title: Model and simulation of Na+/K+ pump phosphorylation in the presence of palytoxin.
abstract: The ATP hydrolysis reactions responsible for the Na(+)/K(+)-ATPase phosphorylation, according to recent experimental evidences, also occur for the PTX-Na(+)/K(+) pump complex. Moreover, it has been demonstrated that PTX interferes with the enzymes phosphorylation status. However, the reactions involved in the PTX-Na(+)/K(+) pump complex phosphorylation are not very well established yet. This work aims at proposing a reaction model for PTX-Na(+)/K(+) pump complex, with similar structure to the Albers-Post model, to contribute to elucidate the PTX effect over Na(+)/K(+)-ATPase phosphorylation and dephosphorylation. Computational simulations with the proposed model support several hypotheses and also suggest: (i) phosphorylation promotes an increase of the open probability of induced channels; (ii) PTX reduces the Na(+)/K(+) pump phosphorylation rate; (iii) PTX may cause conformational changes to substates where the Na(+)/K(+)-ATPase may not be phosphorylated; (iv) PTX can bind to substates of the two principal states E1 and E2, with highest affinity to phosphorylated enzymes and with ATP bound to its low-affinity sites. The proposed model also allows previewing the behavior of the PTX-pump complex substates for different levels of intracellular ATP concentrations.
authors: Biomedical Engineering Program, COPPE, Federal University of Rio de Janeiro, Brazil.
authors: Antônio M
authors: AM
authors: Rodrigues
authors: Antônio-Carlos G
authors: AC
authors: Almeida
authors: Antonio F C
authors: AF
authors: Infantosi
authors: Hewerson Z
authors: HZ
authors: Teixeira
authors: Mario A
authors: MA
authors: Duarte
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D003064:Cnidarian Venoms; D003198:Computer Simulation; D008954:Models, Biological; D010766:Phosphorylation; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry*; D000095702:Polyether Toxins
chemical_list: D000178:Acrylamides; D003064:Cnidarian Venoms; D000254:Sodium-Potassium-Exchanging ATPase; C010272:palytoxin; D000095702:Polyether Toxins