Preliminary data have been obtained indicating that
glucose-6-phosphatase is inactivated upon preincubation with 447 and 224 mM
acetaldehyde for 30 min at room temperature, resulting in a loss of 67% and 33% of the original activity, respectively. The reaction with
acetaldehyde is rapid because 44% of the enzymic activity is lost in 5 min. Comparable quantities of
ethanol inhibit the
enzyme to the extent of 11%, indicating a very slight, statistically insignificant organic
solvent effect. Because chronic alcoholics present a clinical picture of
hypoglycemia,
hyperuricemia, reduced gluconeogenesis, and lactic acidemia, it is hypothesized that
glucose-6-phosphatase may be a focal
enzyme whose inactivation may be related to each of the disorders.
Glucose-6-phosphatase is the terminal key
enzyme in the gluconeogenesis pathway leading to increased
blood glucose. Inhibition thereof may explain both the alternate reduction of
pyruvate with concommittent increased formation of
lactic acid, and the increase in the pentose phosphate pathway leading to
hyperuricemia (as also observed in
von Gierke's disease).