Adenosine triphosphate depletion

The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase. Biochem. J. 162 601-609 (1977). 

D2. Dallegri, F., Goretti, R., Ballestrero, A., Ottonello, L., and Patrone, F., Neutrophil-induced depletion of adenosine triphosphate in target cells Evidence for a hypochlorous acid-mediated process. J. Lab. Clin. Med. 112, 765-772 (1988). 

Taylor B. F. and Oremland R. S. (1979) Depletion of adenosine triphosphate in Desulfovibrio by oxyanions of Group VI elements. Curr. Microbiol. 3, 101 — 103. 

Chlorophenols block adenosine triphosphate (ATP) production, without blocking the electron transport chain. They inhibit oxidative phosphorylation, which increases basal metabolic rate and increases body temperature. As body temperature rises, heat-dissipating mechanisms are overcome and metabolism is accelerated. Adenosine diphosphate (ADP) and other substrates accumulate, and stimulate the electron transport chain further. This process demands more oxygen in a futile effort to produce ATP. Oxygen demand quickly surpasses oxygen supply and energy reserves of the body become depleted. 

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. 

Phosphorus is essential in respiratory disease for its role in the synthesis of adenosine triphosphate, inadequate stores of which can lead to respiratory muscle weakness. Critically ill, malnourished patients are at risk for phosphorus depletion. 

Adenosine triphosphate (ATP) is the primary energy source for ceU-free synthesis reactions. Rapid depletion of ATP leads to the cessation of translation in under an hour in batch mode. ATP regeneration systems are used to extend the life of translation reactions by maintaining a stable ATP concentration. ATP is regenerated by the enzyme-catalyzed transfer of high-energy phosphate bonds from a secondary energy... 

Vinca alkaloids are lipophilic molecules that can readily cross membranes by simple diffusion [186]. Experiments performed with several human cancer and tissue cell lines have shown in all cases rapid uptake of every one of Vinca alkaloids [23, 187-189]. Uptake is thought to occur by diffusion although energy dependence or independence of the uptake is seldom mentioned in reports. However, for instance in cultured human promyelocytic leukemia HL-60/C1 cells it has been shown that rates of uptake of vinblastine were unaffected by depletion of cellular adenosine triphosphate, reinforcing that uptake is not mediated by an energy-dependent system [189]. 

An ADA-resistant purine analog, cladribine (2-chlorodeoxyadenosine 2-CdA) has demonstrated potent activity in hairy cell leukemia, CLL, and low-grade lymphomas. After intracellular phosphorylation by deoxycytidine kinase and conversion to cladribine triphosphate, it is incorporated into DNA. It produces DNA strand breaks and depletion of NAD and adenosine triphosphate (ATP), as well as apoptosis, and is a potent inhibitor of ribonucleotide reductase. The drug does not require cell division to be cytotoxic. Resistance is associated with loss of the activating enzyme, deoxycytidine kinase, or escape of ribonucleotide reductase from inhibition. 

Mechanism of Action. The drug specifically blocks the glucose uptake by susceptible heliminths, thereby depleting the stored glycogen within the parasite. Obviously, the glycogen depletion invariably causes in an actual decreased generation of adenosine triphosphate (ATP), the latter is essentially needed for the survival and reproduction of the helminth. Besides, it inhibits cell-division in nematodes. ... 

In strains dependent on Pit for inorganic phosphate uptake, exposure to arsenate leads to the depletion of intracellular adenosine triphosphate (ATP) stores and the intracellular accumulation of arsenate, demonstrating the direct interference of arsenate in phosphate metabolism (4). 

Galloway, R.J. and Taylor, B.L. (1980). Histidine starvation and adenosine 5-triphosphate depletion in chemotaxis of Salmonella typhimurium. J. Bacterial. 144, 1068-1075. 

In a subsequent study, rabbit corneal epithelial and human conjunctival epithelial cells were incubated with 0, 5, 25, 50, 100, 250, 500 or 750 mg sodium chlorite/l. Depletion of cellular adenosine triphosphate (ATP) occurred at concentrations above 100 mg/l for rabbit corneal epithelial cells and above 50 mg/ I for human conjunctival epithelial cells. GSH was depleted progressively between 5 and 250 mg/l in both cell types. The authors concluded that sodium chlorite is of low toxicity to ocular cells (Ingram et al., 2004). 

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