar synthesis. Alternatively, succinate introduced to the TCA cycle from odd-carbon fatty acid oxidation may be oxidized to COg. However, all of the 4-carbon intermediates in the TCA cycle are regenerated in the cycle and thus should be viewed as catalytic species. Net consumption of succinyl-CoA thus does not occur directly in the TCA cycle. Rather, the succinyl-CoA generated from /3-oxidation of odd-carbon fatty acids must be converted to pyruvate and then to acetyl-CoA (which is completely oxidized in the TCA cycle). To follow this latter route, succinyl-CoA entering the TCA cycle must be first converted to malate in the usual way, and then transported from the mitochondrial matrix to the cytosol, where it is oxida-... 

Succinic add source of carbon and energy improves metabolic balance between carbon flux from glucose and oxidation throgh TCA cyde. 

These short-chain fatty acids are acetic, butyric, lactic and propionic acids, also known as volatile fatty acids, VFA. They are produced from fermentation of carbohydrate by microorganisms in the colon and oxidised by colonocytes or hepatocytes (see above and Chapter 4). Butyric acid is activated to produce butyryl-CoA, which is then degraded to acetyl-CoA by P-oxidation acetic acid is converted to acetyl-CoA for complete oxidation. Propionic acid is activated to form propionyl-CoA, which is then converted to succinate (Chapter 8). The fate of the latter is either oxidation or, conversion to glucose, via glu-coneogenesis in the liver. 

Complete oxidation of a molecule of glucose to C02 and H20 generates approximately 30 molecules of ATP. Reoxidation of eight molecules of NADH in the mitochondrial matrix yields about 20 molecules of ATP (2.5 ATP per molecule of NADH). Reoxidation of two molecules of FADH2 bound to succinate dehydrogenase yields 3 molecules of ATP (1.5 per molecule of FADH2). Two molecules of ATP are produced in glycolysis, and the TCA cycle produces two more ATP via GTP. The latter two molecules of ATP are equivalent... 

Rat liver mitochondria were isolated as described (4). The initial rate of ATP synthesis associated with the oxidation of succinate was followed by monitoring fluorometrically the ATP-linked NADPH production in the presence of hexokinase and glucose-6-phosphate dehydrogenase (10). Control experiments showed no interference from unexpected reduction of NADP+ or from electron backflow. Possible ATP formation via mitochondrial adenylate... 

The structure of the uronic acid was established as follows (a) periodate oxidation, followed by bromine oxidation, gave 2-hydroxy-3-methoxy-L-erj/f/tro-succinic acid 1413 (b) reduction of the methyl glycoside methyl ester with lithium aluminum hydride, followed by hydrolysis, gave 4-0-methyl-D-glucose.13... 

Each of the three NADH molecules produced per turn of the cycle yields 3 ATPs and the single FADH2 yields 2 ATPs by oxidative phosphorylation (although some measurements indicate that the quantities are 2.5 and 1.5 respectively - see p. 355). One GTP (or ATP) is synthesized directly during the conversion of succinyl CoA to succinate. Thus the oxidation of a single molecule of glucose via the citric acid cycle produces 12 ATP molecules. 

In this section, we seek to identify materials that are the reasonable first structures to arise from biomass deconstruction, and to describe how chemically catalyzed processes are being developed for their production. For that reason, commercially practiced processes that use catalysis, such as the reduction of glucose to sorbitol, are mentioned only briefly or not at all. Chemical catalysis will certainly play an additional role in the further conversion of these initial building blocks into secondary intermediates or final marketplace products (e.g., oxidative conversion of levulinic acid into succinic acid), but such multistep possibilities are outside the scope of this discussion. 

Iodine as an Oxidant. Brunner and Chuard concluded that iodine had no action on D-glucose. The sugar was treated with iodine and dilute ethanol in the presence of succinic acid at 110° for several hours from the brown reaction mixture a monoiodosuccinic acid was obtained, but the D-glucose was apparently unaltered. 

For succinate-grown yeast, extracts catalyze D-glucitol — xyZo-hexulose + glucose, D-mannitol — fructose + mannose, ribitol — ribose, xylitol — xylose + threo-pentu-lose, D-arabinitol — arabinose + fhreo-pentulose, and oxidation of NADPH with D-fructose, L-xyZo-hexulose, D-ribose, D-xylose, or L-arabinose.284... 

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