A child born and raised in Chicago planned to spend the summer on a relative’s fruit farm and help with the harvest. The summer passed uneventfully, but several days after the harvest began the child became jaundiced and very sick. On admission to the hospital the following clinical findings were recorded: in addition to the expected hyperbilirubinemia, the patient was hypoglycemic, had a markedly elevated rise in blood fructose concentration, and was hyperlactic acidemic. Further history taking revealed that during the harvest it was customary for the family to indulge in fruit-filled meals and to snack freely on fruit while carrying out the harvest. The following conclusions were reached. The elevated blood fructose was due to which of the following?
(A) an allergic reaction to constituents in the fruit diet
(B) defective hepatic fructokinase
© defective hepatic glucokinase
(D) defective hepatic fructose-1-phosphate aldolase (aldolase B)
(E) defective hepatic fructose-1,6bisphosphate aldolase (aldolase A)
Explanation:
Patients with hereditary fructose intolerance have defective function in hepatic fructose-1-phosphate aldolase (also called aldolase B). This enzyme hydrolyzes fructose-1-phosphate to glyceraldehyde and dihydroxyacetone phosphate. The reaction is the second in the hepatic pathway of fructose metabolism, the initial one being the phosphorylation of fructose at the 1 position by fructokinase (choice B). When fructose is high in the diet (as in the consumption of large quantities of fruit) the capability to divert the fructose into the glycolytic pathway is severely impaired. Fructose becomes trapped in the liver as fructose-1-phosphate. Due to the lack of aldolase B, the capacity to phosphorylate fructose becomes limiting due to feedback inhibition of fructokinase, resulting in an elevation in serum fructose levels. Hepatic glucokinase (choice C) and aldolase A (choice E) are not involved in the metabolism of fructose. An allergic reaction (choice A) would not manifest with elevated serum fructose, hyperbilirubinemia, or hyperlacticacidemia.