Citric acid cycle regulation

The Amphibolic Citric Acid Cycle Citric Acid Cycle Regulation... 

Regulation of the Citric Acid Cycle Depends Primarily on a Supply of Oxidized Cofactors... 

In most tissues, where the primary role of the citric acid cycle is in energy-yielding metabohsm, respiratory control via the respiratory chain and oxidative phosphorylation regulates citric acid cycle activity (Chapter 14). Thus, activity is immediately dependent on the supply of NAD, which in turn, because of the tight couphng between oxidation and phosphorylation, is dependent on the availabihty of ADP and hence, ulti-... 

Ketogenesis is regulated at three cmcial steps (1) control of free fatty acid mobihzation from adipose tissue (2) the activity of carnitine palmitoyltransferase-1 in hver, which determines the proportion of the fatty acid flux that is oxidized rather than esteri-fied and (3) partition of acetyl-CoA between the pathway of ketogenesis and the citric acid cycle. 

The rates of oxidative phosphorylation and the citric acid cycle are closely coordinated, and are dependent mainly on the availability of and ADR If is limited, the rate of oxidative phosphorylation decreases, and the concentrations of NADH and FADH increase. The accumulation of NADH, in turn, inhibits the citric acid cycle. The coordinated regulation of these pathways is known as respiratory control. ... 

Although the individual reactions of the citric acid cycle were initially worked out in vitro, using minced muscle tissue, the pathway and its regulation have also been studied extensively in vivo. By using radioactively la-... 

The other anaplerotic reactions shown in Table 16-2 are also regulated to keep the level of intermediates high enough to support the activity of the citric acid cycle. Phosphoenolpyruvate (PEP) carboxylase, for example, is activated by the glycolytic intermediate fructose 1,6-bisphosphate, which accumulates when the citric acid cycle operates too slowly to process the pyruvate generated by glycolysis. 

The Citric Acid Cycle Is Regulated at Its Three Exergonic Steps... 

The flow of metabolites through the citric acid cycle is under stringent regulation. Three factors govern the rate of flux through the cycle substrate availability, inhibition by accumulating products, and allosteric feedback inhibition of the enzymes that catalyze early steps in the cycle. 

The partitioning of isocitrate between the citric acid cycle and the glyoxylate cycle is controlled at the level of isocitrate dehydrogenase, which is regulated by reversible phosphoiylation. 

A detailed review of the regulation of the citric acid cycle. 

On the basis of these observations, suggest how succinyl-CoA regulates the activity of citrate synthase. (Hint See Fig. 6-29.) Why is succinyl-CoA an appropriate signal for regulation of the citric acid cycle How does the regulation of citrate synthase control the rate of cellular respiration in pig heart tissue ... 

Williamson, J. R., and Cooper, R. V., Regulation of the citric acid cycle in mammalian systems. FEBS Lett. 

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