A HYPOTHESIS LINKING HYPOGLYCEMIA, HYPERURICEMIA, LACTIC ACIDEMIA, AND REDUCED GLUCONEOGENESIS IN ALCOHOLICS TO INACTIVATION OF GLUCOSE-6-PHOSPHATASE ACTIVITY BY ACETALDEHYDE

Preliminary data have been obtained indicating that glucose-6-phosphat ase 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 i s rapid because 44% of the ezymic activity is lost in 5 min. Comparabl e quantities of ethanol inhibit the enzyme to the extent of 11%, indic ating a very slight, statistically insignificant organic solvent effec t. Because chronic alcoholics present a clinical picture of hypoglycem ia, 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-phosph atase is the terminal key enzyme in the gluconeogenesis pathway leadin g 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 lea ding to hyperuricemia (as also observed in von Gierke's disease). Copy right (C) 1996 Elsevier Science Inc.