CASE FILES: BIOCHEMISTRY
capacity. Thus, in most individuals, ingestion of fructose in amounts greater
than 0.5 to 1.0 g/kg body weight can result in malabsorption. Fructose enters
the bloodstream, along with glucose and galactose, via the GLUT 2 trans-
porter. Fructose is taken up by the liver by the same GLUT 2 transporter,
along with glucose and galactose. There is a large gradient between the extra-
cellular and intracellular concentrations of fructose in the liver cells, indicat-
ing that the rate for fructose uptake by the hepatocyte is low.
In the liver, kidney, and intestine, fructose can be converted to glycolytic/
gluconeogenic intermediates by the actions of three enzymes—fructokinase,
aldolase B, and triokinase (also called triose kinase)—as shown in Figure 24-1.
In these tissues, fructose is rapidly phosphorylated to fructose 1-phosphate
(F1P) by fructokinase at the expense of a molecule of adenosine triphosphate
(ATP). This has the effect of trapping fructose inside the cell. A deficiency in
this enzyme leads to the rare but benign condition known as
In other tissues such as muscle, adipose, and red blood cells, hexokinase
can phosphorylate fructose to the glycolytic intermediate fructose 6-phosphate
Fructose 1-phosphate is further metabolized to dihydroxyacetone phos-
phate (DHAP) and glyceraldehyde by the hepatic isoform of the enzyme
aldolase, which catalyzes a reversible aldol condensation reaction. Aldolase is
present in three different isoforms. Aldolase A is present in greatest concen-
trations in the skeletal muscle, whereas the B isoform predominates in the
liver, kidney, and intestine. Aldolase C is the brain isoform. Aldolase B has
similar activity for either fructose 1,6-bisphosphate (F16BP) or F1P; however,
the A or C isoforms are only slightly active when F1P is the substrate.
Glyceraldehyde may be converted to the glycolytic intermediate, glyceralde-
hyde 3-phosphate (GAP), by the action of the enzyme triokinase. This enzyme
phosphorylates glyceraldehyde at the expense of another molecule of ATP. The
GAP can then enter into the glycolytic pathway and be further converted to pyru-
vate, or recombine with DHAP to form F16BP by the action of aldolase.
Figure 24-1. The metabolic pathway for the entrance of fructose into the gly-
colytic pathway. Fructokinase rapidly converts fructose to fructose 1-phosphate,
which in the liver is cleaved by aldolase B to dihydroxyacetone phosphate
(DHAP) and glyceraldehyde.