Transport processes, inhibition

Chromatin condensation membrane blebbing release of cytochrome c through the permeability transition pore complex activation of caspases Disruption of cytoplasmic membrane and other organelles (e.g., lysosomes, Golgi apparatus) drastic alteration of transmembrane transport processes inhibition of protein synthesis... 

ATPase also catalyzed a passive Rb -Rb exchange, the rate of which was comparable to the rate of active Rb efflux. This suggested that the K-transporting step of H,K-ATPase is not severely limited by a K -occluded enzyme form, as was observed for Na,K-ATPase. Skrabanja et al. [164] also described the reconstitution of choleate solubilized H,K-ATPase into phosphatidylcholine-cholesterol liposomes. With the use of a pH electrode to measure the rate of H transport they observed not only an active transport, which is dependent on intravesicular K, but also a passive H exchange. This passive transport process, which exhibited a maximal rate of 5% of the active transport process, could be inhibited by vanadate and the specific inhibitor omeprazole, giving evidence that it is a function of gastric H,K-ATPase. The same authors demonstrated, by separation of non-incorporated H,K-ATPase from reconstituted H,K-ATPase on a sucrose gradient, that H,K-ATPase transports two protons and two ions per hydrolyzed ATP [112]. 

Anandamide is inactivated in two steps, first by transport inside the cell and subsequently by intracellular enzymatic hydrolysis. The transport of anandamide inside the cell is a carrier-mediated activity, having been shown to be a saturable, time- and temperature-dependent process that involves some protein with high affinity and specificity for anandamide (Beltramo, 1997). This transport process, unlike that of classical neurotransmitters, is Na+-independent and driven only by the concentration gradient of anandamide (Piomelli, 1998). Although the anandamide transporter protein has not been cloned yet, its well characterized activity is known to be inhibited by specific transporter inhibitors. Reuptake of 2-AG is probably mediated by the same facilitating mechanism (Di Marzo, 1999a,b Piomelli, 1999). 

A number of transport mediators are transport proteins in the absence of an external energy supply, thermal motion leads to their conformational change or rotation so that the transported substance, bound at one side of the membrane, is transferred to the other side of the membrane. This type of mediator has a limited number of sites for binding the transported substance, so that an increase in the concentration of the latter leads to saturation. Here, the transport process is characterized by specificity for a given substance and inhibition by other transportable substances competing for binding sites and also by various inhibitors. When the concentrations of the transported substance are identical on both sides of the membrane,... 

Two distinguishing features of gastrointestinal active and facilitated transport processes are that they are capacity-limited and inhibitable. Passive transcellular solute flux is proportional to mucosal solute concentration (C), where the proportionality constant is the ratio of the product of membrane diffusion coefficient (Dm) and distribution coefficient (Kd) to the length of the transcellular pathway (Lm). 

The answers are 321-cT 322-e, 323-i. (Hardman, pp 238-239, 791.) Reserpine is an adrenergic neuronal blocking agent that causes depletion of central and peripheral stores of NE and dopamine Reserpine acts by irreversibly inhibiting the magnesium-dependent ATP transport process that functions as a carrier for biogenic amines from the cytoplasm... 

Mercury can influence ion, water, and nonelectrolyte transport in different cells [ 14, 77]. The cell membrane is believed to be the first point of attack by heavy metals however, intracellular enzymes and metabolic processes may also be inhibited [70, 78, 79]. The attachment of heavy metals to ligands in or on the plasma membrane may result in changes in passive permeability or selective blockage of specific transport processes. Many membrane transport systems are known to be sensitive to sulphydryl-group modification [ 14, 80, 81]. 

There has also been a report regarding the active transport of antibacterial agents in oral mucosa. In a cell line derived from oral epithelium, the uptake of ciprofloxacin and minocycline was not only saturable and inhibited in the presence of other compounds, but the intracellular levels of both antibiotics were 8 10-fold higher than the extracellular levels as well, demonstrating an active transport process [18]. Whether the permeability of these compounds across the entire oral mucosa occurs via an active transport process, however, remains to be determined. 

At the cellular level, plant secondary metabolites have five major effects on herbivores (a) alteration of DNA replication, RNA transcription, and protein synthesis (b) alteration of membrane transport processes (c) enzyme inhibition and activation (d) blocking of receptor sites for endogenous chemical transmitters and (e) affecting the conformation of other macromolecules (Robinson, 1979). 

Hydroxamic acids are important bioligands and are involved in numerous biological processes including metal-ion transport and inhibition of metalloenzymes . 1 1 Metal binding to hydroxamic acids usually occurs in a bidentate fashion (Scheme 99) with... 

I. values ranged between 1 and 20 mM. The compounds did not act as uncouplers or directly inhibit ATP synthesis. However, naringenln, some of the flavones, and the clnnamates acids inhibited th hydrolysis of ATP catalyzed by mitochondrial Mg -ATPase. The Inhibition of substrate oxidation appears to result from alterations and perturbations induced in the inner membrane as evidenced by Interference with carrier-mediated transport processes. 

Transport systems. Partitioning of various types of molecules such as allelochemlcals into the lipid bilayer of the mitochondrial inner membrane can perturb the membrane and alter the conformation, properties, and function of components of the membranes. Unfortunately, it is not always possible to demonstrate directly the existence of carrier systems, but indirect evidence can be obtained. Alterations induced to the membrane are sometimes reflected in the osmotic behavior of mitochondria. The inner membrane is relatively impermeable to many cations, including K and H, and many solutes (31). Hence, the organelles are osmotic-ally stable under certain conditions. Indications were obtained that the allelochemlcals inhibited the action of carrier-mediated transport processes associated with the mitochondrial inner membrane (as reflected in the osmotic behavior). Responses obtained with quercetin are shown in Figure 3. Mitochondria are osmotically... 

The other representative allelochemlcals inhibited the three transport processes much as quercetin did. The concentration ranges at which the allelochemlcals produced interference were similar to those that inhibited whole-chain electron transport. 

The transport process can be inhibited noncompetitively by substances that interfere with cellular metabolism... 

As was stressed by Professor Ubbelohde, in the process of cell recognition not only the lateral diffusion of the binding sites has to be considered, but also the mechanical effects resulting from the local change of surface tension, inducing convection at the cell surface. It is well known, in the cell-to-cell contact inhibition of motion, in tissue culture, that a cell approaches another cell by touching it by means of microvilli and that this process can be affected when adding surfactants to the culture. Now the point is, What is the relative importance of both diffusion and convection Well, in binary surface films, it was observed that the transport process induced by two-dimensional convection is much more rapid than the two-dimensional diffusion. 

An increase of intracellular adenosine levels can also be achieved by inhibition of nucleoside transport proteins. Mammalian nucleoside transport processes can be classified into two types on the basis of their thermodynamic properties. These classes are the concentrative, Na+-dependent transport processes and the equilibrative, Na+-independent processes. The corresponding transporters are called CNTs (concentrative nucleoside transporters) and ENTs (equilibrative nucleoside transporters) (Pastor-Anglada and Baldwin, 2001). 

---