Interaction between Na+-dependent transport systems for sugars and amino acids. Evidence against a role for the sodium gradient

Abstract

Summary. The concept that interaction between sodium-dependent transport systems represents competition for energy inherent in the transmembrane sodium gradient was examined with the use of isolated intestinal epithelial cells. The isolated cells exhibit transport interactions which are more significant in magnitude than those which have been described for intact tissue preparations. Accumulation of 1 mu valine is inhibited 60% by 10 mM 3-OMG. Conversely, uptake of 1 mM 3-OMG is inhibited only 20% by 10 mM valine. These data suggest that 3-OMG must discharge the cellular Na + gradient more effectively than valine, if Na + gradient dissipation can be taken as a basis for the inhibitory interaction. However, entry of 10 mu 3-OMG is significantly slower than the entry of 10 mM valine. Even if appropriate corrections are made for passive substrate entry and for differences in Na/substrate entry stoichiometry, it appears that valine should be somewhat more effective than 3-OMG in discharging the Na + gradient. In light of these facts, it seems unlikely that the mechanistic basis for interaction between sugar and amino acid transport systems can be related to concomitant co-entry of Na +. It is suggested that the interaction results instead from competition for energized intermediates generated at limited rates by basic energy transduction events associated with the cell membrane which serve in support of a variety of active transport systems.

Characteristics of amino acid accumulation by isolated intestinal epithelial cells

“…More significantly, as much as a two-to threefold valine gradient was generated during the first minute of the experiment, when cellular sodium concentration exceeded that in the medium. These gradients are somewhat greater than those observed for sugars within the same interval, and apparently reflect the faster entry rates associated with valine entry [13,14].…”

“…Entry of 1 mM valine in the presence of 25 mM leucine was used as a correction for diffusional entry. This concentration of leucine appears to be sufficient to block carrier-mediated valine entry [13,14]. The difference between the entry rates in the absence of leucine and those observed with 25 mM leucine present was taken as the rate of carrier-mediated entry.…”

“…Co-transport of sodium with substrate is thought to produce a partial discharge of the sodium gradient, which consequently diminishes the transport of any other substrate deriving its energy from the same source [21]. We will examine this premise in detail in one of the following papers [13]. For the present discussion, however, it is important to recognize that there are certain inconsistencies between the work presented here, and predictions derived from a model for interaction based on transport-induced dissipation of the sodium gradient.…”

“…The following two papers consider the role of K § and K § gradients in sugar or amino acid accumulation by the cells, and the significance of the interaction observed between the transport systems for sugars and amino acids [12,13].…”

Effects of dietary intake of sodium chloride on sugar and amino acid transport across isolated hen colon

“…Alvarado (1966) and Robinson & Alvarado (1977) have propagated the idea of allosteric interactions between the binding sites for sugars and amino acids. Newey & Smyth (1964) and Kimmich & Randles (1973) proposed that the available energy was insufficient to provide for optimal, parallel function of the two transport systems. Semenza (1971), Frizzell & Schultz (1971), Murer, Sigrist-Nelson & Hopfer (1975), and Munck (1978) found that mutual inhibition could be abolished by 334 ADAPTATION OF SUGAR AND AMINO ACID TRANSPORT 335 reducing or eliminating the Na gradient.…”