INTERACTIONS BETWEEN MONOSACCHARIDES AND DISACCHARIDES DURING UPTAKE BY THE PERFUSED LIVER OF RAT

The extractions of D‐glucose, L‐glucose, D‐fructose and D‐galactose by the isolated liver of rat perfused at constant flow were estimated by paired tracer dilution. The effects on these of 25 mM concentrations of these monosaccharides, of α‐methyl‐glucoside and of the disaccharides sucrose, maltose, and lactose were measured. Inferences were drawn from these data about the transport of monosaccharides at the sinusoidal surface of the liver cells. The hepatic clearances of the isomeric monosaccharides consistently ranked D‐glucose (at 5·5 x 10 −3 M) 〉 D‐galactose (2·5 x 10 −5 M) 〉 D‐fructose (3·2 x 10 −7 M) » L‐glucose (2 x 10 −6 M). This implies at least that there are membrane transport mechanisms with distinctly lower affinity for the other sugars than for D‐glucose. Glucose entry was stereoselective, and interactions amongst some of the sugars were demonstrated. A reproducible pattern of differential inhibition of D‐glucose entry by the competing sugars at 25 mM was found. The consistent lack of effect of sucrose excluded a mere osmotic effect. The pattern of inhibition of D‐fructose entry by the same sugars was qualitatively similar to that of D‐glucose, whereas that of D‐galactose was distinctive. The disaccharide competitors, lacking cell entry, can exert their effects only at the external surface. These markedly discriminate between D‐glucose and D‐galactose. The penetrating sugars, however, show mutual competition. The hypothesis is proposed that the external surface of the rat hepatocyte has distinct populations of hexose transport sites which discriminate between D‐glucose and D‐galactose, whereas internal sites participating in the same fluxes are unselective.