Metabolism of dietary fructose

Fructose is mainly metabolized in the liver, renal cortex, and small intestinal mucosa in a pathway composed of fructokinase, aldolase B, and triokinase. Aldolase B also intervenes in the glycolytic-gluconeogenic pathway.

Fructose enters the cell via the fructose transporter GLUT5 and GLUT2. Liver enzyme fructokinase phosphorylates fructose to fructose-1-phosphate. This is cleaved by fructose-1-phosphate aldolase (aldolase B) to form dihydroxyacetone phosphate and glyceraldehyde. Glyceraldehyde is then phosphorylated by triokinase to glyceraldehyde-3-phosphate. Thus, the intermediary metabolites of fructose enter glycolysis and the tricarboxylic acid (Krebs) cycle as triose phosphates.

• Hereditary fructose intolerance is caused by aldolase B deficiency; this results in accumulation of fructose-1-phosphate and fructose-1,6-bisphosphate, which impairs the glycolytic and gluconeogenic pathway.
• Benign fructosuria is an asymptomatic condition caused by fructokinase deficiency. Benign fructosuria is characterized by elevation of plasma fructose concentration and urine excretion of fructose following ingestion of dietary fructose, sucrose, or sorbitol.
• Fructose-1,6-bisphosphatase deficiency is a disorder of gluconeogenesis characterized by episodic hypoglycemia, severe lactic acidosis, hyperuricemia, hypertriglyceridemia, and failure to thrive (similar to glycogen storage disease type 1). However, glycogenolysis is intact and liver size is only slightly increased.