Vesicle across

The structure of the blood capillary wall is complex and varies in different organs and tissues. It consists of a single layer of endothelial cells joined together by intercellular junctions. Each endothelial cell, on an average, is 20-40 pm long, 10-15 pm wide, and 0.1-0.5 pm thick, and contains 10,000-15,000 uniform, spherical vesicles called plasmalemmal vesicles. These vesicles range in size between 60 and 80 nm in diameter. About 70% of these vesicles open on the luminal side of the endothelial surface, and the remaining open within the cytoplasm. Plasmalemmal vesicles are believed to be involved in the pinocytic transport of substances across the endothelium. The transition time of pinocytic vesicles across the cell is... 

Figure 4.6 Likely mechanisms by which macromolecules cross cellular barriers in order to reach the bloodstream from (in this case) the lung. Transcytosis entails direct uptake of the macromolecule at one surface via endocytosis, travel of the endosome vesicle across the cell, with subsequent release on the opposite cell face via exocytosis. Paracellular transport entails the passage of the macromolecules through leaky tight junctions found between some cells...

Adsorptive) transcytosis a mechanism for transcellular transport in which a cell encloses extracellular material in an invagination of the cell membrane to form a vesicle, then moves the vesicle across the cell to eject the material through the opposite cell membrane by the reverse process. 

Transmission across the cleft is effected by the release of minute quantities of a chemical transmitter (stored in synaptic vesicles) across the presynaptic membrane into the synaptic space from which the transmitter can then interact with the postsynaptic membrane by binding to receptors on it. As impulse is then set up for electrical conduction along the fiber. Impulses generally travel in only one direction—from presynaptic to postsynaptic cells. However, a given nerve fiber can conduct impulses in either direction if, for example, it is electrically stimulated in the middle. 

Smallpox can be transmitted by inhalation of the virus suspended in aerosols. After about a 12-day incubation period, infection from smallpox causes fever and headache. As the virus spreads to the skin it forms pus-filled vesicles across the body. Survivors usually are noticeably scarred for life. The mortality rate for immunized individuals is approximately 3 percent, while for non-immunized humans it increases to 30 percent. 

Consider a phospholipid vesicle containing 10 mMNa ions. The vesicle is bathed in a solution that contains 52 mMNa ions, and the electrical potential difference across the vesicle membrane Ai/t = i/toutskie / inside = —30 mV. What is the electrochemical potential at 25°C for Na ions ... 

When light-driven proton pumping across the thylakoid membrane occurs, a concomitant efflux of Mg ions from vesicles into the stroma is observed. This efflux of Mg somewhat counteracts the charge accumulation due to H ... 

A number of studies have focused on D-A systems in which D and A are either embedded in a rigid matrix [103-110] or separated by a rigid spacer with covalent bonds [111-118], Miller etal. [114, 115] gave the first experimental evidence for the bell-shape energy gap dependence in charge shift type ET reactions [114,115], Many studies have been reported on the photoinduced ET across the interfaces of some organized assemblies such as surfactant micelles [4] and vesicles [5], wherein some particular D and A species are expected to be separated by a phase boundary. However, owing to the dynamic nature of such interfacial systems, D and A are not always statically fixed at specific locations. 

Vacuolar-type proton translocating ATPase is a heter-eomeric protein complex, which appears to translocate two protons across the vesicle membrane for each ATP molecule that is hydrolyzed, generating chemical (ApH) and electrical (A ) gradients. Although the ATPases present on different classes of intracellular vesicle have... 

The exocytotic release of neurotransmitters from synaptic vesicles underlies most information processing by the brain. Since classical neurotransmitters including monoamines, acetylcholine, GABA, and glutamate are synthesized in the cytoplasm, a mechanism is required for their accumulation in synaptic vesicles. Vesicular transporters are multitransmembrane domain proteins that mediate this process by coupling the movement of neurotransmitters to the proton electrochemical gradient across the vesicle membrane. 

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

Other small monomeric GTPases (eg, ARF, Rab, Ras, and Rho) are important in various cellular processes such as vesicle formation and transport (ARF and Rab see below), cettain growth and differentiation processes (Ras), and formation of the actin cytoskele-ton. A process involving GTP and GDP is also crucial in the ttanspott of ptoteins across the membrane of the ER (see below). 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

Reserpine irreversibly inhibits the triphosphatase that maintains the proton gradient and so it depletes neurons of their vesicular store of transmitter. This explains why restoration of normal neuronal function rests on delivery of new vesicles from the cell bodies. Some amphetamine derivatives, including methylenedioxymethamphetamine (MDMA), are also substrates for the transporter and, as a result, competitively inhibit noradrenaline uptake. Another way of inhibiting the transporter is by dissipation of the pH gradient across the vesicular membrane i-chloroamphetamine is thought to act in this way. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

An attractive way to overcome this problem is to use microheterogeneous photocatalytic systems based on lipid vesicles, i.e. microscopic spherical particles formed by closed lipid or surfactant bilayer membranes (Fig. 1) across which it is possible to perform vectorial photocatalytic electron transfer (PET). This leads to generation of energy-rich one-electron reductant A" and oxidant D, separated by the membrane and, thus, unable to recombine. As a result of such PET reactions, the energy of photons is converted to the chemical energy of spatially separated one electron reductant tmd oxidant. 

Fig.3. Mechanism of PET across a lipid membrane, coupled with H2 evolution in EDTA-Ru(bipy) j -V -Pd / lipid vesicle system.

Although several allelochemicals (primarily phenolic acids and flavonoids) have been shown to inhibit mineral absorption, only the phenolic acids have been studied at the physiological and biochemical levels to attempt to determine if mineral transport across cellular membranes can be affected directly rather than indirectly. Similar and even more definitive experiments need to be conducted with other allelochemicals that are suspected of inhibiting mineral absorption. Membrane vesicles isolated from plant cells are now being used to elucidate the mechanism of mineral transport across the plasma membrane and tonoplast (67, 68). Such vesicle systems actively transport mineral ions and thus can serve as simplified systems to directly test the ability of allelochemicals to inhibit mineral absorption by plant cells. 

Since soy lecithin ( 20% extract from Avanti) was selected as a basis for absorption modeling, and since 37 % of its content is unspecified, it is important to at least establish that there are no titratable substituents near physiological pH. Asymmetric triglycerides, the suspected unspecified components, are not expected to ionize. Suspensions of multilamellar vesicles of soy lecithin were prepared and titrated across the physiological pH range, in both directions. The versatile Bjerrum plots (Chapter 3) were used to display the titration data in Fig. 7.33. (Please note the extremely expanded scale for %.) It is clear that there are no ionizable groups... 

Biegel, C. M. Gould, J. M., Kinetics of hydrogen ion diffusion across phospholipid vesicle membranes, Biochemistry 20, 3474-3479 (1981). 

Mucosal brush border membrane vesicles and basolateral membrane vesicles can be isolated to study solute uptake across specific enterocyte boundaries. These more isolated vesicle systems allow for investigation of solute transport across a particular membrane barrier and permit separation of membrane trans-... 

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