Enzymology and Catalytic Metabolism
Hereditary Fructose Intolerance (HFI)
Hereditary Fructose Intolerance (HFI) is a genetic condition people are born with, usually without previous family history. Individuals with this condition have difficulty metabolizing fructose and/or foods containing fructose. The individuals liver and kidneys attempt to use this sugar for energy and due to the incomplete breakdown of fructose, toxic byproducts are produced which eventually leads to serious illness.
The genetic condition causes an enzyme deficiency (fructose-1-phosphate aldolase) which in turn causes the build-up of fructose-1-phosphate . The overabundance of fructose-1-phosphate prevents glycogen breakdown and ultimately the synthesis of glucose for the body to use as energy source. With the inhibition of glucose synthesis after ingesting fructose, the individual experiences sever hypoglycemia
The symptoms of HFI area as follows:
Dislike of fruits, vegetables, candies, and baked goods.
Love of dextrose-based candies.
Preference of beverages such as milk, water, unsweetened tea, and unsweetened coffee. The feeling of nausea, queasy stomach, shaky, and/or foggy shortly after consuming fructose or sucrose. Experiencing kidney pain, hypoglycemia, and/or weakness after consuming fructose or sucrose (may be a few hours to days). The individual may eat large quantities of "safe" foods, e.g., dairy products, pasta, potato chips and rice, after ingesting fructose.
If fructose is ingested, other symptoms such as vomiting, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and eventually kidney failure will follow.
Treatment of HFI is usually difficult and requires a strict fructose free diet and the exclusion of foods containing fructose, sucrose or sorbitol. currently done through a strict fructose free diet.
Hereditary Fructose Intolerance (HFI), cont’d
A deficiency of the enzyme aldolase B cay be responsible for HFI due to the following;
Inhibition or a reduction in the breakdown of fructose 1-phosphate by aldolase B inhibits another enzyme known as fructokinase.
Free fructose may accumulate in the bloodstream, liver and kidneys.
The high fructose levels in the body affect other necessary cellular reactions and an increase in uric acid levels in the blood may be noted.
The excretion of lactic acid by the kidneys may be affected due to the kidneys attempt to excrete the increased level of uric acid which in turn may cause lactic acidosis.
Aldolase B is necessary for the production of glucose through gluconeogenesis , so a decreased level of aldolase B may cause a failure to regulate the glucose available in the body and hypoglycemia usually results.
Enzymatic Involvement in Breakdown of Fructose
The breakdown of fructose may take one of two pathways and depends on the enzymes used during the phosphorylation. The affinity of fructokinase for fructose is higher than that of hexokinase.
The liver is the predominant pathway for fructose breakdown
The liver breaks down glucose and fructose differently. There are three steps involved in the fructose-1-phosphate pathway, which is performed by the liver due to its high concentration of fructokinase relative to hexokinase:
Fructose is phosphorylated by the enzyme fructokinase to fructose-1-phosphate.
Adipose and skeletal muscle tissue also play a part in fructose breakdown but on a much smaller scale that the liver.
The breakdown of fructose in these tissues is similar to the catabolism of glucose.
Fructose is phosphorylated by the enzyme hexokinase to form fructose-6-phosphate, an intermediate of glycolysis.
Diagrams of enzymatic activity
As depicted in the diagram above, an enzyme acts a catalyst to lower the activation energy of a reaction. The enzyme’s conformation is such that the substrates easily bind to the enzyme and with the addition of sufficient energy to break bonds, the products are...
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