Enzymatic production of acetaldehyde from ethanol in rat brain tissue.
The capacity for the brain to produce acetaldehyde (AcHO) from ethanol was determined in rat brain homogenates. Rat brains were perfused with saline-heparin solution and homogenized in a phosphate buffer. Varying amounts of tissue were incubated with ethanol (0-100 mM) for periods of up to 60 min. The reaction was stopped by the addition of desferrioxamine and ice-cold perchloric acid. Supernatants were treated with dinitrophenylhydrazine reagent, extracted with isooctane in the presence of an internal standard, and the derivatives were separated by HPLC. The addition of 4-methyl pyrazole (an alcohol dehydrogenase inhibitor) or metyrapone (a cytochrome P450 inhibitor) had no effect on the amount of recovered AcHO. On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3-amino-1,2,4-triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide-generating system enhanced the production of AcHO. Overall, these results suggest that AcHO may be produced in the brain during alcohol intoxication, through the action of the enzyme catalase.
Gill
K
K
Pharmacology Department, University of Colorado Health Sciences Center, Denver.
Menez
J F
JF
Lucas
D
D
Deitrich
R A
RA
D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000502:physiology; D000435:Alcoholic Intoxication / Q000201:enzymology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002374:Catalase / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D000431:Ethanol / Q000493:pharmacokinetics*; D051381:Rats
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D002374:Catalase; D000079:Acetaldehyde