Transporters interactions mediated

VLDLs, IDLs, and LDLs are closely related to one another. VLDLs formed in the liver (see p. 312) transport triacylglycerols, cholesterol, and phospholipids to other tissues. Like chylomicrons, they are gradually converted into IDL and LDL under the influence of lipoprotein lipase [1]. This process is also stimulated by HDL. Cells that have a demand for cholesterol bind LDL through an interaction between their LDL receptor and ApoB-100, and then take up the complete particle through receptor-mediated endocytosis. This type of transport is mediated by depressions in the membrane ( coated pits"), the interior of which is lined with the protein clathrin. After LDL binding, clathrin promotes invagination of the pits and pinching off of vesicles ( coated vesicles"). The clathrin then dissociates off and is reused. After fusion of the vesicle with ly-sosomes, the LDL particles are broken down (see p. 234), and cholesterol and other lipids are used by the cells. 

Drug interactions mediated by CYP enzymes in the bowel wall, liver, or transporters in the bowel wall... 

Kodawara, T., et al. 2002. Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Pharm Res 19 (6) 738. 

Treiber A, Schneiter R, Delahaye S, et al. Inhibition of organic anion transporting polypeptide-mediated hepatic uptake is the major determinant in the pharmacokinetic interaction between bosentan and cyclosporin A in the rat. J Pharmacol Exp Ther 2004 308 1121-1129. 

It has recently been proposed that the Biopharmaceutical Classification System (BCS) can be used to predict intestinal drug disposition with regards to efflux transport and metabolism (339). Furthermore, on the basis of the key substrate BCS-related properties, permeability, and solubility, the system may be used to predict potential interactions mediated through changes in efflux and/or metabolism at the level of the intestine. 

Liu, J., Rone, M. B., and Papadopoulos, V. (2006). Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis. J Biol Chem 281, 38879-38893. 

In molecular terms, the movement of an ion across a membrane via a channel can best be described as a series of "hops" along the stationary channel molecule. The ion-transporter interactions that facilitate ion translocation replace ion-water interactions on either side of the membrane. The energy barrier for direct ion diffusion across the membrane is directly due to the instability of the ion in the nonpolar membrane interior. lon-chatmel interactions significantly lower the barrier and thus facilitate diffusion.A similar argument applies to carrier-mediated transport, with the result that chaimels and carriers are kinetically indistinguishable. However, activation barriers for channel-mediated diffusion are expected to be much lower than the activation barrier for carriers. " with the result that the maximum transport rates of channels are typically several orders of magnitude higher than those of carriers. 

Such long-range interactions pose special challenges to analytic theory and experiment as well as to computer simulations. In the case of the dynamics of neutral chains in solution, the hydrodynamic interaction, mediated by momentum transport through the solvent, falls off with a 1/r power law. This introduces significant changes in the dynamical properties of the chains and consequently the solutions. It does not, however, affect the static properties. Theoretically even the simplest problem of a single... 

Nakanishi, T. Shibue, Y. Fukuyama, Y Yoshida, K. Fukuda, H. Shirasaka, Y Tamai, I. Quantitative time-lapse imaging-based analysis of drug-drug interaction mediated by hepatobiliary transporter, multidrug resistance-associated protein 2, in sandwich-cultured rat hepatocytes. Drug Metab. Dispos. 2011, 39,984-991. 

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