Vacuum cleaner model

Several mechanistic models have also been proposed to elucidate how the P-gp transporter translocates substrates across cellular membranes. In the vacuum cleaner model, which seems the most probable, the compounds partition into the membrane bilayer and then P-gp extracts the substrates from the inner (cytosolic) membrane leaflet and releases them through a protein channel into the extracellular medium (Figure 16.1) [7,14,17]. 

Figure 16.1 Schematic representation of a vacuum cleaner model drug partitions into the membrane bilayer, flips across the lipid core, accesses the TMDs from the inner membrane leaflet and is released through a protein channel into the extracellular medium.

Fig. 9.15. Proposed mechanism by which P-glycoprotein (P-gp) secretes substrates. (1) Passive drug uptake across cell membrane. (2a) Formation of hydrophobic channel (pore) between the intracellular and extracellular space. (2b) Flippase activity, whereby the drug is flipped from the inner leaflet to the outer leaflet of the cell membrane. (2c) Vacuum cleaner model, in which drug interacts with P-gp in the lipid bilayer and is subsequently secreted back into the extracellular space. (From Matheney C, Lamb M, Brouwer K, et al. Pharmacokinetics and pharmacodynamic implications of P-glycoprotein modulation. Reviews of Therapeutics 2001 21 778-796 with permission.)...

Figure 9.35 Three proposed models of P-gp drug efflux, (a) The pore model, in which cytosolic drug is transported through a protein channel, (b) the flippase model, where drug associated with the inner leaflet of the membrane bilayer is flipped into the onter leaflet where it might passively diffuse out of the cell, and, (c) the hydrophobic vacuum cleaner model, where drug associated with the inner leaflet of the bilayer is exported out through the protein. (Reprinted with permission from Varma, M.V.S., et al. P-glycoprotein inhibitors and their screening A perspective from bioavailability enhancement. Pharmacol. Res. 2003, 48, 347-359, copyright 2003, Elsevier).

Two models have been developed to describe P-gp s unique transport activity. Higgins and Gottesman have postulated that P-gp acts as a hydrophobic vacuum cleaner, clearing the plasma membrane of substrates before they enter... 

Have a good look at a vacuum cleaner filter, try to find or measure its technical parameters and make a quantitative model of its behaviour. 

My son s early model Speak Spell had given him what seemed to be hundreds of hours of enjoyment when one day the enter key broke off at its plastic hinge. But since Stephen could still fit his small finger into the buttonhole to activate the switch, he continued to enjoy the smart, if disfigured, toy. Soon thereafter, however, the E key snapped off, and soon the T and O keys followed suit. Although he continued to use the toy, its keyboard soon became a maze of missing letters and, for those that were saved from the vacuum cleaner, taped-on buttons. 

Designed for fine or difficult powders, VAC-U-MAX Model llOMFS portable industrial vacuum cleaner has 80 percent more suction power than most other vacuums in the 5HP class. It features a standard PTFE leaf-style filter rated 99.9 percent and has an aggressive manual filter shaker that prevents filter blinding. VAC-U-MAX, www.vac-u-max.com,... 

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