Fructose Metabolism Disorders


Fructose occurs in fruit, nuts, honey and some vegetables as well as a component of the disaccharide, sucrose; it is not present in human or cows' milk. Since the emergence of trade in cane‐ and beet‐sugar, fructose is now a near‐ubiquitous component of the modern diet; and consumption has continued to increase across the developed world. Industrial generation of high‐fructose products from starch in maize (corn) and other agricultural crops now enhances the availability of the fructose in commercial foods and comestibles – especially the so‐called ‘health’ or ‘energy’ drinks. High consumption of fructose and related sugars is implicated in the so‐called ‘Metabolic Syndrome’ associated with obesity, type 2 diabetes mellitus, hyperlipidaemia and premature cardiovascular disease. After incorporation into the body from the diet, entry of fructose into cells occurs rapidly but also independently of regulatory influences of insulin: as fructose esters participate critically in intermediary metabolism, inherited defects of enzymes involved in handling of exogenous fructose may have profound pathological effects. Examples are essential fructosuria, hereditary fructose intolerance and fructose‐1,6‐bisphosphatase deficiency.

Key Concepts

  • Fructose occurs as a free monosaccharide or as a component of sucrose; it is also derived from the sugar alcohol, sorbitol. Uptake of free fructose into cells via the GLUT 5 transporter occurs rapidly and is independent of insulin.
  • Rare inborn errors of fructose metabolism affect this specialised pathway for metabolic incorporation in the liver, kidney and small intestine.
  • With the appropriate level of diagnostic suspicion, facile detection of the most life threatening of these diseases is now possible by molecular analysis of genomic DNA, thus avoiding invasive biochemical investigations.
  • Global manufacture of sugar as a commodity started with the European and Arabic exploration of Africa and use of slave labour in colonial sugar plantations.
  • Changing dietary habits and global trends in food manufacture with intensified industrialisation of sugar production have exposed the toxic effects of fructose.
  • Excessive ingestion of fructose and its congeners is injurious: the sugar influences the energy status of cells and stimulates hepatic lipogenesis; these effects are exaggerated in patients with defective intermediary metabolism of fructose.

Keywords: inborn error; aldolase B; fructokinase; fructose; sucrose; metabolism; 1,6‐bisphosphatase; high‐22 fructose; industrialisation; cornstarch


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Cox, Timothy M(Dec 2015) Fructose Metabolism Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002271.pub2]