Intestinal sugar transport: Ionic activation and chemical specificity

doi:10.1016/0005-2736(69)90141-2

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 183, Issue 1, 3 June 1969, Pages 169-181

https://doi.org/10.1016/0005-2736(69)90141-2 Get rights and content

Abstract

The mode of absorption of several monosaccharides was studied in vitro with segments and everted sacs of hamster small intestine.

1.
1. Na⁺ reduced the apparent K_m of transport of the actively transported d-galactose, 3-methyl-d-glucose, α-methyl-d-glucoside, d-xylose and l-glucose. The ‘nontransported’ d-arabinose, l-arabinose, l-rhamnose, l-mannose and l-fucose showed Michaelis-Menten kinetics, but their K_m's were not significantly altered by Na⁺. The ν_max of all the sugars tested was identical and independent of Na⁺. Inhibition of entry of nontransported sugars by d-galactose and by phlorizin was demonstrated.
2.
2. By the criteria of Na⁺ dependence, inhibition by phlorizin and ouabain and inhibition by transported sugars, d-mannose and d-fructose were also shown to interact with the joint sugar carrier. The transport of d-mannose appears to be active, but rapid metabolism of the two sugars precluded a quantitative determination of transport parameters.
3.
3. The data suggest a dual specificity of a joint sugar carrier: In the absence of Na⁺ its affinity for many diverse sugars is low; the presence of Na⁺ increases the affinity for only some of these sugars. The potential for active transport depends on the extent of this activation by Na⁺ and varies with different sugars from negligible to very great.
4.
4. With low concentrations of sugar the asymmetry of transport increases towards a limiting value which depends on the ratio $K_{m(Na^{+}free)} K_{m(Na^{+})}$ . Active transport occurs with sugars where this ratio >3−5, provided their concentration is below a critical value which also parallels the K_m ratio.

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Cited by (37)

Na<sup>+</sup>-dependent fructose transport via rNaGLT1 in rat kidney
2003, FEBS Letters
We found a system of Na⁺-dependent uptake of fructose by rat renal brush-border membrane vesicles. It consisted of two saturable components, and was thought to involve at least two transporters. rNaGLT1, a novel glucose transporter in rat kidney, showed fructose uptake as well as α-methyl-D-glucopyranoside uptake by transfected HEK293 cells. The features of the lower affinity type of fructose transporter in the brush-border membranes, such as affinity and substrate recognition, were very comparable with those of rNaGLT1-transfected HEK293 cells. These results indicated that rNaGLT1 is a primary fructose transporter in rat renal brush-border membranes.
Paracellular intestinal transport of six-carbon sugars is negligible in the rat
1995, Gastroenterology
$Background & Aims$ : Active d-glucose absorption has been theorized to increase convective flow and enhance tight junction permeability such that paracellular transport becomes the major mechanism of d-glucose absorption. This concept was tested in rats by measuring the absorption of four gavaged, nonmetabolizable six-carbon sugars (l-glucose, l-galactose, l-mannose, and d-mannitol) thought to be absorbed solely by the paracellular route. $Methods$ : Uptake of gavaged probes was measured by recovery in 24-hour urine specimen collections. $Results$ : l-glucose (71.2% ± 2.4%) absorption exceeded that of the other probes (1.4%–9%). Coadministration of 3.0 mol/L d-glucose, 0.22 mol/L d-glucose, or chow significantly reduced the absorption of l-glucose to 38.1% ± 7.2%, 61% ± 3.3%, and 53.6% ± 3.5%, respectively, but did not influence the absorption of the other six-carbon probes. $Conclusions$ : (1) l-glucose seems to have a weak affinity for a d-glucose carrier and is not a marker of paracellular transport, and (2) paracellular transport accounts for a minimal fraction of d-glucose uptake; this fraction is not enhanced by ingestion of d-glucose or chow.
Sugar absorption by the biliary ductular epithelium of the rat: Evidence for two transport systems
1992, Gastroenterology
Sugar absorption by the biliary ductular epithelium under steady-state conditions was examined using isolated perfused rat liver. The test sugar and mannitol (as a putative marker of paracellular entry) were added to the glucose-free recirculating perfusate each at a concentration of 5 mmol/L, and apparent active biliary ductular absorption equated with the change in concentration of the test sugar relative to that of mannitol. A metabolizable hexose (d-glucose), pentose (d-xylose), and three nonmetabolizable hexoses (α-methyl-glucoside, 3-o-Methyl-glucose, and l-glucose) were used. All five monosaccharides were well absorbed at constant rates for 2 hours with apparent rates of absorption (μmol · kg body weight⁻¹ · min⁻¹, mean ± SE) of d-glucose, 0.24 ± 0.01; l-glucose, 0.20 ± 0.02; 3-o-Methyl-glucose, 0.19 ± 0.02; α-methyl-glucoside, 0.16 ± 0.03; and d-xylose, 0.10 ± 0.04. The addition of phloridzin to the perfusate inhibited d-glucose absorption in part but did not inhibit l-glucose absorption. When perfusate Na⁺ was replaced by N-Methylglucamine, the bile-plasma ratio of mannitol remained unchanged, as did the apparent absorption rate of d-glucose and 3-o-Methyl-glucose. In contrast, absorption of l-glucose and α-methyl-d-glucoside gradually ceased. The addition of 15 mmol/L glucose to the perfusate caused decreased bile flow and increased taurocholate concentration in bile, suggesting that glucose absorption by the biliary ductules induced water reabsorption. It is concluded that sugars are absorbed by the biliary ductular system by Na⁺-dependent and Na⁺-independent transport systems, the substrate affinities of which differ from those reported for apical membrane hexose transport systems in renal tubular and intestinal epithelia. Ductular absorption of solutes such as glucose that enter bile passively may have biological use, because ductular absorption decreases the concentration of substrates for bacterial growth in gallbladder bile. On the other hand, ductular absorption of solutes induces reabsorption of biliary water, resulting in decreased bile flow; this might contribute to cholestasis during prolonged hyperalimentation with solutions containing glucose.
Fructose transport by rat intestinal brush border membrane vesicles. Effect of high fructose diet followed by return to standard diet
1991, Comparative Biochemistry and Physiology -- Part A: Physiology
- 1.
  1. d-Fructose uptake in isolated rat intestinal brush border membrane comprised a simple diffusional component and a saturable, carrier-mediated, component. The latter did not follow typical Michaelis-Menten kinetics and appeared as a low affinity, high capacity process (K_t = 110 mM, J_max = 160.5 nmol/min-mg protein).
- 2.
  2. Carrier-mediated D-fructose uptake was highly specific, Na independent and unaffected by phloridzin and metabolic inhibitors.
- 3.
  3. Fructose feeding for 3 days resulted in an activation of d-fructose uptake after a latent period superior to 3 days. The increase was of relatively short duration since it was not further observed 6 days after the return to the standard diet.
- 4.
  4. The activation in d-fructose uptake was due to a slight decrease in K_t and a marked increase in J_max (from 160.5 to 306 nmol/min · mg protein), suggesting a rise in the number of transporters.
Alternate models for shared carriers or a single maturing carrier in hexose uptake into rabbit jejunum in vitro
1987, BBA - Biomembranes
The uptake (tissue accumulation) of three hexoses into rabbit jejuum was measured in a flux chamber in conditions of effective stirring. Glucose uptake was inhibited by galactose or 3-O-methylglucose: 1–40 mM galactose caused a progressive decline in glucose uptake; 1–5 mM 3-O-methylglucose inhibited glucose uptake but higher concentrations of 3-O-methylglucose had no further effect. When 1–40 mM 3-O-methylglucose was added to glucose plus galactose there was a further decrease in the uptake of glucose; adding 1–40 mM galactose to glucose plus 3-O-methylglucose also produced a decrease in glucose uptake. Both glucose and 3-O-methylglucose inhibited uptake of galactose but the pattern of inhibition varied between the two sugars. The uptake of 3-O-methylglucose was also inhibited by glucose and by galactose, but the uptake of 3-O-methylglucose in the presence of either galactose or glucose was no further reduced by adding the third hexose. Graphical analysis and analysis by non-linear regression both showed that neither the single Michaelis-Menten function, nor the single Michaelis-Menten-plus-competitive-inhibition function was appropriate for any of these data. The results are consistent with the hypothesis that either there are multiple (at least three) intestinal carriers for hexoses; alternatively that there is a single carrier whose transport properties for the three hexoses change differentially during cell maturation and migration up the villus.
Photoaffinity labeling and identification of (a component of) the small-intestinal Na<sup>+</sup>, D-glucose transporter using 4-azidophlorizin
1981, FEBS Letters

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Intestinal sugar transport: Ionic activation and chemical specificity

Abstract

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

Arch. Biochem. Biophys.

Life Sci.

Pharmacol. Rev.

Nature