An inborn error of liver fructose-1-phosphate aldolase (aldolase B) leads to a condition known as fructose intolerance. The condition is characterized by life-threatening liver damage that can occur after consuming fructose in the diet. Why is it life-threatening?
Answer
Fructokinase catalyzes the formation of fructose 1-phosphate from fructose and ATP. It is a very rapid reaction that has minimal product inhibition by fructose 1-phosphate. Normally, fructose 1-phosphate enters glycolysis after aldolase B has catalyzed its scission to yield glyceraldehyde and dihydroxyacetone phosphate; then dihydroxyacetone phosphate passes via triosephosphate isomerase to glyceraldehyde 3-phosphate and then into the final part of glycolysis, generating pyruvate. This pyruvate leads to regeneration of ATP. If aldolase B is inactive, then phosphate becomes trapped in fructose 1-phosphate which seriously compromises ATP regeneration. As a result, ATP concentrations in the liver fall dramatically, leading to a failure of the many ATP-dependent reactions including those that pump ions across the plasma membrane. This leads to irreversible damage of the hepatocytes. Even in normal individuals, the activity of aldolase B is sometimes a little lower than that of fructokinase so, in general, ingesting large doses of fructose is not advisable.
