Reversible transport pathways

Gorodeski GI, Hopfer U, Eckert RL, Utian WH, De-Santis BJ, Rorke ER, and Romero MF [1994] ATP decreases acutely and reversibly transport through the paracellular pathway in human uterine cervical cells. Am J Physiol 266 0 692-0698... 

HDL may be taken up in the liver by receptor-mediated endocytosis, but at least some of the cholesterol in HDL is delivered to other tissues by a novel mechanism. HDL can bind to plasma membrane receptor proteins called SR-BI in hepatic and steroidogenic tissues such as the adrenal gland. These receptors mediate not endocytosis but a partial and selective transfer of cholesterol and other lipids in HDL into the cell. Depleted HDL then dissociates to recirculate in the bloodstream and extract more lipids from chylomicron and VLDL remnants. Depleted HDL can also pick up cholesterol stored in extrahepatic tissues and carry it to the liver, in reverse cholesterol transport pathways (Fig. 21-40). In one reverse transport path, interaction of nascent HDL with SR-BI receptors in cholesterol-rich cells triggers passive movement of cholesterol from the cell surface into HDL, which then carries it back to the liver. In a second pathway, apoA-I in depleted HDL in-... 

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g., buserelin). /V-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the para-cellular transport pathway. The absorption-enhancing effect was concentration dependent and reversible and dependent on the integrity of the intercellular cell contact zone. 

Tangier Disease A Disorder in the Reverse Cholesterol Transport Pathway... 

How would you modulate the reverse cholesterol transport pathway to increase cholesterol efflux from cells in normal individuals ... 

G19. Graham, A., Vinogradov, D. V., and Owen, J. S., Effects of peroxynitrite on plasma components of the reverse cholesterol transport pathway. FEBS Lett. 431, 327-332 (1998). 

The overall reaction is energy yielding, and allows sufficient ATP production to support reverse electron transport for CO2 fixation. However, the first step, oxidation of NH3 to hydroxylamine, requires the input of reducing power. The second step, hydroxylamine oxidation, yields four electrons. These join the electron transport chain at the level of ubiquinone, from which two are shunted back to AMO for activation of NH3. The N oxidation and electron transport pathways in Nitrosomonas are linked in the cytoplasmic membrane and periplasmic space detailed information from the N. europaea genome (Chain et al., 2003) is consistent with the previous biochemical characterizations of the system (Whittaker et al., 2000). Depending on conditions (and enhanced at low oxygen concentrations), nitric oxide (NO), nitrous oxide (N2O) and even dinitrogen gas (N2) have been reported as secondary products... 

HDL, like LDL, is a cholesterol-rich particle, and is distinct from the other lipoprotein classes in that it does not contain apoB. HDL levels are inversely correlated with risk for atherosclerosis (Wilson et al., 1988). Nascent HDL particles are produced by direct synthesis (Hamilton, 1984), and excess surface remnants from chylomicrons and VLDL produced during the action of lipoprotein lipase (as noted above) enter the HDL density class. HDL appears to be involved in delivery of cholesterol to steroidogenic tissues as well as the removal of excess cholesterol from peripheral tissues and excretion from the system. This HDL-mediated removal of cholesterol has been termed reverse cholesterol transport (Glomset, 1968). Although apolipoproteins present in HDLs are cleared by the liver, the reverse cholesterol transport pathway has never been directly demonstrated. HDL can remove cholesterol from tissues, a process that may be partially mediated by interaction with a putative HDL receptor, with apoA-I as the ligand for that receptor (Oram el ai, 1983). The existence of an HDL receptor remains controversial saturable HDL binding may not be mediated by a specific apolipoprotein ligand and may not even be required for transfer of cholesterol from cells to... 

Figure 26-21 Reverse cholesterol transport pathway. HDl High-density lipoproteins LDL, low-density lipoproteins tDL, intermediate-density lipoproteins HTL, hepatic lipoprotein lipase LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein apo E, apoiipoprotein E. Cholesterol is removed from macrophages and other arterial wall cells by an HDL-mediated process. The LCAT esterifies the cholesterol content of HDL to prevent it from reentering the ceils. Cholesterol esters are delivered to the liver by one of three pathways ( ) cholesterol esters are transferred from HDL to LDL by CETP and enter the liver through the specific LDL receptor pathway (2) cholesterol esters are selectively taken from HDL by HDL receptors and HDL particles are returned to circulation for further transport or (3) HDL have accumulated apo E and therefore the particles can enter the liver through remnant receptors, (From Gwynne JT. High density lipoprotein cholesterol levels as a marker of reverse cho/estero/ tronsport./ m j Cardiol I989 64 10G-I7G. Copyright 1989, with permission from Excerpta Medico Inc.)...

HDL is antiatherogenic and removes cholesterol from peripheral cells and tissues for eventual transport to hepatocytes and excretion in the bile directly or after conversion into bile acids. The efflux of cholesterol from peripheral cells is mediated by the ATP-binding cassette (ABC) transporter protein (discussed later). The flux of cholesterol transport from extrahepatic tissues (e.g., blood vessel wall) toward liver for excretion is known as the reverse cholesterol transport pathway. In contrast, the forward cholesterol pathway involves the transport of cholesterol from liver to the peripheral cells and tissues via the VLDL IDL LDL pathway. It should be noted, however, that the liver plays a major role in the removal of these lipoproteins. Thus, the system of reverse cholesterol transport consisting of LCAT, CETP, apo D, and their carrier lipoproteins is critical for maintaining cellular cholesterol homeostasis. The role of CETP is exemplified in clinical studies involving patients with polymorphic... 

Plate 17. Summary of major forward and reverse lipid transport pathways through the extracellular compartment that link the liver and intestine with peripheral tissues. FC, unesterified cholesterol. For other abbreviations see list of abbreviations. (See page 536 in this volume.)... 

Dissolution of the oxidant or reductant during a redox reaction can greatly reduce the reversibility of the system. The dissolution can alter an electrode material from an undissolved state to a dissolved one. In an imdissolved state, it exhibits a controlled three-dimensional morphology that is closely linked to the conductive transport pathways of the current collector. When a redox reaction moves the material into a dissolved state, the charge is lost. Then the process becomes heavily diffusion limited and if the electrode was designed for charging based on its undissolved state, the diffusion will likely generate an overpotential on the material and the capacitance will be irreversible. 

PPARs enhance cholesterol efflux and stimulate critical steps of the reverse cholesterol transport pathway (reviewed in ref. 507). PUFA and activating PPAR increase hepatic cholesterol uptake. PPARy induces expression of SR B1 in rat hepatocytes, liver EC, and Kuppfer cells (508). PPARa activation in human macrophages and foam cells results in an enhanced availability of free cholesterol for efflux through the ABCAl pathway by reducing cholesterol esterification rates and ACATl activity (509). 

Contaminant transfer to bed sediments represents another significant transfer mechanism, especially in cases where contaminants are in the form of suspended solids or are dissolved hydrophobic substances that can become adsorbed by organic matter in bed sediments. For the purposes of this chapter, sediments and water are considered part of a single system because of their complex interassociation. Surface water-bed sediment transfer is reversible bed sediments often act as temporary repositories for contaminants and gradually rerelease contaminants to surface waters. Sorbed or settled contaminants are frequently transported with bed sediment migration or flow. Transfer of sorbed contaminants to bottomdwelling, edible biota represents a fate pathway potentially resulting in human exposure. Where this transfer mechanism appears likely, the biotic fate of contaminants should be assessed. 

The pathways of HDL metabolism and reverse cholesterol transport are complex (Fig. 3, [1]). HDL and its major apolipoprotein apoA-I are synthesized by both the intestine and the liver. A second major... 

Ecyt Mtl followed by dissociation of mannitol at the cytoplasmic side (Ecyt Mtl Ecyt). The reverse pathway would be measured with the binding to the ISO membranes. The small rate constants for the latter two processes indicate that turnover through the cycle as depicted in Fig. 5 is very slow and has to be accelerated considerably when transport is coupled to phosphorylation. 

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