Carbohydrate metabolism aerobic

This chapter is mainly concerned with the contribution of the tricarboxylic acid cycle to carbohydrate metabolism. The TCA cycle is the main source of electrons for oxidative phosphorylation, and thereby the major energetic sequence in the metabolism of aerobic cells or organisms. It serves as the main distribution center of metabo-... 

Van Oordt, B.E., Tielens, A.G. and van den Bergh, S.G. (1989) Aerobic to anaerobic transition in the carbohydrate metabolism of Schistosoma mansoni cercariae during transformation in vitro. Parasitology 98, 409-415. 

The major end-products of carbohydrate metabolism in this species are lactate and succinate. The relative amount formed of each depends on the presence or absence of oxygen in the incubation medium, the presence or absence of glucose, and the presence or absence of fumarate. For example, anaerobiosis leads to an increase in lactate production, which is accompanied by a fall in the intracellular level of malate. Malate is an inhibitor of pyruvate kinase in M. expansa, so the fall in malate levels results in an increase in pyruvate kinase activity leading to a rise in lactate production. Conversely, under aerobic conditions, malate levels increase, pyruvate kinase activity is inhibited and lactate production is decreased (Fig. 5.5). 

Cyanide is described as a cellular toxin because it inhibits aerobic metabolism. It reversibly binds with ferric (Fe " ") iron-containing cytochrome oxidase and inhibits the last step of mitochondrial oxidative phosphorylation. This inhibition halts carbohydrate metabolism from citric acid cycle, and intracellular concentrations of adenosine triphosphate are rapidly depleted. When absorbed in high enough doses, respiratory arrest quickly ensues, which is probably caused by respiratory muscle failure. Cardiac arrest and death inevitably follow. 

The phase of primary respiratory alkalosis rarely is recognized in children with salicylate toxicity. They usually present in a state of mixed respiratory and renal acidosis, characterized by a decrease in blood pH, a low plasma bicarbonate concentration, and normal or nearly normal plasma PCO2. Direct salicylate-induced depression of respiration prevents adequate respiratory hyperventilation to match the increased peripheral production of CO2- Consequently, plasma PCO2 increases and blood pH decreases. Because the concentration of bicarbonate in plasma already is low due to increased renal bicarbonate excretion, the acid-base status at this stage essentially is an uncompensated respiratory acidosis. Superimposed, however, is a true metabolic acidosis caused by accumulation of acids as a result of three processes. First, toxic concentrations of salicylates displace 2-3 mEq/L of plasma bicarbonate. Second, vasomotor depression caused by toxic doses of salicylates impairs renal function, with consequent accumulation of sulfuric and phosphoric acids. Third, salicylates in toxic doses may decrease aerobic metabolism as a result of inhibition of various enzymes. This derangement of carbohydrate metabolism leads to the accumulation of organic acids, especially pyruvic, lactic, and acetoacetic acids. 

In carbohydrate metabolism, the energy released by oxidation reactions is used to drive the production of ATP, with most of the ATP produced in aerobic processes. In the same aerobic processes—namely, the citric acid cycle and oxidative phosphorylation—the energy released by the oxidation of acetyl-GoA formed by P-oxidation of fatty acids can also be used to produce ATP. There are two sources of ATP to keep in mind when calculating the overall yield of ATP. The first source is the reoxidation of the NADH and FADHg produced by the P-oxidation of the fatty acid to acetyl-GoA. The second source is ATP production from the processing of the acetyl-GoA through the citric acid cycle and oxidative phosphorylation. We shall use the oxidation of stearic acid, which contains 18 carbon atoms, as our example. 

The early work of Meyerhof showed that there was an intimate connection between resynthesis of carbohydrate and aerobic metabolism. When the production of lactic acid by tissues under anaerobic conditions was compared with the production of lactic acid under aerobic conditions, it was found that the uptake of 1 mole of respired oxygen inhibited the formation of 1 to 2 moles of lactic acid i.e., three to six times as much lactic acid as could have been oxidized by the observed oxygen uptake. This phenomenon of the suppression of glycolysis under aerobiosis has been called by Warburg the Pasteur effect. 

TOXICATsTTS AFFECTING AEROBIC METABOLISM. The high energy demands of the heart make it susceptible to toxicants that interfere with oxy n availability, carbohydrate metabolism, or oxidative phosphorylation. 

Phosphate is again present in an energy-rich form (namely the enol ester). It can be transferred by phosphopyruvate kinase to ADP this transfer affords pyruvic acid, which is the most important metabolite of both anaerobic and aerobic carbohydrate metabolism. 

Helminths are characterized by a high rate of carbohydrate metabolism associated with incomplete substrate oxidation. This is the case whether they live anaerobically (as intestinal worms do) or aerobically (like schistosomes). The Meyerhof sequence is the major metabolic pathway in worms for the utilization of carbohydrate. Trehalose (see above) plays an important part in helminth carbohydrate metabolism. For a review of helminth biochemistry, see von Brand (1974). 

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