Plasma membrane transporter

Fructose is present outside a cell at 1 /iM concentration. An active transport system in the plasma membrane transports fructose into this cell, using the free energy of ATP hydrolysis to drive fructose uptake. Assume that one fructose is transported per ATP hydrolyzed, that ATP is hydrolyzed on the intracellular surface of the membrane, and that the concentrations of ATP, ADP, and Pi are 3 mM, 1 mM, and 0.5 mM, respectively. T = 298 K. What is the highest intracellular concentration of fructose that this transport system can generate Hint Kefer to Chapter 3 to recall the effects of concentration on free energy of ATP hydrolysis.)... 

In addition to secretory cells, many non-secretory cells are capable of regulating exocytotic fusion of transport vesicles that are derived from endosomal precursors. For instance, vesicles enriched in plasma membrane transport proteins are incorporated in a regulated manner in order to alter metabolite fluxes. Examples include the glucose transporter GLUT-4 in muscle and fat tissues, a key element in the control of... 

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... 

Garcia Ruiz, C., Fernandez Checa, J. and Kaplowitz, N. (1992). Bidirectional mechanism of plasma membrane transport of reduced glutathione in intact rat hepatocytes and membrane vesicles. J. Biol. Chem. 267, 2256-2264. 

F. G. M. Maathuis. and D. Sanders, Plasma membrane transport in context—making. sense out of complexity, Curr. Opin. Plant Biol. 2 236 (1999). 

P-glycoprotein, a plasma membrane transport protein, is present in the gut, brain, liver, and kidneys 42 This protein provides a biologic barrier by eliminating toxic substances and xenobiotics that may accumulate in these organs. P-glycoprotein plays an important role in the absorption and distribution of many medications. Medications that are CYP3A4 substrates, inhibitors, or inducers are also often affected by P-glycoprotein therefore, the potential for even more DDIs exists in transplant recipients.42... 

Following the release of dopamine, the primary mode of removal from the synapse is reuptake into the presynaptic neuron via the dopamine transporter (DAT). DAT is dependent upon the energy created by the Na+/K+ pump and is a member of the Na+/Cl -dependent plasma membrane transporter family, as are the norepinephrine and 7-aminobutyric acid (GABA) transporters. Imaging studies utilizing compounds with highly specific affinity for DAT... 

Figure 4.5 Fet3p and copper homeostasis. Defects in the plasma membrane transporters Ctrl and Ctr3, the cytosolic copper chaperone Atxlp, or the vesicular copper transporter Ccc2p affect Fet3p activity. Reprinted from Askwith and Kaplan, 1998. Copyright (1998), with permission from Elsevier Science.

Although there are a number of mechanisms in cells for buffering or sequestering Ca2+ to prevent untoward or inappropriate rises in [Ca2+]i( in the long term, it is the activity of plasma membrane transport processes that determines the steady-state [Ca2+]j. This is because the plasma membrane acts as a Ca2+ buffer of essentially infinite capacity. This results from in vivo clamping of the extracellular concentration of Ca2+ by dietary and endocrine mechanisms. In in vitro experiments, this results from incubation volumes very much larger than the cell volume. 

Monoamine-reuptake plasma membrane transporters Monoamine vesicle transporters (VAT)... 

Loeper J, Le Berre A, Pompon D. 1998. Topology inversion of CYP2D6 in the endoplasmic reticulum is not required for plasma membrane transport. Mol Pharmacol 53 408-414. 

Yao SYM, Cass CE, Young JD. 2000. The Xenopus oocyte e3q>ression system for the cDNA cloning and characterization of plasma membrane transport proteins. In Membrane transport A Practical Approach. Baldwin SA, editor. Oxford University Press, Oxford, pp. 47-78. 

As the quantitatively predominant HDL component, apoA-I is crucial for HDL formation. It is also needed to activate LCAT and to mediate the interaction between HDL and cell surface receptors, such as scavenger receptor B1 or plasma membrane transporters such as ABCA1 [42]. Numerous non-sense and missense mutations in the apoA-I gene have been found to interfere with the formation of HDL, and to cause gene-dose-dependent decreases in HDL cholesterol, with a virtual absence of HDL in homozygotes and half-normal levels of HDL cholesterol in heterozygotes [22, 89, 92]. 

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mv 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel. 

Flavonoids can affect the function of plasma membrane transport Na+- and K+-ATPase, mitochondrial ATPase, and Ca2+-ATPase. The Mg2+-ectoATPase of human leukocytes is inhibited by quercetin, which acts as a competitor of ATP binding to the enzyme. The sarcoplasmic reticulum Ca2+-ATPase of muscle is effectively inhibited by several flavonoids that were also active inhibitors of antigen-induced mast cell histamine release. 

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes. There are at least 10 distinct aquaporins in mammals with specific expression patterns in epithelial, endothelial, and other tissues. Studies in aquaporin-null mice indicated a key role for aquaporins in the urinary concentrating mechanism, fluid secretion of glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption.62... 

Plasma membrane transport of thyroid hormone into rat hepatocytes... 

The concept that plasma membrane transport plays a key role in the regulation of intracellular thyroid hormone levels is supported by studies with a monoclonal antibody against an antigen exposed on rat liver cells [107], This antibody inhibited the uptake of different iodothyronines by rat hepatocytes under initial rate conditions as well as the metabolism of these compounds during prolonged incubations [107]. Uptake and metabolism of T4, T3 and rT3 were affected to the same extent, suggesting that a single system operates in the transport of different iodothyronines, which is opposite to the view advanced above. However, it is not excluded that the antibody interacts with a component of the plasma membrane and thereby affects multiple transport systems. 

GSH, glutathione conjugate, and GSSG transport out of most cell types via plasma membrane transporters... 

Ward, J.M. 1997. Patch-clamping and other molecular approaches for the study of plasma membrane transporters demystified. Plant Physiol. 114 1151-1159. 

Although plasma membrane monoamine transporters are responsible for the reuptake of neurotransmitters from the synapse, vesicular monoamine transporters (VMAT) sequester monoamines into synaptic vesicles in preparation for fusion with the plasma membrane and release into the synapse (Schuldiner et ah, 1995). Vesicular uptake is coupled to a proton gradient across the vesicle membrane rather than the sodium gradient used with the plasma membrane transporters (Schuldiner et ah, 1995). These vesicular transporters are not neurotransmitter-speciflc rather, they transport the monoamines nonselectively (Johnson, Jr., 1988 Henry et ah, 1998). 

VMAT is predicted to have similar membrane topology to the plasma membrane monoamine transporters, although they do not share homologous sequences (Erickson et ah, 1992). Hydrophobicity studies predict 12 TMHs with amino and carboxy termini located in the cytoplasm (Erickson et al., 1992). The large extracellular loop between TMHs III and IV of the plasma membrane transporters is located between TMHI and II in VMAT (Erickson et al., 1992). VMATl is located in the neuroendocrine cells of the adrenal medulla and intestinal tract, whereas VMAT2 is found in monoaminergic neurons of the central nervous system (Erickson et al., 1996). 

Donnan GA, Kaczmarczyk SJ, Paxinos G, Chilco PJ, Kalnins RM, Woodhouse DG, Mendelsohn FA (1991) Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography. J Comp Neurol 304 419-434 Eisenhofer G (2(X)1) The role of neuronal tmd extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther 91 35-62... 

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