A hypothesis linking hypoglycemia, hyperuricemia, lactic acidemia, and reduced gluconeogenesis in alcoholics to inactivation of glucose-6-phosphatase activity by acetaldehyde

Alcohol
A S Brecher, M D Lehti

Abstract

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).

References

Jan 1, 1991·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·S WorrallP A Wilce
Feb 1, 1990·Pharmacology, Biochemistry, and Behavior·K HatakeI Ijiri
Dec 9, 1989·Lancet·G M AddisonJ V Leonard
Aug 3, 1989·The New England Journal of Medicine·H Y LinI H Fox
Oct 1, 1989·Current Opinion in Rheumatology·C A Agudelo
Nov 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R C Lin, L Lumeng
Mar 31, 1986·FEBS Letters·R J Mayer, F Doherty
Aug 1, 1986·The American Journal of Physiology·R J Beynon, J S Bond
Feb 1, 1988·The Journal of Clinical Investigation·R C LinL Lumeng
Jul 29, 1988·Biochemical and Biophysical Research Communications·U J BehrensC S Lieber
Nov 1, 1984·Proceedings of the Society for Experimental Biology and Medicine·L B Nguyen, C M Peterson
Jan 1, 1983·Archives of Biochemistry and Biophysics·T M DonohueM F Sorrell
Feb 1, 1981·The Journal of Clinical Investigation·V J StevensC M Peterson
Mar 1, 1996·Alcohol·A S BrecherJ Knight
Aug 1, 1948·Journal of the American Chemical Society·H FRAENKEL-CONRAT, H S OLCOTT

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Citations

Mar 13, 2012·Journal of Cardiovascular Pharmacology·Arthur S Brecher, Anum H Riaz
Mar 13, 2013·The Journal of Clinical Investigation·Lihong JiangGraeme F Mason
Jan 15, 2014·American Journal of Epidemiology·Stephen P JuraschekElizabeth Selvin
Sep 17, 2013·Journal of Neurochemistry·Jie WangGraeme F Mason

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