Electrochemical gradient

Peter Mitchell s chemiosmotic hypothesis revolutionized our thinking about the energy coupling that drives ATP synthesis by means of an electrochemical gradient. How much energy is stored in this electrochemical gradient For the transmembrane flow of protons across the inner membrane (from inside [matrix] to outside), we could write... 

Electron tran.sport drive.s out and create.s an electrochemical gradient... 

FIGURE 21.22 The proton and electrochemical gradients existing across the inner mitochondrial membrane. The electrochemical gradient is generated by the transport of protons across the membrane. 

The thylakoid membrane is asymmetrically organized, or sided, like the mitochondrial membrane. It also shares the property of being a barrier to the passive diffusion of H ions. Photosynthetic electron transport thus establishes an electrochemical gradient, or proton-motive force, across the thylakoid membrane with the interior, or lumen, side accumulating H ions relative to the stroma of the chloroplast. Like oxidative phosphorylation, the mechanism of photophosphorylation is chemiosmotic. 

The mechani.sm of photopho.sphorylation i.s chemio.smotic. In 1966, Jagendorf and Uribe experimentally demon.strated for the first time drat establishment of an electrochemical gradient across the membrane of an energy-tran.sdncing organelle conld lead to ATP. synthe.sis. They equilibrated isolated chloroplasts for 60 seconds in a pH 4 bath, adjusted die pH to 8 in die presence of ADP and Pi, and allowed phosphorylation to proceed for 15 seconds. The entire experiment was carried ont in tire dark. 

Permeation of a drug through biological membranes against the electrochemical gradient. This type of drug transport requires energy produced by intracellular metabolic processes. 

Voltage-gated Ca2+ channels are Ca2+-selective pores in the plasma membrane of electrically excitable cells, such as neurons, muscle cells, (neuro) endocrine cells, and sensory cells. They open in response to membrane depolarization (e.g., an action potential) and permit the influx of Ca2+ along its electrochemical gradient into the cytoplasm. 

Potassium channels are a diverse and ubiquitous family of membrane proteins present in both excitable and nonexcitable cells that selectively conduct K+ ions across the cell membrane along its electrochemical gradient at a rate of 106-108 ions/s. 

Sialin was first identified as the product of the gene defective in sialidosis, a lysosomal storage disorder. The transporter mediates the movement of sialic acid out of lysosomes by coupling to the proton electrochemical gradient across the lysosomal membrane. Unlike the vesicular neurotransmitter transporters which are antiporters, sialin is a sympoiter with sialic acid and protons both moving out of the lysosome. 

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... 

In addition to direct inhibition of the vesicular transport protein, storage of neurotransmitters can be reduced by dissipation of the proton electrochemical gradient. Bafilomycin (a specific inhibitor of the vacuolar H+-ATPase), as well as the proton ionophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and carbonylcyanide p-(trifluoromethoxy) phenylhy-drazone (FCCP) are used experimentally to reduce the vesicular storage of neurotransmitters. Weak bases including amphetamines and ammonium chloride are used to selectively reduce ApH. 

The sodium channels are very selective for Na+ over K+, allowing Na+ influx down the electrochemical gradient to generate positive membrane potentials. The sodium channels are also permeable to Li+ and NH4+. The narrowest portion of the channel pore is estimated to be rectangular (3.1 x 5.2 A). 

Voltage-gated potassium (Kv) channels are membrane-inserted protein complexes, which form potassium-selective pores that are gated by changes in the potential across the membrane. The potassium current flow through the open channel follows by the electrochemical gradient as defined by the Nernst equation. In general, Kv channels are localized in the plasma membrane. 

Proton electrochemical gradient. 6,714 Proton exchange amine ligands, 2, 24 Proton loss catalysis... 

Nicholls, D.G. (1974). The influence of respiration and ATP hydrolysis on the proton electrochemical gradient across the inner membrane of rat liver mitochondria as determined by ion distribution. Eur. J. Biochem. 50,305-315. 

Membrane depolarization can be measured by members of a class of fluorophores (commonly referred to as the carbocyanine dyes) which have been designed to partition into the membrane, where their orientation and spectral properties change with changes in the electrochemical gradient across the membrane (18). 3,3 -dipropyl-... 

Energy-linked transhydrogenase, a protein in the inner mitochondrial membrane, couples the passage of protons down the electrochemical gradient from outside to inside the mitochondrion with the transfer of H from intramitochondrial NADH to NADPH for intramitochondrial enzymes such as glutamate dehydrogenase and hydroxylases involved in steroid synthesis. 

Because the inner mitochondrial membrane is impermeable to protons and other ions, special exchange transporters span the membrane to allow passage of ions such as OH, Pf, ATP , ADP, and metabo-htes, without discharging the electrochemical gradient across the membrane. 

Molecules can passively traverse the bilayer down electrochemical gradients by simple diffusion ot by facilitated diffusion. This spontaneous movement toward equilibrium contrasts with active transport, which requires energy because it constitutes movement against an electrochemical gradient. Figure 41-8 provides a schematic representation of these mechanisms. 

As described above, some solutes such as gases can enter the cell by diffusing down an electrochemical gradient across the membrane and do not require metabolic energy. The simple passive diffusion of a solute across the membrane is limited by the thermal agitation of that specific molecule, by the concentration gradient across the membrane, and by the solubility of that solute (the permeability coefficient. Figure 41—6) in the hydrophobic core of the membrane bilayer. Solubility is... 

Some specific solutes diffuse down electrochemical gradients across membranes more rapidly than might be expected from their size, charge, or partition coefficients. This facilitated diffusion exhibits properties distinct from those of simple diffusion. The rate of facilitated diffusion, a uniport system, can be saturated ie, the number of sites involved in diffusion of the specific solutes appears finite. Many facihtated diffusion systems are stereospecific but, fike simple diffusion, require no metabolic energy. 

The thyroid is able to concentrate T against a strong electrochemical gradient. This is an energy-dependent process and is linked to the Na -K ATPase-dependent thyroidal T transporter. The ratio of iodide in thyroid to iodide in serum (T S ratio) is a reflection of the activity of this transporter. This activity is primarily controlled by TSH and ranges from 500 1 in animals chronically stimulated with TSH to 5 1 or less in hy-pophysectomized animals (no TSH). The T S ratio in humans on a normal iodine diet is about 25 1. 

Uptake of noradrenaline into the vesicles depends on an electrochemical gradient driven by an excess of protons inside the vesicle core. This gradient is maintained by an ATP-dependent vesicular H+-triphosphatase. Uptake of one molecule of noradrenaline into the vesicle by the transporter is balanced by the counter-transport of two H+ ions (reviewed by Schuldiner 1998). It is thought that either binding or translocation of one H+ ion increases the affinity of the transporter for noradrenaline and that binding of the second H+ actually triggers its translocation. 

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