Fructose Intolerance

The metabolite fructose 1-phosphate (F 1-P) is accumulated with heredity fructose intolerance. One explanation for how this leads to disease is that it leads to trapping of a phosphate in F 1-P. This buildup of phosphate causes a decrease in the amount of free phosphates, which then results in a decreased amount of ATP. Less ATP affects the ability for some cellular processes to occur. One process that this affects is glycogenolysis. If glycogenolysis is impaired, this causes low blood glucose (hypoglycemia). This explains how heredity fructose intolerance leads to hypoglycemia. Another explanation for disease is that cellular F 1-P buildup has toxic consequences for cells. There is feedback inhibition of fructose 1-phosphate on fructokinase which leads to a decrease in the amount of fructose taken up by the liver. This reduced liver uptake causes fructose levels to increase in blood plasma (fructosemia). This explains why heredity fructose intolerance causes fructosemia.
Gluconeogenesis and glycolysis are two pathways which use the products of aldolase B.
A defect in aldolase B causes severe metabolic disease symptoms because it leads to the buildup of fructose 1-phosphate.
However, a defect in aldolase A would not cause as severe of a disease as defects in aldolase B since the products and substrates of aldolase A can be metabolized or broken down by other enzymes. Thus, a buildup of a substance would not occur and there would be no severe metabolic disease symptoms.
As previously discussed, accumulation of fructose 1-phosphate is the main cause for the severe symptoms of heredity fructose intolerance. Fructose 1-phosphate is made from the phosphorylation of fructose. The enzyme that catalyzes this phosphorylation is fructokinase. That is, fructokinase catalyzes the phosphorylation of fructose to fructose 1-phosphate. Therefore, it is logical to conclude that inhibition of liver fructokinase results in decreased levels of fructose 1-phosphate. This would seem to lead to alleviation of the severe symptoms of heredity fructose
intolerance.
There are few clinical trials which are testing liver fructokinase inhibitors because this would actually not alleviate symptoms of the disease. Rather, it would just lead to increased fructosemia (which is one of the symptoms of heredity fructose intolerance). This process was previously explained. If liver fructokinase was inhibited, this would lead to decreased levels of fructose 1-phosphate. However, this would also lead to increased levels of fructose in the blood since the fructose is not being phosphorylated. Increased fructose levels in the blood (fructosemia) is a harmful symptom. So, it would not make sense to test fructokinase inhibitors since it does not alleviate disease symptoms or treat fructose intolerance.