Primary active transporters

It is clearly impossible to give a comprehensive overview of this rapidly expanding field. I have chosen a few experts in their field to discuss one (class of) transport protein(s) in detail. In the first five chapters pumps involved in primary active transport are discussed. These proteins use direct chemical energy, mostly ATP, to drive transport. The next three chapters describe carriers which either transport metabolites passively or by secondary active transport. In the last three chapters channels are described which allow selective passive transport of particular ions. The progress in the latter field would be unthinkable without the development of the patch clamp technique. The combination of this technique with molecular biological approaches has yielded very detailed information of the structure-function relationship of these channels. 

Active transport. The definition of active transport has been a subject of discussion for a number of years. Here, active transport is defined as a membrane transport process with a source of energy other than the electrochemical potential gradient of the transported substance. This source of energy can be either a metabolic reaction (primary active transport) or an electrochemical potential gradient of a substance different from that which is actively transported (secondary active transport). 

The liver plays an important role in determining the oral bioavailability of drags. Drag molecules absorbed into the portal vein are taken up by hepatocytes, and then metabolized and/or excreted into the bile. For hydrophilic drugs, transporters located on the sinusoidal membrane are responsible for the hepatic uptake [1, 2]. Biliary excretion of many drags is also mediated by the primary active transporters, referred to as ATP-binding cassette transmembrane (ABC) transporters, located on the bile canalicular membrane [1, 3-5], Recently, many molecular biological... 

Niinuma, K., Kato, Y., Suzuki, H., Tyson, C. A., Weizer, V., Dabbs, J. E., Froehlich, R., Green, C. E., Sugiyama, Y., Primary active transport of organic anions on bile canalicular membrane in humans, Am. J. Physiol. 1999, 276, G1153-G1164. 

Other Primary Active Transporters (not Diphosphate-Bond-Hydrolysis Driven)... 

Ishikawa, T., Muller, M., Klunemann, C., Schaub, T. and Keppler, D. (1990) ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates. Journal of Biological Chemistry, 265, 19279-19286. 

Besides by interfering with the general energy maintenance of the cell, impact of active transport during intracellular accumulation can also be investigated by direct inhibition of certain transport mechanisms. To detect contribution of Na+-dependent transport, the Na+/K+-ATPase, one of the primary active transport systems of the cell, can be inhibited by ouabain at 10 /uM. Higher amounts of the inhibitor may seriously impede with the viability of the cell. To obtain reliable results, the cells are pretreated with ouabain for 15 min prior to addition of the analyte. Usually, the inhibitory effect of ouabain lasts up to 45 min [29],... 

The transport is directly coupled to adenosine triphosphate (ATP) hydrolysis, which is known as primary active transport. 

Though drugs appear to cross the blood-brain barrier by passive diffusion, transporter systems in the blood-brain barrier pump drugs back out into the systemic circulation. As in the gut, the Pgp transporter system is the primary active transporter in the blood-brain barrier identified to date. This ATP-dependent transporter system picks up substrates that have crossed the capillary endothelial cells and transports them back to the systemic circulation, limiting their penetration into the CNS. Thus, not only are the physicochemical properties of the drug a determinant for penetration into the CNS but penetration also depends on whether the drug is a substrate for the Pgp transporter system. 

Primary active transport (against electrochemical gradient)... 

In virtually every animal cell type, the concentration of Na+ is lower in the cell than in the surrounding medium, and the concentration of K+ is higher (Fig. 11-36). This imbalance is maintained by a primary active transport system in the plasma membrane. The enzyme Na+K+ ATPase, discovered by Jens Slcou in 1957, couples breakdown of ATP to the simultaneous movement of both Na+ and K+ against their electrochemical gradients. For each molecule of ATP converted to ADP and I , the transporter moves two K+ ions inward and three Na+ ions outward across the plasma membrane. The Na+K+ ATPase is an integral protein with two subunits (Mr -50,000 and -110,000), both of which span the membrane. 

Carriers, like enzymes, show saturation and stereospecificity for their substrates. Transport via these systems may be passive or active. Primary active transport is driven by ATP or electron-transfer reactions secondary active transport, by coupled flow of two solutes, one of which (often H+ or Na+) flows down its electrochemical gradient as the other is pulled up its gradient. 

Human - ABC transporters (primary active transport) - 146X02... 

Niinuma K, Kato Y, Suzuki H, et al. Sugiyama. Primary active transport of organic anions on bile canalicular membrane in humans. Am J Physiol 1999 276 G1153-G1164. 

Primary Active Transport SaturaHon/Carnpelttton ATP Hydrolysis... 

Primary active transport Primary active transport is quite... 

Energy is provided, for example, by ATP for pumping sodium ions out of and potassium ions into the cell. Another important example of primary active transport is the proton concentration gradient driven ATP synthesis (Mitchell-hypothesis). 

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