PubMed HealthSearch

PubMed · 5641403

The "pump-leak" model and exchange diffusion.

Abstract

Steady-state concentration gradients across cell membranes have often been attributed to the associated leakage of solute down its electrochemical potential gradient, and active transport at an equal rate in the opposite direction. Several workers have evaluated the minimal energetic requirements of such a "pump-leak" model for sodium in muscle tissue, presuming that influx occurs only via the leak pathway and to no extent by way of the active transport pathway. The high energy requirements so predicted have led to the suggestions that either (a) sodium is not actively transported, being at equilibrium distribution across the cell surface, or (b) substantial sodium movement must be by means of exchange diffusion. The present treatment, based on the consideration that the active transport mechanism is bidirectional, demonstrates that the rates of influx and efflux associated with a given rate of active transport are explicit functions of two parameters: (1) the ratio of the exchange resistance of the active pathway to that of the leak pathway, and (2) the electrochemical potential difference across the cell surface. Lacking precise values for these parameters, the demonstration of a high rate of isotope flux is not compelling evidence either against active transport or for a discrete exchange diffusion mechanism. Various concepts and criteria of exchange diffusion are discussed.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Essig. 1968. The "pump-leak" model and exchange diffusion.. https://doi.org/10.1016/s0006-3495(68)86474-4

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

An NMR study of conformations of substituted dipeptides in dodecylphosphocholine micelles: implications for drug transport.

Efficient transport of intact drug (solute) across the intestinal epithelium is typically a requirement for good oral activity. In general, the membrane permeability of a solute is a complex function of its size, lipophilicity, hydrogen bond potential, charge, and conformation. In conjunction with theoretical/computational and in vitro drug transport studies, seven dipeptide (R(1)-D-Xaa-D-Phe-NHMe) homologues were each dissolved in a micellar d(38)-dodecylphosphocholine solvent system. In this homologous dipeptide series, factors such as size, lipophilicity, hydrogen-bond potential, and charge were either tightly controlled or well-characterized by other methods in order to investigate by nmr how conformational factors relate to transport. Nuclear Overhauser effect spectroscopy experiments and amide-NH-H(2)O chemical exchange rates showed that the five more lipophilic dipeptides were predominately associated with micelle, whereas the two less lipophilic analogues were not. Rotating frame nuclear Overhauser effect spectroscopy derived interproton distance restraints for each analogue, along with (3)J(HH)-derived dihedral restraints, were used in molecular dynamics/simulated annealing computations. Our results suggest that-other factors being equal-flexible dipeptides having a propensity to fold together nonpolar N- and C-terminal moieties allow greater segregation of polar and nonpolar domains and may possess enhanced transport characteristics. Dipeptides that were less flexible or that retained a less amphiphilic conformation did not have comparably enhanced transport characteristics. We suggest that these conformational/transport correlations may hold true for small, highly functionalized solutes (drugs) in general.

Biological Transport, Active

Pulsed high-field gradient in vivo NMR spectroscopy to measure diffusional water permeability in Corynebacterium glutamicum.

Pulsed high-field gradient in vivo NMR spectroscopy was used to measure diffusional water permeability in cell suspensions of the Gram-positive bacterium Corynebacterium glutamicum. Two different regions of H2O mobility were detected. One was characterized by the apparent coefficient of self-diffusion, D(1 app) = (4.6-12.7)x10(-8) cm(2) s(-1), depending on the observation time t. The other region was characterized by D(2) = 1.4x10(-5) cm(2) s(-1). The value of D(2) was similar to the diffusion coefficient of H2O in free water and in extracellular biological fluids. Restricted diffusion could be demonstrated for the slower process (D(1)). It was attributed to the cytoplasm of the cells. The membrane permeability, P(d H2O), for C. glutamicum was (4.8+/-0.4)x10(-3) cm s(-1). It compared favorably with values reported for human erythrocytes and was higher by a factor of about 100 compared to the diffusional permeability for ethanol, P(d ethanol), in Zymomonas mobilis. Addition of HgCl2, a water channel inhibitor in eukaryotes, decreased P(d H2O) in C. glutamicum by a factor of approximately 8. To our knowledge, these are the first functional studies of water transport in prokaryotes that yielded quantitative data, viz., transmembrane water permeability expressed through D(H2O) and P(d H2O).

Biological Transport, Active

Study of vitamin E net mass transfer between alpha-tocopherol-enriched HDL and erythrocytes: application to asymptomatic hypercholesterolemic men.

We previously showed that hypercholesterolemic asymptomatic men had lower erythrocyte vitamin E content, despite normal plasma concentrations compared to normocholesterolemic men. We hypothesized that the reduced erythrocyte vitamin E concentration could be due to an impairment of transfer of vitamin E from plasma lipoproteins. We first developed a model for testing the ability of erythrocytes to accept vitamin E from high-density lipoproteins (HDL) pre-enriched in vitamin E, which allows to measure a net mass transfer of vitamin E from HDL to erythrocytes. Vitamin E-enriched HDL were obtained in controlled conditions of concentration and incubation time with a good reproducibility (CV </= 10%). The kinetic study of the net mass transfer of vitamin E to erythrocytes of healthy volunteers shows small inter- and intraindividual variations. The application of this model to erythrocytes of hyper- and normocholesterolemic men demonstrates that the reduced erythrocyte vitamin E content observed in hypercholesterolemic men was not due to a reduced ability of these cells to accept vitamin E from HDL. It might rather be due to an impairment of lipoproteins in the delivery of vitamin E to tissues, or to an oxidative stress which consumes antioxidants.

Biological Transport, Active