Metabolism of Fructose (Fructolysis)

Metabolism of Fructose

(Fructolysis)

Dietary Sources of Fructose:

• The major dietary source of fructose is the disaccharide sucrose (cane sugar), and highfructose corn syrups (HFCS) used in the manufactured foods and beverages.
• Sucrose is hydrolysed in the intestine to one mol. of glucose and one mol. of fructose by the enzyme Sucrase.
• Fructose is absorbed by facilitated transport and taken by portal blood to liver, where it is mostly converted to glucose.
• It is also found in free form in honey and many fruits.

Metabolic Pathways of Fructose:

• In the body, entry of fructose into the cells is not controlled by the hormone insulin.
• This is in contrast to glucose which is regulated for its entry into majority of the tissues.
• Fructose is almost entirely metabolized in the liver in humans

Fig: Metabolism of Fructose

• Fructose may be phosphorylated to form fructose-6- P, catalysed by the enzyme hexokinase.
  • Hexokinase, which phosphorylates various monosaccharides, can also act on fructose to produce fructose 6-phosphate. But this is not the major pathway,
  • Hexokinase has low affinity (high Km) for fructose. As affinity of the enzyme hexokinase for fructose is very low,hence this is a minor pathway.

• A specific enzyme fructokinase is present in Liver .
  • Fructokinase has been identified also in kidney and intestine.
  • Fructose is mostly phosphorylated by fructokinase to fructose 1-phosphate.
  • This enzyme phosphorylates fructose only and will not phosphorylate glucose.
  • This appears to be the major pathway for phosphorylation of fructose. Its activity is not affected by insulin.
  • This explains why fructose disappears from the blood of diabetic patients at a normal rate.

• Fructose 1-phosphate is cleaved to glyceraldehyde and dihydroxyacetone phosphate (DHAP) by aldolase B.
• This is in contrast to fructose 6-phosphate which is converted to fructose 1, 6-bisphosphate and split by aldolase A (details in glycolysis).

Fate of D-glyceraldehyde:

• D-glyceraldehyde can enter glycolytic pathway when converted to either to Glyceraldehyde-3-P or to some other metabolites of glycolytic pathway.
• Glyceraldehyde is phosphorylated by the enzyme triokinase to glyceraldehyde 3- phosphate which, along with DHAP, enters glycolysis or gluconeogenesis.

Note:

• The fructose is more rapidly metabolized (via glycolysis) by the liver than glucose.
• This is due to the fact that the rate limiting reaction in glycolysis catalysed by phosphofructokinase is
  bypassed.
• Increased dietary intake of fructose significantly elevates the production of acetyl CoA and lipogenesis (fatty acid, triacylglycerol and very low density lipoprotein synthesis).
• Ingestion of large quantities of fructose or sucrose is linked with many health complications.

Fig: Overview of Fructose Metabolism

References:

Website:

• https://en.wikipedia.org/wiki/Fructolysis
• https://www.jci.org/articles/view/96702
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533803/
• https://microbenotes.com/fructose-metabolism/

Books:

• John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.
• David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
• 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.