ATP to ADP ratio

ATP binds to the inhibitor site only when the protein is in the T form. In occupying the inhibitor site, ATP locks the enzyme in the inactive conformation, preventing binding of F6P (Figure 3.10). Overall, the cytosolic ratio of ATP-to-AMP ratio determines the proportion of PFK-1 in the R conformation. Compare with the effect of the ATP-to-ADP ratio on HK above (Section 3.3.1.1)... 

As is often the case, tissue-specific control mechanisms operate to optimise adaptation to particular conditions. For example, muscle contraction requires an increase in cytosolic calcium ion concentration (see Section 7.2.1, Figure 7.4). During exercise when energy generation needs to be increased, or from a more accurate metabolic point of view, when the ATP-to-ADP ratio falls rapidly, and the accompanying rise in [Ca2 + ] activate (i) glycogen phosphorylase which initates catabolism of... 

The control mechanisms operating on the TCA cycle are similar to those described for glycolysis above, that is allosteric and covalent. As might be predicted, it is the concentration of acetyl-CoA and the ATP-to-ADP and NADH-to-NAD+ ratios which are crucially important as these indicate energy status within each mitochondrion and implicitly therefore the energy status of the whole cell. High concentrations of ATP or NADH slow down the cycle, an effect which is partly mediated by covalent modification. 

What concentration of glucose would be in equilibrium with 1.0 mM glucose-6-phosphate, assuming that hexokinase is present and the concentration ratio of ATP to ADP is 5 Is it reasonable to expect an actively metabolizing cell to maintain the concentration of glucose necessary to sustain the concentration of glucose-6-phosphate at 1 mM ... 

In the standard state, the equilibrium for this reaction lies far to the left in other words, the reaction is unfavored. However, in the standard state, all the reactants and products are at one molar concentration. In other words, the ratio of ATP to ADP concentrations would be 1. In an actively metabolizing state, the ratio of ATP to ADP is as much as 50 or 100 to 1—this means that the formation of Cr P will occur to a reasonable level. Creatine phosphate forms a reservoir for high-energy phosphate in the same way that water can be pumped upstream to a reservoir and released for use later on. 

Presumably, such a mechanism calibrates the balance of ATP to ADP within the cell. During active replication, some 1,000-2,000 DnaA proteins are present in the cell, and occasionally as many as 10,000 (Donachie and Blakely 2003). These bind to either ATP or ADP, which in turn enables thermodynamic control over bacterial replication. This is because the Gibbs free energy of ATP hydrolysis depends on the ratio of ATP to ADP, not their total... 

However, activity of the competing enzyme for pyruvate, PDH, is controlled by ratios of NADH to NAD and ATP to ADP in plant mitochondria (18). During maturation of Hamlin orange the ratio of NADH to NAD in juice vesicles increased from 0.09 in October to 0.24 in March, while the phosphorylated ratio (NADPH/NADP) was constant (17). The PDH from broccoli was very sensitive to increases in the mole fraction of NADH (19). A 10 to 15% increase in ratio in whole tissue decreased PDH activity 15 to 25%. The ratio of ATP to ADP in juice vesicles increased initially from 0.7 in October but plateaued at 1.0 after December. ATP inactivated PDH by enzymic phosphorylation in mitochondr from pea leaf (20). The phosphorylated PDH was activated by a Mg -dependent phosphatase. Both reactions were inhibited by ADP which suggests... 

The ratio of ATP to ADP is kept very high, greater than 10 to 1, so the actual AG of ATP hydrolysis is probably greater than 10 kcal/mole. This means that the reaction of ATP and glucose is even more favored than it would be under the standard state. 

Mitochondria are the powerhouse of neural cells. They play a critical role in initiating both apoptotic and necrotic cell death (Fig. 4.6). By maintaining ratios of ATP ADP that thermodynamically favor the hydrolysis of ATP to ADP + Pi, they... 

The change in the ratio of ATP to ADP due to the increased ATP from glucose metabolism closes the ATP-sensitive potassium channels (K ... 

Not only is the hydrolysis of ATP to ADP and phosphate an exothermic reaction, but the concentration of ATP in cells is always very much higher than that of ADP (the ratio of ATP to ADP is about 500 1), again ensuring that the reaction will indeed proceed in the direction of ATP hydrolysis. Furthermore, the concentration of ADP... 

For all of these reactions, the equilibrium is in the direction of glycolysis, because of the utilization of ATP in the reaction and the high ratio of ATP to ADP in the cell. The reactions of phosphofructokinase and hexokinase are reversed in gluconeogenesis by simple hydrolysis of fructose bisphosphate to fructose 6-phosphate plus phosphate (catalysed by fructose bisphosphatase) and of glucose 6-phosphate to glucose plus phosphate (catalysed by glucose 6-phosphatase). 

---