CLINICAL CASES
221
A deficiency in aldolase B leads to the condition known as fructose intol-
erance. This inherited condition is benign as long as the patient does not con-
sume any foods with fructose or sucrose. Patients with this condition usually
develop an aversion to sweets early in life and as a result frequently are with-
out any caries. However, infants and small children if chronically exposed to
fructose-containing foods usually exhibit periods of vomiting and poor feed-
ing, as well as a failure to thrive. A defect in the aldolase B gene results in a
decrease in activity that is 15 percent or less than that of normal controls. This
results in a buildup of F1P levels in the hepatocyte. Because the maximal rate
of fructose phosphorylation by fructokinase is so high (almost an order of
magnitude greater than that of glucokinase), intracellular levels of both ATP
and inorganic phosphate (Pi) are significantly decreased. The drop in ATP con-
centration adversely affects a number of cellular events, including detoxifica-
tion of ammonia, formation of cyclic AMP (cAMP), and ribonucleic acid
(RNA) and protein synthesis. The decrease in intracellular concentrations of R
leads to a hyperuricemic condition as a result of an increase in uric acid for-
mation. AMP deaminase is inhibited by normal cellular concentrations of Pi.
When these levels drop, the inhibition is released and AMP is converted to
IMP and, ultimately, uric acid (Figure 24-2).
The toxic effects of F1P can also be exhibited in patients that do not have
a deficiency in aldolase B if they are parenterally fed with solutions contain-
ing fructose. Parenteral feeding with solutions containing fructose can result in
blood fructose concentrations that are several times higher than can be
achieved with an oral load. Since the rate of entry into the hepatocyte is
dependent on the fructose gradient across the cell, intravenous loading results
in increased entry into the liver and increased formation of F1P. Since the rate
of formation of F1P is much faster than its further metabolism, this can lead
to hyperuricemia and hyperuricosuria by the mechanisms described above.
Figure 24-2. The inhibition of AMP deaminase by inorganic phosphate (P;).
A decrease in [R] increases the activity of AMP deaminase and leads to
increased production of uric acid.
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