Fructose Metabolism Overview

Fructose enters cells and is phosphorylated to fructose-1-phosphate by fructokinase (also called ketohexokinase). This reaction primarily occurs in the liver. Fructose-1-phosphate is then cleaved by aldolase B into dihydroxyacetone phosphate (DHAP) and glyceraldehyde, which enter glycolysis or gluconeogenesis pathways.

Alternatively, fructose can be phosphorylated to fructose-6-phosphate by hexokinase in extrahepatic tissues such as muscle and adipose tissue, but this reaction is less efficient due to hexokinase’s lower affinity for fructose.

Tissue-Specific Fructose Metabolism

1. Liver

• The liver is the primary site for fructose metabolism.

• Fructokinase in the liver efficiently phosphorylates fructose to fructose-1-phosphate.

• This pathway bypasses the key regulatory step of glycolysis (phosphofructokinase), allowing rapid fructose utilization.

• The liver then converts intermediates into glucose, glycogen, or lipids.

2. Muscle and Adipose Tissue

• These tissues have low fructokinase activity.

• Fructose can be phosphorylated by hexokinase to fructose-6-phosphate but with lower efficiency.

• Fructose metabolism in these tissues is limited compared to the liver.

3. Intestine

• The intestine absorbs fructose but does not significantly metabolize it via fructokinase.

• Fructose is transported to the liver for metabolism.

Why Liver Is the Correct Answer

• Fructokinase is highly expressed in the liver.

• The liver efficiently converts fructose to fructose-1-phosphate, a precursor that eventually forms fructose-6-phosphate through downstream metabolism.

• Muscle and adipose tissues rely mainly on hexokinase, which has a low affinity for fructose, making their conversion inefficient.

• Intestine primarily functions in absorption rather than metabolism of fructose.

Summary Table

Conclusion

The liver is the tissue where fructokinase efficiently converts fructose to fructose-6-phosphate (via fructose-1-phosphate intermediates). This efficient metabolism supports the liver’s central role in fructose utilization and energy homeostasis.

Correct answer: (1) Liver