Fructose Metabolism

• Fructose is an abundant sugar in the human diet.
• This dietary monosaccharide is present naturally in fruits and vegetables, either as free fructose or as part of the disaccharide sucrose, and as its polymer inulin.
• Sucrose (table sugar) is a disaccharide which when hydrolyzed yields fructose and glucose.
• The metabolism of fructose from dietary sources is referred to as fructolysis.

Location of Fructose Metabolism

• Fructose metabolism takes place primarily in the cytoplasm of cells of the liver.
• Substrate: Fructose (which is derived from breakdown of sucrose in small intestine).

The Pathway of Fructose Metabolism

There are two pathways for the metabolism of fructose; one occurs in muscle and adipose tissue, the other in liver.

1. In muscle and adipose tissue, fructose can be phosphorylated by hexokinase (which is capable of phosphorylating both glucose and fructose) to form fructose 6-phosphate which then enters glycolysis.
2. In liver, the cells contain mainly glucokinase instead of hexokinase and this enzyme phosphorylates only glucose. Thus in liver, fructose is metabolized instead by the fructose 1-phosphate pathway:
   • Fructose is converted to fructose 1-phosphate by fructokinase with the use of an ATP.
   • Fructose 1-phosphate is then split into glyceraldehyde and dihydroxyacetone phosphate by fructose 1-phosphate aldolase.
   • The dihydroxyacetone feeds into glycolysis at the triose phosphate isomerase step.
   • The glyceraldehyde is phosphorylated by triose kinase to glyceraldehyde 3-phosphate using another ATP and so also enters glycolysis.

Results: Generates 2 intermediate molecules of glycolysis for each molecule of fructose.

Energy Requirement: Requires 2 ATP.

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Significance

• Allows fructose to be converted into intermediate molecules in the glycolysis pathway.
• Since this pathway bypasses the rate-limiting step in glycolysis, fructose is metabolized to pyruvate more rapidly than glucose.

References

1. David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
2. Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.
3. John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.