Initial steps in the metabolism of dietary monosaccharides

Dietary carbohydrates are converted to three principal dietary monosaccharides (glucose, fructose, and galactose) during the digestive process, via the activity of enzymes that catalyze the hydrolysis of glycosidic linkages. This process takes place in the duodenum of the small intestine. Monosaccharides are then absorbed across the intestinal mucosa through transport proteins and taken up into the bloodstream, where they travel to the liver via the hepatic portal vein and are transported into hepatocytes. Here, fructose and galactose are immediately phosphorylated through the activity of the liver kinases (fructokinase and galactokinase) and are subsequently converted to glucose via the gluconeogenic metabolic pathway. Phosphorylated fructose can also feed directly into the glycolytic pathway. In contrast to fructose and galactose, hepatic glucose remains unphosphorylated for a longer period of time, despite the presence in hepatocytes of glucokinase and hexokinase. Unphosphorylated glucose is able to diffuse back out of hepatocytes and circulate throughout the body, where it serves as the principal substrate for cellular respiration in all tissues and cell types.

The following graphs depict time-course measurements of plasma fructose, glucose, and insulin after ingestion of 75 g of glucose or 75 g of fructose by human subjects.

Figure 1. Change in plasma glucose and fructose (top) and plasma insulin (bottom) in healthy human subjects following ingestion of 75 g of glucose or 75 g of fructose. The dashed line (top) depicts change in plasma glucose after ingestion of 75 g of glucose; the solid line depicts change in plasma glucose after ingestion of 75 g of fructose; the dotted line depicts change in plasma fructose after injection of 75 g of fructose.

Figure adapted from: Tappy, L., Randin, J. P., Felber, J. P., Chiolero, R., Simonson, D. C., Jequier, E., & DeFronzo, R. A. (1986). Comparison of thermogenic effect of fructose and glucose in normal humans. Am J Physiol, 250(6 Pt 1), E718-724.