Inhibition of CO2 production from aminopyrine or methanol by cyanamide or crotonaldehyde and the role of mitochondrial aldehyde dehydrogenase in formaldehyde oxidation.
Previous results have shown that cyanamide or crotonaldehyde are effective inhibitors of the oxidation of formaldehyde by the low-Km mitochondrial aldehyde dehydrogenase, but do not affect the activity of the glutathione-dependent formaldehyde dehydrogenase. These compounds were used to evaluate the enzyme pathways responsible for the oxidation of formaldehyde generated during the metabolism of aminopyrine or methanol by isolated hepatocytes. Both cyanamide and crotonaldehyde inhibited the production of 14CO2 from 14C-labeled aminopyrine by 30-40%. These agents caused an accumulation of formaldehyde which was identical to the loss in CO2 production, indicating that the inhibition of CO2 production reflected an inhibition of formaldehyde oxidation. The oxidation of methanol was stimulated by the addition of glyoxylic acid, which increases the rate of H2O2 generation. Crotonaldehyde inhibited CO2 production from methanol, but caused a corresponding increase in formaldehyde accumulation. The partial sensitivity of CO2 production to inhibition by cyanamide or crotonaldehyde suggests that both the mitochondrial aldehyde dehydrogenase and formaldehyde dehydrogenase contribute towards the metabolism of formaldehyde which is generated from mixed-function oxidase activity or from methanol, just as both enzyme systems contribute towards the metabolism of exogenously added formaldehyde.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D005557:Formaldehyde / Q000378:metabolism*; D006038:Glyoxylates / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D003486:Cyanides; D006038:Glyoxylates; D000632:Aminopyrine; D002245:Carbon Dioxide; D005557:Formaldehyde; D003484:Cyanamide; C012796:2-butenal; D006861:Hydrogen Peroxide; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; C031150:glyoxylic acid; D000432:Methanol