Uphill Transport Induced by Counterflow

Abstract

ABSTRACT1. In a membrane transport system containing a mobile carrier with affinities for two substrates a concentration gradient with respect to one of the substrates under certain conditions is able to induce an "uphill" transport (against the concentration gradient) of the other.2. In a kinetic treatment quantitative conditions for such a "flow-induced uphill transport" and some of its characteristics are derived.3. Experimentally the uphill transport of labelled glucose induced by a concentration gradient for rnannose or unlabelled glucose is demonstrated in the human red cell.4. It is shown that the flow-induced uphill transport is a feature characteristic for mobile carrier systems only and is not to be expected in systems in which the substrate is bound to a fixed membrane component ("adsorption membrane"), although such a system may yield identical transport kinetics. Also with respect to Ussing's flux ratio the two systems are different, the adsorption membrane meeting Ussing's criterion, the carrier membrane not.5. It is concluded that the transport system in the human red cells must contain a mobile carrier, identical for glucose and mannose.Through the epithelial cells of kidney (1) and intestine (2) sugars may be transported "actively" in the thermodynamic sense; i.e., against the concentration gradients. Rosenberg (3) has discussed transports of this kind in terms of thermodynamic quantities and potentials. He showed that the mere fact of a transport occurring against the concentration gradient (hereafter termed "uphill") allows the conclusion that a "carrier" in a broader sense is involved in the transport mechanism. In addition, in the case of sugar absorption, other indirect criteria (4) likewise point to carrier mechanisms (limited capacity of the transport, competition, kinetics, effect of enzyme inhibitors).In the erythrocyte, the transport of sugars under conventional experimental * This work was carried out with partial support from the Lalor Fellowship Foundation which is gratefully acknowledged. 289]'.

Structure of, and functional insight into the GLUT family of membrane transporters

“…This was first observed in erythrocytes as uphill hexose counterflow (other terms include countertransport acceleration and trans-stimulation transport). 111,112 In these experiments, hexose was detected flowing apparently against its concentration gradient from the cis side into the trans side of the membrane where hexose is also present, and vice versa. Rosenberg and Wilbrandt argued that the phenomenon was due to two different transport systems present in the red cell, which Naftalin and Holman referred to as a two binding site carrier.…”

Drug transporters in pharmacokinetics

“…Without any molecular knowledge of the carrier proteins themselves, descriptions were made of driving forces for uphill transport such as electrochemical gradients of ions (Heinz 1972;Semenza and Kinne 1985;Alvarado and Van Os 1986), counter-or antiporttransport (Rosenberg and Wilbrandt 1957;Heinz 1978), membrane potential (Ward 1970;Athayde and Ivory 1985) or direct energy transmission due to ATP-cleavage (Caldwell 1956(Caldwell , 1960Keynes 1961;Carafoli and Scarpa 1982). Although it was suggested very early (Sperber 1959), it was later shown that drug excretion and absorption is strongly dominated by membrane carrier proteins, i.e.…”

3‐O‐methylglucose transport in internally dialysed giant axons of Loligo.

“…However, there are some important differences in the way that the squid axon and the human red cell transport sugars. In the human red cell, both glucose uptake and exit are increased when glucose is present at the opposite, trans-side of the membrane P. F. BAKER AND A. CARRUTHERS (Rosenberg & Wilbrandt, 1957;Miller, 1968). In the squid axon, sugar exit is reduced by external sugar and uptake is unaffected by axoplasmic sugar.…”