Vectorial transport

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

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. 

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. 

Transporters recognize and bind the molecules to be transported and help them to pass through the membrane as a result of a conformational change. These proteins (permeases) are thus comparable with enzymes—although with the difference that they catalyze vectorial transport rather than an enzymatic reaction. Like enzymes, they show a certain affinity for each molecule transported (expressed as the dissociation constant, in mol L ) and a maximum transport capacity (V). 

Figure 1. Reaction cycle showing how ATP hydrolysis and transient formation of a phosphoryl-enzyme intermediate are linked to the vectorial transport of calcium in the sarcoplasmic reticulum.

Vectorial Transport - A Function for Poly-Ubiquitination in Protein Dislocation ... 

There are two kinds of effects of the membrane on the enzyme behavior a specific interaction between the enzyme and the lipid membrane and a nonspecific interaction of the membrane structure by itself on the enzyme kinetics. In the case of ATPase, the enzyme in solution is working in homogeneous and isotropical conditions. At the opposite extreme, in the membrane the enzyme is working under asymmetrical boundary conditions. In the last case there is a coupling between a scalar process and the vectorial transport effect. In conclusion, the effect of the membrane on the enzyme behavior is not only a chemical effect, but also a geometrical one. 

Complex III Ubiquinone to Cytochrome c The next respiratory complex, Complex III, also called cytochrome focx complex or ubiquinone icytochrome c oxidoreductase, couples the transfer of electrons from ubiquinol (QH2) to cytochrome c with the vectorial transport of protons from the matrix to the intermembrane space. The determination of the complete structure of this huge complex (Fig. 19-11) and of Complex IV (below) by x-ray crystallography, achieved between 1995 and 1998, were landmarks in the study of mitochondrial electron transfer, providing the structural framework to integrate the many biochemical observations on the functions of the respiratory complexes. 

Figure 10.3 Vectorial transport of a chemical from the liver sinusoid, through the hepatocyte, to the canalicular space.

Figure 10.5 Processes involved in the vectorial transport of xenobiotics from the whole body point of origin to the specific site of elimination.

Mita S, Suzuki H, Akita H, et al. Vectorial transport of hile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol 2005 288 G15943167. 

The most difficult and interesting question about H+-ATPase is how chemical reaction (ATP synthesis/ hydrolysis) is coupled with vectorial H+ conduction. The mechanism for the stoichiometric coupling between chemical reaction and vectorial transport of ions is a universal question for ion-motive ATPases. The Fo portion is a passive proton pathway but becomes a regulated pathway after the binding of Fi. Mutant analyses suggest that the y subunit has regulatory role(s) for proton conduction. 

Tester, P.A., Turner, J, and Shea, D. 2000. Vectorial transport of toxins from the dinoflagellate Gymnodium breve through copepods to fish. Journal of Plankton Research 22, 47-61. 

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