Glucose, fructose, and sucrose are natural nutritive sweeteners; sucrose is composed of one molecule of glucose linked to one molecule of fructose; high fructose corn syrup is a mixture of free glucose and fructose; glucose and fructose are ingested in roughly isomolar when consuming nutritive sweeteners.
Glucose can be metabolized by all cells of the organism, because the enzymes hexokinases required for synthesis of glucose-6-phosphate and glycolytic enzymes are ubiquitously distributed.
Fructose is not readily phosphorylated by hexokinases and is metabolized almost exclusively in the gut, liver, and kidney that express the enzymes fructokinase for synthesis of fructose-1-phosphate and aldolase B for degradation of fructose-1-phosphate to trioses.
After ingestion of a pure glucose meal, only 15 % is taken up by the liver to replenish hepatic glycogen, and the remaining 85 % is metabolized in extrahepatic cells; postprandial glucose metabolism is regulated by insulin.
After ingestion of a pure fructose load, the major portion (close to 95 %) is taken up by the gut and the liver; about 50 % is subsequently released in the blood as glucose and about 25 % as lactate, which can be used by extrahepatic cells as energy substrate; up to 20 % can be stored as hepatic glycogen; a minor portion can be converted into fat to be stored in liver fat stores or be secreted as VLDL–triglycerides. Arterial blood fructose concentration increases transiently up to 500–600 μmol/L. Such concentrations are thought to be too low to trigger a significant renal utilization.
With intravenous fructose infusion, high arterial fructose concentration can be attained; this is associated with a significant renal fructose uptake; in renal cells, fructose is converted mainly into lactate in normally fed subjects but can be converted into glucose in 60-h fasted subjects.
Fructose metabolism is associated with a low energy efficiency compared to glucose.
Under special conditions, such as massive carbohydrate overfeeding, both glucose and fructose can be converted into fat and increase body fat stores. This process has a high energy cost and is associated with substantial amounts of energy dissipated as heat. At lower levels of intake, fructose stimulates hepatic de novo lipogenesis to a larger extent than glucose, but this represents a minor pathway for total fructose disposal.
Genetic mutations associated with loss of function of aldolase B are responsible for hereditary fructose intolerance. In this rare condition, ingestion of fructose-containing foods causes an accumulation of fructose-1-phosphate together with a decreased ATP concentration in fructokinase-expressing cells. In the liver, it acutely inhibits gluconeogenesis and causes hypoglycemia upon exposure to fructose; in the kidney, it causes renal proximal acidosis and acute dysfunctions of the proximal renal tubule.