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Query: UMLS:C0027960 (mole)
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1. Individual capillaries of the transilluminated frog mesentery have been perfused with suspensions of human red cells in frog Ringer solution containing 1-0 g albumin 100 ml.-1. The outer surface of the mesentery has been washed with normal frog Ringer solution and with frog Ringer solutions made hypertonic by addition of one of the following solutes: sodium chloride (100 m-mole. 1.-1); urea (100 m-mole.1.-1); sucrose (20-50 m-mole. 1.-1); cyanocobalamin (8-5 m-mole. 1.-1). The temperature of the mesentery was between 14 and 16 degrees C in all experiments. 2. Wtih the mesentery superfused with normal Ringer, the filtration coefficient was determined from measurements of the rate of fluid filtration across the capillary wall, at a series of known capillary pressures (Michel, Mason, Curry & Tooke, 1974). Filtration coefficient varied from 0-69 X 10(-3) to 4-45 X 10(-3) mum. sec-1 .cm H2O-1 with an average value of 1-87 X 10(-3) mum. sec-1. cm H2O-1. 3. When the superfusate was made hypertonic by the addition of a test solute, the osmotic reflextion coefficient (sigma) of the capillary wall to test solute was calculated from the additional rate of filtration, the concentration of test solute in the superfusate and the filtration coefficient. Average values for sigma were: sodium chloride, 0-068 +/- 0-03 (three capillaries); urea, 0-071 +/- 0.015 (four capillaries); sucrose, 0-115 +/- 0-023 (seven capillaries); cyanocobalamin, 0-100 +/- 0-03 (three capillaries). 4. In further experiments, the osmotic reflextion coefficients to sodium chloride, urea and sucrose were determined in the same capillary. Five technically acceptable experiments were carried out. Although there were differences in the value of sigma between different capillaries, in any one capillary values of sigma were of the same magnitude and there appeared to be no significant trend with the molecular size of the test solute. 5. Our findings are inconsistent with the hypothesis that there is a single pathway for water and small hydrophilic molecules across the capillary wall. 6. Our results may be interpreted in terms of an exclusive channel for water in parallel with a channel shared by both water and small hydrophilic molecules. It is suggested that the exclusive water channel may be the membranes and cytoplasm of the endothelial cells and the shared channel may be located in the intercellular junctions. 7. Our data suggest the exclusive water channel represents about 10% of the total filtration coefficient in frog mesenteric capillaries. The shared channel shows relatively little restriction to the molecules investigated. Estimates of the volume flow throught the two channels are made for conditions where hydrostatic pressure differences and osmotic pressure differences are the driving forces.
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PMID:Osmotic reflextion coefficients of capillary walls to low molecular weight hydrophilic solutes measured in single perfused capillaries of the frog mesentery. 108 61

In this paper we compare the water-transport properties of Aquaporin (AQP1), a known water channel, and those of the 28 kD Major Intrinsic Protein of Lens (MIP), a protein with an undefined physiological role. To make the comparison as direct as possible we measured functional properties in Xenopus laevis oocytes injected with cRNAs coding for the appropriate protein. We measured the osmotic permeability, Pf, (using rate of swelling) and the surface density of plasma membrane proteins (using freeze-fracture electron microscopy) in the same oocytes. Knowing both Pf and the number of exogenously expressed proteins in the membrane, we estimated the single-molecule permeability to be 2.8 x 10(-16) cm3/sec for MIP and 1.2 x 10(-14) cm3/sec for AQP1. As a negative control, a mutant MIP, truncated at the carboxyl-terminal, was shown by western blotting to be expressed, but this protein resulted in no increase in either water permeability or particle density. (Interestingly, the truncated protein was glycosylated, while the complete MIP transcript was not.) Water transport by MIP had a higher activation energy (approximately 7 Kcal/ mole) than water transport by AQP1 (approximately 2.5 Kcal/Mole) but a substantially lower activation energy than water flux across bare oolemma (approximately 20 Kcal/mole). Though the water-transport properties of MIP and AQP1 differ quantitatively, they are qualitatively quite similar. We conclude that MIP, like AQP1, forms water channels when expressed in oocytes. Thus water transport in the lens seems a plausible physiological role for MIP.
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PMID:Comparison of the water transporting properties of MIP and AQP1. 930 8

Aquaporins (AQP) were originally regarded as plasma membrane channels that are freely permeated by water or small uncharged solutes but not by ions. Unlike other aquaporins, AQP6 overexpressed in Xenopus laevis oocytes was previously found to exhibit Hg2+ or pH-activated ion conductance. AQP6 could not be analyzed electrophysiologically in mammalian cells, however, because the protein is restricted to intracellular vesicles. Here we report that addition of a green fluorescence protein (GFP) tag to the N terminus of rat AQP6 (GFP-AQP6) redirects the protein to the plasma membranes of transfected mammalian cells. This permitted measurement of rapid, reversible, pH-induced anion currents by GFP-AQP6 in human embryonic kidney 293 cells. Surprisingly, anion selectivity relative to Cl- revealed high nitrate permeability even at pH 7.4; P(NO3)/P(Cl) > 9.8. Site-directed mutation of a pore-lining threonine to isoleucine at position 63 at the midpoint of the channel reduced NO3-/Cl- selectivity. Moreover, no anomalous mole-fraction behavior was observed with NO3-/Cl- mixtures, suggesting a single ion-binding pore in each subunit. Our studies indicate that AQP6 exhibits a new form of anion permeation with marked specificity for nitrate conferred by a specific pore-lining residue, observations that imply that the primary role of AQP6 may be in cellular regulation rather than simple fluid transport.
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PMID:Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. 1217 1

The mechanism of DNA cytosine-5-methylation catalyzed by the bacterial M.HhaI enzyme has been considered as a stepwise nucleophilic addition of Cys-81-S- to cytosine C6 followed by C5 nucleophilic replacement of the methyl of S-adenosyl-L-methionine to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine. In this study, we show that the reaction is concerted from a series of energy calculations by using the quantum mechanical/molecular mechanical hybrid method. Deprotonation of 5-methyl-6-Cys-81-S-5,6-dihydrocytosine and expulsion of Cys-81-S- provides the product DNA 5-methylcytosine. A required base catalyst for this deprotonation is not available as a member of the active site structure. A water channel between the active site and bulk water allows entrance of solvent to the active site. Hydroxide at 10(-7) mole fraction (pH = 7) is shown to be sufficient for the required catalysis. We also show that Glu-119-CO2H can divert the reaction by protonating cytosine N3 when Cys-81-S- attacks cytosine, to form the 6-Cys-81-S-3-hydrocytosine. The reactants and 6-Cys-81-S-3-hydrocytosine product are in rapid equilibrium, and this explains the observed hydrogen exchange of cytosine with solvent.
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PMID:The mechanism of M.HhaI DNA C5 cytosine methyltransferase enzyme: a quantum mechanics/molecular mechanics approach. 1660 28