Enzymatic Production of Acetaldehyde from Ethanol in Rat Brain Tissue

Abstract

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.

Distribution of alcohol and sorbitol dehydrogenases

“…5) after PCR amplification. The conversion of ethanol to acetaldehyde has been described in brain, but that activity was attributable to catalase (Gill et al, 1992). Human liver class-I ADH catalyze the interconversion of alcohols and aldehydes of dopamine metabolism in vitro, with ethanol and acetaldehyde as competing substrates, whereas those of classes I1 and I11 do not (MArdh and Vallee, 1986).…”

Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

“…Many behavioral and pharmacological effects of EtOH have been hypothesized to be mediated by ACD formed in the CNS Aragon et al, 1986;Smith et al, 1984Smith et al, , 1997. Because of the very low alcohol dehydrogenase activity in the brain Gill et al, 1992), it is unlikely that ACD is formed by this pathway in brain tissue. Moreover, under physiological conditions, the ACD formed peripherally from EtOH is not likely to enter the brain because of the high aldehyde dehydrogenase activity associated with the bloodbrain barrier (Smith et al, 1997;Sippel 1974;Zimatkin, 1991).…”

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

“…Mice lacking catalase have lower levels of ethanol-induced locomotion than control animals (Aragon et al, 1992a;Aragon and Amit, 1993), and across several pharmacological manipulations there is a high positive correlation between ethanol-induced locomotor activity and brain catalase activity (Correa et al, , b, 2000(Correa et al, , 2001(Correa et al, , 2004aSanchis-Segura et al, 1999a-c;Pastor et al, 2002). Because catalase has been strongly implicated in ethanol metabolism in the brain (Aragon et al, 1991(Aragon et al, , 1992bGill et al, 1992), it is reasonable to suggest that this enzyme may regulate the motor effects of ethanol through a mechanism tied to the rate of cerebral acetaldehyde production (Aragon et al, 1989(Aragon et al, , 1991(Aragon et al, , 1992b. Previous research indicates that substantia nigra is one of the brain areas with the highest concentration of the ethanol-metabolizing enzyme catalase (McKenna et al, 1976;Brannan et al, 1981;Moreno et al, 1995;Zimatkin and Lindros, 1996), which suggests that SNr may be an important brain locus at which acetaldehyde would modulate locomotor activity.…”