ADP/ATP ratio

As discussed earlier, a decrease in muscle MgATP could inhibit Ca release from the SR, by lowering ATP content and increasing the free Mg. A fall in the ATP/ADP ratio may also inhibit Ca release by slowing Cd reuptake into the SR. A better preserved ATP/ADP ratio in exercising muscle as a result of increased creatine content could counteract the inhibition of Ca " kinetics and delay fatigue. 

Brain hexokinase is inhibited by its product glucose-6-phosphate and to a lesser extent by adenosine diphosphate. The isoenzyme of hexokinase found in brain may be soluble in the cytosol or be attached firmly to mitochondria [2 and references therein]. An equilibrium exists between the soluble and the bound enzyme. The binding changes the kinetic properties of hexokinase and its inhibition by Glc-6-P resulting in a more active enzyme. The extent of binding is inversely related to the ATP ADP ratio, i.e. conditions in which energy utilization... 

Figure 9.23 Properties of the three enzymes that control the flux through the Krebs cycle. During physical activity. The CoASH/ succinyl CoA concentration ratio increases whereas that of ATP/ADP ratio decrease. These changes increase the flux through the cycle.

In (a) the sprint, and middle-distance running there is little change in the glycogen content but a marked decrease in that of phosphocreatine and a marked increase in that of phosphate and a decrease in pH. The precise and relevant concentration of ADP in muscle is not easy to measure, since most of it is bound. Hence the data are not presented but the concentration can be calculated from the change in phosphocreatine concentration. This indicates that the decrease in the ATP/ADP ratio is tenfold. 

Inhibition of Ca + binding to troponin by H. Inhibition by high P concentration or low ATP/ADP ratio. 

Although this reaction is fully reversible, the relatively high [ATP]/[ADP] ratio in cells normally drives the reaction to the right, with the net formation of NTPs and dNTPs. The enzyme actually catalyzes a two-step phosphoryl transfer, which is a classic case of a double-displacement (Ping-Pong) mechanism (Fig. 13-12 see also Fig. 6-13b). First, phosphoryl group transfer from ATP to an active-site His residue produces a phosphoenzyme... 

After the protection of its DNA from damage, perhaps nothing is more important to a cell than maintaining a constant supply and concentration of ATP. Many ATP-using enzymes have Km values between 0.1 and 1 mM, and the ATP concentration in a typical cell is about 5 mM. If [ATP] were to drop significantly, the rates of hundreds of reactions that involve ATP would decrease, and the cell would probably not survive. Furthermore, because ATP is converted to ADP or AMP when spent to accomplish cellular work, the [ATP]/[ADP] ratio profoundly affects all reactions that employ these cofactors. The same is true for other important cofactors, such as NADH/NAD"1" and NADPH/NADP+. For example, consider the reaction catalyzed by hexokinase ... 

Because an alteration of this mass action ratio profoundly influences every reaction that involves ATP, organisms have been under strong evolutionary pressure to develop regulatory mechanisms that respond to the [ATP]/[ADP] ratio. Similar arguments show the importance of maintaining appropriate [NADH]/[NAD+] and [NADPH]/[NADP+] ratios. 

Which one of the following conditions decreases the oxidation of acetyl CoA by the citric acid cycle A. A low ATP/ADP ratio B. A low NADH due to rapid oxidization to NAD+ through the respiratory chain C. A low NAD+/NADH ratio D. A high concentration of AMP E. A low GTP/GDP ratio Correct answer = C. A low NAD /NADH ratio limits the rates of the NAD+-requiring dehydro genases. A low ATP/ADP or GTP/GDP ratio stimulates the cycle. AMP does not directly affect the eye e. 

The [ATP] / [ADP] ratio in an actively respiring yeast cell is about 10. What would be the intracellular [3-phosphoglycerate] / [1,3-bisphospho-glycerate] ratio have to be to make the phospho-glycerate kinase reaction (Fig. 9-7, reaction 7) proceed toward 1,3-bisphosphoglycerate synthesis at 25°C, pH 7 ... 

After these general comments let us further test the idea of thermodynamic buffering on an experimental basis by repeating the above experiment but this time in the presence of an inhibitor of adenylate kinase, namely, diadenosine pentaphosphate. As is depicted in Fig. 6b the buffering effect of the adenylate kinase is abolished by inhibiting this enzyme and it becomes now possible to drive the system beyond the state of optimal efficiency by increasing the hexokinase concentration in the medium. Note that it was not possible to measure points closer to level flow than the ones shown in the figure. This is due to technical reasons. At the lowest phosphate potentials the ATP/ADP ratios where of the order... 

Deficient respiratory chain function caused by mtDNA mutations could affect various biochemical functions of mitochondria, such as mitochondrial membrane potential, ATP synthesis, ATP/ADP ratio, ROS production, and calcium homeostasis (S14). 

Answer Within organelles, reaction intermediates and enzymes can be maintained at different levels from those in the cytosol and in other organelles. For example, the ATP/ADP ratio is lower in mitochondria than in the cytosol because the role of adenine nucleotides in the mitochondrial matrix is to accept a phosphoryl group, whereas the role in the cytosol is to donate a phosphoryl group. Similarly, different NADH/NAD+ and NADPH/NADP+ ratios reflect the reductive (biosynthetic) functions of the cytosol and the oxidative (catabolic) functions of the mitochondrial matrix. By segregating reaction sequences that share intermediates, the cell can regulate catabolic and anabolic processes separately. 

Function of mitochondria is also commonly monitored as an indicator of cellular toxicity. Mitochondrial uptake and retention of the fluorescent dye, rhodamine 123, can be visualized microscopically. Biochemical measurements of mitochondrial function include the ATP-ADP ratio and dehydrogenase activity with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), which yields a colored formazan product upon reduction. The dye, neutral red (3-amino-7-dimethyl-amino-2-methylphenazine hydrochloride), targets lysosomes, and its retention is inversely related to cytotoxicity. Commercially available versions of the MTT and neutral red assays have been adapted to microtiter plate formats to provide highly efficient screening assays. Examples of how cell-type-specific functions can be followed as indicators of cell toxicity are included in Table 8.1. 

Elevation in the ATP/ADP ratio induces closure of cell-surface ATP-sensitive K+ channels, leading to cell-membrane depolarisation. 

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