Figure 1.

The hepatic metabolism of fructose and glucose

The uptake of fructose in the intestinal epithelium and its transport into the portal venous circulation take place independently of insulin by means of the highly specific fructose transporter GLUT5. In the liver, hepatocellular uptake of fructose and glucose is facilitated by the insulin-independet transporter GLUT2. Degradation of glucose to fructose-1,6-phosphate occurs with the aid of the key enzyme of glycolisis phosphofructokinase-1, whereas degradation of fructose circumvents this regulatory mechanism. The metabolism of both monosaccharides leads to the generation of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which are degraded to pyruvate in glycolysis. As there is no feedback mechanism regulating fructose metabolism, acetyl-CoA substrate accumulation ensues, exceeding the capacity of the citrate cycle. Excess citrate serves as a substrate for de novo lipogenesis. Fructose is converted to fructose-1-phosphate with the consumption of ATP. The resulting ADP is degraded to uric acid, which inhibits endothelial NO synthase, thereby contributing to arterial hypertension. ADP, adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; GLUT, glucose transporter; P, phosphate; VLDL, very low density lipoproteins. Adapted from (e25).