Sugar Transport and Fructose Metabolism in Human Intestine in Vitro.

Present knowledge regarding sugar transport by human intestine has been derived primarily by extrapolation of data from other species. Previous investigations, performed chiefly with everted sacs of hamster intestine, show that a sugar requires a specific structure before it can be transported by intestine against a concentration gradient , a process referred to as "active transport" (1, 2). Thus, in the hamster, the necessary requirements for a monosaccharide to be actively transported are a pyranose ring, a D-configuration , a hydroxyl group in the glucose configuration at carbon 2, and a methyl or substituted methyl group at carbon 5. Sugars that lack one of these features, or possess a large substituent on some part of their structure, are not actively transported. Fructose, lacking these requirements, is therefore not transported against a gradient. Nonetheless, fructose disappears from the rat intestinal lumen at a rate intermediate between that for sugars such as glucose or galactose, which are actively transported, and sugars such as mannose or pentoses, which are not (3). Since passive diffusion of a sugar through the intestinal wall is dependent upon the difference between its intracel-lular and extracellular concentration (2), the enhanced rate of fructose disappearance as compared to mannose or pentoses may be accounted This study was performed during the tenure of an Established Investigatorship of the American Heart Association. for by its partial conversion to another substance, such as lactate (4) or glucose (4-8). Conversion of fructose to glucose by the intestine was first suggested by Bollman and Mann (5) and since then has been demonstrated in the guinea pig (4, 6), hamster (7), rat (4), and dog (8). Conversion of fructose to glucose by human intestine has been assumed, but never established. Miller, Craig, Drucker, and Woodward (9), in a patient with cirrhosis of the liver given fructose orally, observed a greater glucose concentration in portal anastomotic vein blood than fe-moral arterial blood, by 5 mg per 100 ml, suggesting a conversion of fructose to glucose. Their observation that oral fructose administration produced effects other than those of parenteral fruc-tose supported the possibility of intestinal conversion , but different rates and sites of initial presentation could explain this finding. The mechanism of conversion of fructose to glucose in animals has been examined. The possible pathways are outlined in Figure 1. Fruc-tose can either be converted to glucose via initial phosphorylation to fructose-l-phosphate, cata-lyzed by fructokinase, or to …