Role of the intracellular distribution of hepatic catalase in the peroxidative oxidation of methanol.

Previous to 1950, when Bonnichsenl isolated crystalline alcohol dehydrogenase (ADH) and showed that it did not react with methanol,$ it was believed that the ADH system was responsible for the oxidation of all primary aliphatic alcohols, including methanol (FIGURE 1 ) . This observation redirected attention to the peroxidative system as a means of oxidizing methanol. As early as 1936, Keilin and Hartree3 showed that catalase catalyzed the oxidation of alcohols to their aldehydes when hydrogen peroxide was supplied in low concentrations, as might be provided in living cells through the action of flavin and other peroxide-generating enzymes. They presented arguments to support their view that catalase is not present in the tissues to protect against peroxide intoxication, as was widely contended, but rather to carry out coupled (peroxidative) oxidations. Employing techniques that permitted very rapid spectral determinations, Chance4 identified the intermediate complexes and analyzed the kinetics of the components of the reaction (FIGURE 1 ) . Ideas were exchanged for several years as to whether or not the peroxidative system participated in the in vivo oxidation of methanol and other alcohols. A direct means of examining the question was provided when Heim and coworkers5 showed that the intraperitoneal injection of 3-amino-1,2,4-triazole (AT) caused a reduction in hepatic and renal catalase activities of 90% or more. Mannering and Parkss found that the AT-induced inhibition of hepatic catalase was accompanied by a 70% reduction of the methanol-oxidizing capacity of rat liver homogenates. The addition of crystalline beef liver catalase to these homogenates restored methanol oxidation to normal. While these in vitro studies pointed to a role of catalase in methanol oxidation, they did little to establish its participation in vivo. Because of the complexity of the system, involving as it does the rate of formation of hydrogen peroxide, which in turn depends upon the concentration of substrates available to the peroxide-generating enzymes as well as the availability of hepatic catalase to the hydrogen peroxide produced by these enzymes, it seemed unlikely that in vitro studies would provide much information as to what was occurring in the intact animal. This presentation is devoted largely to a review of the evidence that shows that the intact rat oxidizes methanol largely through the peroxidative system, but that ethanol oxidation proceeds differently, probably almost entirely via the ADH system. The evidence is based on in vitro studies that employed several approaches: 1 ) 14C-methanol and 1 -Wethano1 oxidation were studied