4. Catabolism of sugars other than glucose

4.2 Degradation of fructose and sucrose

• The fructolysis pathway
• Fructose intolerance

Sucrose is produced from sugar cane and sugar beet, which contain it in high concentrations (15–20%). In a typical Western diet, it may amount to as much as 20% of the total carbohydrate intake. Sucrose consists of glucose and fructose joined by a ?-glycosidic bond between the carbon 1 of glucose and carbon 2 of fructose.

The hydrolytic cleavage of sucrose, like that of of maltose, occurs at the surface of the intestinal epithelial cells. The enzyme responsible is ?-fructosidase, also named sucrase. Both sugars are then taken up by specific transport: Glucose by the SGLT1 transporter, and fructose by the GLUT5 transporter, which is named after glucose but actually transports fructose more effectively than glucose.

4.2.1 The fructolysis pathway

Fructose degradation, also called fructolysis, runs mostly in the liver. In the first step, fructose is phosphorylated by fructokinase (1), which uses ATP as a cosubstrate. This yields fructose-1-phosphate. The latter is then cleaved by aldolase B (2). The products of this reaction are dihydroxyacetone phosphate, which is already a metabolite in glycolysis, and glyceraldehyde, which can enter glycolysis after phosphorylation by glyceraldehyde kinase (4).

Glyceraldehyde can alternately be utilized by conversion to glycerol and then to glycerol-1-phosphate. The latter is a substrate in the synthesis of triacylglycerol, that is, fat. Fructose and sucrose appear to promote obesity more strongly than equivalent amounts of starch or glucose, and it has been suggested that its utilization via glycerol-1-phosphate, with subsequent triacylglycerol synthesis, may be among the reasons.

4.2.2 Fructose intolerance

Fructose intolerance is a hereditary disease caused by a homozygous defect in the aldolase B gene. In this condition, fructose is still phosphorylated by fructokinase. The resulting fructose-1-phosphate, however, cannot be processed further, and therefore the phosphate tied up in it cannot be reclaimed. Since phosphate is required for the regeneration of ATP from ADP, this means that ATP will be lacking, too, which will sooner or later damage or even destroy the cell. Accordingly, the disease is characterized by potentially severe liver failure.

Fructose, alone or in combination with glucose, has been used in the past in the intravenous nutrition of intensive care patients; the perceived advantage of this treatment was the insulin-independent utilization of fructose. However, large intravenous dosages of fructose can significantly deplete liver ATP [1]Author: Bode, J C;Zelder, O;Rumpelt, H J;Wittkamp, U
Title: Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat
Journal: Eur J Clin Invest
Pages: 436-41
Volume: 3
Year: 1973
ISBN: 0014-2972; apparently, under heavy load, aldolase B may be unable to keep up with fructose kinase. Fructose is no longer a major component of intravenous nutrition schemes.

A defect in the gene encoding fructokinase leads to a condition named fructosemia or fructosuria. As these names suggest, fructose levels are increased both in the blood*Haima is the Greek word for blood; hematology is the medical discipline that deals with diseases of the blood. and the urine. Since fructose is not phosphorylated, no phosphate depletion occurs, and the liver cells do not incur any damage. The disease is therefore quite benign.

Lecture notes on human metabolism