Ans. D. 3:2. (Ref Ganong 23rd/ Ch. 32).NA, K ATPASENa, K ATPase catalyzes the hydrolysis of ATP to ADP and uses the energy to extrude three Na+ from the cell and take two K+ into the cell for each molecule of ATP hydrolyzed. It is an electrogenic pump in that it moves three positive charges out of the cell for each two that it moves in, and it is therefore said to have a coupling ratio of 3:2. It is found in all parts of the body. Its activity is inhibited by ouabain and related digitalis glycosides used in the treatment of heart failure. It is a heterodimer made up of an alpha subunit with a molecular weight of approximately 100,000 and a beta subunit with a molecular weight of approximately 55,000. Both extend through the cell membrane. Separation of the subunits eliminates activity. The beta subunit is a glycoprotein, whereas Na+ and K+ transport occur through the alpha subunit. The beta subunit has a single membrane-spanning domain and three extracellular glycosylation sites, all of which appear to have attached carbohydrate residues. These residues account for one third of its molecular weight. The alpha subunit probably spans the cell membrane 10 times, with the amino and carboxyl terminals both located intracellularly. This subunit has intracellular Na+- and ATP-binding sites and a phosphorylation site; it also has extracellular binding sites for K+ and ouabain. The endogenous ligand of the ouabain-binding site is unsettled. When Na+ binds to the alpha subunit, ATP also binds and is converted to ADP, with a phosphate being transferred to Asp 376, the phosphorylation site. This causes a change in the configuration of the protein, extruding Na+ into the ECF. K+ then binds extracellularly, dephosphorylating the alpha subunit, which returns to its previous conformation, releasing K+ into the cytoplasm.Na+-K+ ATPase is located in the plasma membrane with ATP site on cytoplasmic side. For each ATP consumed, 3 Na+ go out and 2 K+ come in. During cycle, pump is phosphorylated.Ouabain inhibits by binding to K+ site.Cardiac glycosides (digoxin and digitoxin from foxglove) also inhibit the Na+-K+ ATPase, causing T cardiac contractility. Also know:The cells of the proximal and distal tubules, like the cells of the gastric glands, secrete hydrogen ions. Acidification also occurs in the collecting ducts. The reaction that is primarily responsible for H+ secretion in the proximal tubules is Na-H exchange. This is an example of secondary active transport; extrusion of Na+ from the cells into the interstitium by Na, K ATPase lowers intracellular Na+, and this causes Na+ to enter the cell from the tubular lumen, with coupled extrusion of H+ The H+ comes from intracellular dissociation of H2CO3, and the HCO3 that is formed diffuses into the interstitial fluid. Thus, for each H+ ion secreted, one Na+ ion and one HCO3 ion enter the interstitial fluid.Type of transportEnergy sourceExampleOther characteristicsClinical correlationSimple diffusionPassivePulmonary gases--Pulmonary edema decreases diffusionCarrier-mediated or facilitated diffusionPassiveGlucose uptake by muscleInsulin controls carrier population CHemical specificityInsulin-dependent glucose uptake impaired in diabetes mellitusPrimary active transportDirect use of ATPNa+/K+-ATPaseH+/K+-ATPaseAntiport (countertransport)Inhibition by cardiac glycosidesSecondary active transportElectrochemical gradient for sodium is most common driving forceNa+-glucose in kidneyNa+-H+ exchangeSymport (cotransport) Antiport (countertransport)Osmotic diuresis results when transporters saturated Renal tubular acidosis