Search PubMed⌕ Search

Biomedical subjects

G F Baker

Publications and source records attributed to G F Baker.

50 records · Page 3Linked to original sources
PubMed1978

Asymmetry of the hexose transfer system in human erythrocytes. Experiments with non-transportable inhibitors.

1. The asymmetrical nature of sugar affinity for the hexose transfer system in human red cells has been demonstrated using purified 4,6-O-ethylidene-alpha-D-glucopyranose (ethylidene glucose) to inhibit the exchange of glucose, 3-O-methyl glucose and galactose. 2. The half-saturation concentration for ethylidene glucose inside the cell is estimated at ca. 110 mM whereas on the outside the value for exchange inhibition is ca 11mM. 3. The asymmetrics of affinities of two related non-transportable inhibitors 1,2-O-isopropylidene-D-glucofuranose and methyl-2,3-di-O-methyl-alpha-D-glucopyranoside have also been studied. 4. From experiments at varying concentrations and on theoretical grounds the half-saturation concentration for non-transportable inhibitors on the outside surface is shown to be over-estimated by measuring inhibition of exchange. In consequence the actual asymmetry of affinities may be greater than observed. 5. Experiments with ethylidene glucose also suggest that conformational changes redistributing components of the hexose transfer system between inward and outward facing modes may occur.

Biological Transport↗
PubMed1973

The permeation of human red cells by 4,6-O-ethylidene- -D-glucopyranose (ethylidene glucose).

1. The glucose derivative 4, 6-O-ethylidene-alpha-D-glucopyranose (ethylidene glucose) was found to inhibit glucose exit competitively but its penetration into human red cells was unaffected by glucose in the medium.2. In penetrating red cells ethylidene glucose followed diffusion type kinetics without any evidence of saturation up to 360 mM. Besides its penetration being unaffected by glucose, 10(-5)M phloretin, which powerfully inhibits the facilitated transfer of hexoses, did not inhibit penetration.3. Red cells incubated with 1-fluoro-2, 4-dinitrobenzene (FDNB) until glucose exit was reduced by 95% showed no slowing of penetration by ethylidene glucose.4. The potentiation of the development of FDNB inhibition by sugars in the incubating medium was absent when ethylidene glucose was used and there was a slight protective action. Cells pre-incubated with 76 mM ethylidene glucose did not show an uphill transfer from 4 mM-[(14)C]glucose in the outside medium in contrast to cells pre-incubated in 76 mM glucose or in 76 mM 3-O-methyl glucose.5. The possibility that ethylidene glucose penetrated human red cells by simple diffusion was supported by its penetration of guinea-pig red cells at similar rates, by the occurrence of osmotic haemolysis in isosmotic solutions which was unaffected by copper ions and by the relatively high ether/water partition of the compound.

Animals↗
PubMed1973

The asymmetry of the facilitated transfer system for hexoses in human red cells and the simple kinetics of a two component model.

1. 4, 6-O-Ethylidene-alpha-D-glucopyranose (ethylidene glucose) has been used to study the competitive inhibition of glucose exchange fluxes when the reagent was (i) inside the cells and (ii) on the outside.2. 50% inhibition of glucose exchange at 20 mM and 16 degrees C required 200 mM ethylidene glucose when on the inside in contrast to 25-30 mM when on the outside.3. The inhibitions at different inhibitor/glucose concentration ratios were measured and analysis of the data suggested that the half-saturation constant for ethylidene glucose was 6 times that for glucose inside the cell as against 1.5 outside. The analysis, however, suggested an asymmetry in respect to the affinities for glucose of approximately ten-fold and this would make the asymmetry towards ethylidene glucose forty-fold.4. Such asymmetries make it necessary to consider a transfer mechanism for sugars with different components on the outer and inner membrane interfaces and simple kinetics for a two component system have been developed and used for analysing the experimental data quantitatively.5. The kinetic similarities to and difference from the kinetics of a simple mobile carrier and those of some more recent models are briefly discussed.

Biological Transport, Active↗
PubMed1973

Further effects of chlorpromazine on the hexose permeability of the human erythrocyte.

1. The effect of chlorpromazine on hexose transfer across the human erythrocyte membrane was investigated by optical and isotopic techniques in intact erythrocytes.2. Chlorpromazine produces two phases of inhibition of glucose exit at 17 degrees C in both types of experiment.3. Glucose exchange flux shows a much smaller decrease in flux rate at the same concentrations of chlorpromazine at 17 degrees C.4. Sorbose and glucose entry at 36 degrees C show a similarly complex inhibition by chlorpromazine. The inhibitor constant (K(i)) for these effects with the two sugars is similar.5. An Arrhenius plot shows that the average energy change for the reaction of the carrier with chlorpromazine is -46 kJ mole(-1) and suggests that a drug-induced conformational change in the carrier may occur.6. These findings require models of hexose permeation to contain separate terms in their kinetics for net and exchange fluxes and the predictions of one such model have been compared with the experimental results.

Biological Transport, Active↗