Influx carriers

Parry G, Marchant A, May S, Swarup R, Swarup K, James N, Graham N, Allen T, Martucci T, Yemm A, Napier R, Manning K, King G, Bennett M. 2004. Quick on the uptake Characterization of a family of plant auxin influx carriers. J Plant Growth Regul 20 217-225. 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

Like Complex III of mitochondria, cytochrome b6f conveys electrons from a reduced quinone—a mobile, lipid-soluble carrier of two electrons (Q in mitochondria, PQb in chloroplasts)—to a water-soluble protein that carries one electron (cytochrome c in mitochondria, plastocyanin in chloroplasts). As in mitochondria, the function of this complex involves a Q cycle (Fig. 19-12) in which electrons pass, one at a time, from PQBH2 to cytochrome bs. This cycle results in the pumping of protons across the membrane in chloroplasts, the direction of proton movement is from the stromal compartment to the thylakoid lumen, up to four protons moving for each pair of electrons. The result is production of a proton gradient across the thylakoid membrane as electrons pass from PSII to PSI. Because the volume of the flattened thylakoid lumen is small, the influx of a small number of protons has a relatively large effect on lumenal pH. The measured difference in pH between the stroma (pH 8) and the thylakoid lumen (pH 5) represents a 1,000-fold difference in proton concentration—a powerful driving force for ATP synthesis. 

These two conditions (Eqs. (4.97) and (4.98)) are usually sufficient for assuming the medium as quiescent in dilute systems in which both cua.s and cda,oo are small. However, in nondilute or concentrated systems the mass transfer process can give rise to a convection normal to the surface, which is known as the Stefan flow [Taylor and Krishna, 1993]. Consider a chemical species A which is transferred from the solid surface to the bulk with a mass concentration cua.oo- When the surface concentration coa,s is high, and the carrier gas B does not penetrate the surface, then there must be a diffusion-induced Stefan convective outflux, which counterbalances the Fickian influx of species B. In such situations the additional condition for neglecting convection in mass transport systems is [Rosner, 1986]... 

Troutman MD, Thakker DR. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells. Pharm Res 2003 20(8) 1192-1199. 

We note first that immediately following the injection of a sample at the head of the channel, the flow of carrier is stopped briefly to allow time for the sample particles to accumulate near the appropriate wall. As the particles concentrate near the wall, the growing concentration gradient leads to a diffusive flux which counteracts the influx of particles. Because channel thickness is small (approximately 0.25 mm), these two mass transport processes quickly balance one another, leading to an equilibrium distribution near the accumulation wall. This distribution assumes the exponential form... 

Resistance Nonproliferating cells are resistant to methotrexate. Resistance in neoplastic cells can be due to amplification (production of additional copies) of the gene that codes for dihydrofolate reductase resulting in increased levels of this enzyme. The enzyme affinity for MTX may also be diminished. Resistance can also occur from a reduced influx of MTX, apparently caused by a change in the carrier-mediated transport responsible for pumping methotrexate into the cell. 

Thus Kj is the external concentration at which the rate of active uptake is half-maximal—in fact, the observed values of Kj are convenient parameters for describing the uptake of various solutes. If two different solutes compete for the same site on some carrier, JJ1 for species j will be decreased by the presence of the second solute, which is known as competitive inhibition of the uptake of species j. In the case of competitive inhibition, the asymptotic value for the active influx, 7jnmax, is not affected because in principle we can raise c° high enough to obtain the same maximum rate for the active uptake of species j. However, the half-maximum rate occurs at a higher concentration, so the apparent Kj is raised if a competing solute is present that is, is half-maximal at a higher c° when a competitive inhibitor is present (Fig. 3-16a). 

Equation 3.28 describes the competitive binding of solutes to a limited number of specific sites. In other words, active processes involving metabolic energy do not have to be invoked if a solute were to diffuse across a membrane only when bound to a carrier, the expression for the influx could also be Equation 3.28. This passive, energetically downhill entry of a solute mediated by a carrier is termed facilitated diffusion. 

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