Citric acid cycle control

Lowen.stein, J. M., ed., 1969. Citric Acid Cycle Control and Compartmentation. New York Marcel Dekker. 

Greville, G. D., 1969a, Intracellular compartmentation and the citric acid cycle, in Citric Acid Cycle, Control and Compartmentation (J. M. Lowenstein, ed.), pp. 1-136, Marcel Dekker, New York. 

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. 

Fe2+ Reverse citric acid cycle C02 incorporation Signalling transcription factors Control of protein synthesis (deformylation) Light capture... 

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. ... 

The overall rate of the citric acid cycle is controlled by the rate of conversion of pyruvate to acetyl-CoA and by the flux through citrate synthase, isocitrate dehydrogenase, and a-lcetoglutarate dehydrogenase. These fluxes are largely determined by the concentrations of substrates and products the end products ATP and NADH are inhibitory, and the substrates NAD+ and ADP are stimulatory. 

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. 

W. H. Holms (Control of Flux through the Citric Acid Cycle and the Glyoxylate Bypass in Escherichia coli), and R. N. Perham et al. (a-Keto Acid Dehydrogenase Complexes). 

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 ... 

ATP and ADP concentrations set the rate of electron transfer through the respiratory chain via a series of interlocking controls on respiration, glycolysis, and the citric acid cycle. 

Formation of S-aminolevulinic acid (ALA) All the carbon and nitrogen atoms of the porphyrin molecule are provided by two simple building blocks glycine (a nonessential amino acid) and succinyl CoA (an intermediate in the citric acid cycle). Glycine and succinyl CoA condense to form ALA in a reaction catalyzed by ALA synthase (Figure 21.3) This reaction requires pyridoxal phosphate as a coenzyme, and is the rate-controlling step in hepatic porphyrin biosynthesis. 

Figure 17-20 The interlocking pathways of glycolysis, gluconeogenesis, and fatty acid oxidation and synthesis with indications of some aspects of control in hepatic tissues. (— ) Reactions of glycolysis, fatty acid degradation, and oxidation by the citric acid cycle. ) Biosynthetic pathways. Some effects of insulin via indirect action on enzymes , 0, or on transcription 0/ 0. Effects of glucagon , .

What effect would the following have on the control of the citric acid cycle (a) a sudden influx of acetyl-CoA from the degradation of fatty acids, and... 

The reactions of the cycle would cease once all the NAD+ and FAD were reduced to NADH and FADH2, respectively. The reoxidation of NADH and FADH2 occurs in the electron-transport system and is slow in comparison with the potential rate at which the citric acid cycle could function. Thus, because the reoxidation of NADH and FADH2 results in energy transduction, the cycle is controlled by the energy requirements of the mitochondria. Remember that the concentrations of these oxidized and reduced cofactors in the cytoplasm and the mitochondria are quite low they must be rapidly interconverted so that metabolism can proceed. 

The third control step in the citric acid cycle is catalyzed by 2-oxoglutarate dehydrogenase. This multienzyme complex is subject to product inhibition by both NADH and succinyl-CoA. Yet again,... 

The pyruvate dehydrogenase complex is not directly a part of the reactions that constitute the citric acid cycle. It is the link between glycolysis and the citric acid cycle, and its activity is controlled by the energy status of the mitochondria. 

The product of this reaction, oxaloacetate, can either enter the gluconeogenic pathway (Chap. 11) by way of malate or condense with acetyl-CoA to yield citrate. Pyruvate carboxylase is an allosteric enzyme, and it is activated by the heterotropic effector, acetyl-CoA. Thus, pyruvate in the mitochondria is the substrate for either pyruvate dehydrogenase or pyruvate carboxylase, the activities of which, in turn, are controlled by reactants associated with the citric acid cycle. The interplay among pyruvate dehydrogenase, pyruvate carboxylase, pyruvate, and the citric acid cycle is shown in Fig. 12-9. 

K. LaNoue, W. J. Nicklas, and J. R. Williamson. Control of citric acid cycle activity in rat heart mitochondria. J. Biol. Chem., 245 102-111, 1970. 

Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled... 

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