In general, glucose is used directly
by tissues such as the muscles and
brain as an energy source. Excess
glucose is stored in the liver as glycogen
(a glucose polymer) but can
also be converted into fructose by the
polyol biochemical pathway (Fig. 1).
By contrast, fructose is almost exclusively
metabolized by the liver. In this
organ, ketohexokinase (KHK) — a
liver-specific fructose-metabolizing
enzyme also known as fructokinase
— traps fructose in liver cells as fructose
1-phosphate. Unlike fructose
6-phosphate (an isomer of fructose
1-phosphate that participates in the
biochemical pathway of glycolysis),
fructose 1-phosphate can bypass a
major regulatory step in glycolysis
that generates fructose 1,6-bisphosphate
through the action of the
energy-sensitive enzyme phosphofructokinase.
Thus, fructose can be converted into fat,
unfettered by the cellular controls that prevent
unrestrained lipid synthesis from glucose1,6.