Transporters vectorial

A few cations are transported vectorially into and out of cells, leading to transmembrane concentration gradients. This type of transport, called active transport, is important for H+, Na+, K+, Ca2+ and (possibly) Mg2+. Specific enzymes are found in membranes which couple the hydrolysis of ATP to ion transport, and thereby achieve active pumping21. The activities of humans can seriously affect this type of transport. 

FIGURE 22.21 The mechanism of photophosphorylation. Photosynthetic electron transport establishes a proton gradient that is tapped by the CFiCFo ATP synthase to drive ATP synthesis. Critical to this mechanism is the fact that the membrane-bound components of light-induced electron transport and ATP synthesis are asymmetrical with respect to the thylakoid membrane so that vectorial discharge and uptake of ensue, generating the proton-motive force. 

It is possible that the stationary-state situations leading to an active ion transport occur only in localized regions of the membrane, i.e., at ATPase molecule units with diameters of about 50 A and a length of 80 A. The vectorial ion currents at locations with a mixed potential and special equipotential lines would appear phenomenologically like ionic channels. If the membrane area where the passive diffusion occurs is large, it may determine the rest potential of the whole cell. 

Active Transporters use the energy of ATP for vectorial transport through a biological membrane against concentration gradient of the transported substrate. 

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

The electrochemical potential difFetence across the membrane, once established as a tesult of proton translocation, inhibits further transport of teducing equivalents through the respiratory chain unless discharged by back-translocation of protons across the membtane through the vectorial ATP synthase. This in turn depends on availability of ADP and Pj. 

The physiologically relevant function of the E-IIs is vectorial phosphorylation, i.e., transport with concomitant phosphorylation of the sugar. This reaction requires a phosphoryl group donor, for instance, P-HPr, and it may even be argued that the active species is phosphorylated E-II,... 

Unphosphorylated functioning according to Fig. 5 catalyzes facilitated diffusion of mannitol across the membrane. The same process has been reported for purified II reconstituted in proteoliposomes [70]. The relevance of this activity in terms of transport of mannitol into the bacterial cell is probably low, but it may have important implications for the mechanism by which E-IIs catalyze vectorial phosphorylation. It would indicate that the transmembrane C domain of Il is a mannitol translocating unit which is somehow coupled to the kinase activity of the cytoplasmic domains. We propose that the inwardly oriented binding site which is in contact with the internal water phase (Ecyt Mtl, see Fig. 5) is the site from where mannitol is phosphorylated when transport is coupled to phosphorylation. Meehan-... 

The phosphorylation of cytoplasmic sugar and the facilitated diffusion from the cytoplasm to the periplasm are catalyzed by the E-IIs under conditions where they are also active in the vectorial phosphorylation reaction. Therefore, the former two activities should be integral parts of any kinetic scheme representing the mechanism of E-IIs. Such a scheme should explain how vectorial phosphorylation, transport coupled to phosphorylation, is still achieved while the uncoupled pathways are integral parts of the scheme. 

The rate of the active transport of sodium ion across frog skin depends both on the electrochemical potential difference between the two sides of this complex membrane (or, more exactly, membrane system) and also on the affinity of the chemical reaction occurring in the membrane. This combination of material flux, a vector, and chemical flux (see Eq. 2.3.26), which is scalar in nature, is possible according to the Curie principle only when the medium in which the chemical reaction occurs is not homogeneous but anisotropic (i.e. has an oriented structure in the direction perpendicular to the surface of the membrane or, as is sometimes stated, has a vectorial character). 

Cui, Y., J. Konig, and D. Keppler. Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2, Mol. Pharmacol. 2001, 60, 934—943... 

It is also important to predict the in vivo biliary excretion clearance in humans, and for this purpose MDCK II cell lines expressing both uptake and efflux transporters may be used (Fig. 12.3) [92, 93]. It has been shown that MRP2 is expressed on the apical membrane, whereas OATP2 and 8 are expressed on the basolateral membrane after cDNA transfection (Fig. 12.3) [92, 93]. The transcellular transport across such double-transfected cells may correspond to the excretion of ligands from blood into bile across hepatocytes. Indeed, the vectorial transport from the basal to apical side was observed for pravastatin only in OATP2- and MRP2-expressing... 

The outcome of this is to couple ATP hydrolysis with the vectorial transport of Na+ and K+ across the plasma membrane. The inhibition of the (Na+-K+)-ATPase by cardiac glycosides such as digitalis (an extract of foxglove leaves), which blocks the dephosphorylation of the E2-P form of the enzyme, is the basis for a number of steroid drags which are commonly prescribed for the treatment of congestive heart failure. 

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

In the renal epithelium, many uptake transporters are localized in the basolateral membrane and efflux transporters are localized in the apical membrane (Figure 15.2). As a result, vectorial transport of endogenous substances and of drugs from the blood into the urine is achieved. The important uptake transporters are members of the SLC22 family of solute carriers, especially the family members OCT2 and OAT2, which are highly expressed in human kidney. 

Multidrug Resistance Proteins and Drug Transport 346 Role of P-Glycoprotein for Drug Disposition 349 Vectorial Drug Transport 352 References 355... 

The experiments were continued by Hoffman and Whittam, who concluded that a protein, an ATPase, in the membrane was necessary for active transport and was vectorially organized, with ATP and Na+ being required internally and K+ externally where ouabain was inhibitory. The ATPase was finally identified as the sodium pump by Skou (1957) it vectorially translocated Na+ and K+ across the membrane, and was phosphorylated transiently in the process. 

Koushik KN, Kompella UB (2004) Transport of deslorelin and LHRH agonist is vectorial and exhibits regional variation in excised bovine nasal tissue. J Pharm Pharmacol 56 861-868. 

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