Distribution and properties of aldehyde dehydrogenase in regions of rat brain.
NAD-dependent aldehyde dehydrogenases (EC 1.2.1.3) were isolated from various subcellular organelles as well as from different regions of rat brain. The mitochondrial, microsomal, and cytosolic fractions were found to contain 40%, 28%, and 12%, respectively, of the total aldehyde dehydrogenase (5.28 +/- 0.44 nmol NADH/min/g tissue) found in rat brain homogenate when assayed with 70 muM propionaldehyde at pH 7.5. The total activity increased to 17.3 +/- 2.7 nmol NADH/min/g tissue when assayed with 5 mM propionaldehyde. Under these conditions the three organelles contained 49%, 23%, and 9%, respectively, of the activity. The enzyme isolated from cytosol possessed the lowest Km. The molecular weight of the enzyme isolated from all three subcellular organelles was approximately 100,000. Four activity bands were found by electrophoresis of crude homogenates, isolated mitochondria, or microsomes on cellulose acetate strips. Cytosol possessed just two of the forms. The total activity was essentially the same in homogenates obtained from cortex, subcortex, pons-medulla, or cerebellum. Further, the enzyme had the same molecular distribution and total activity in each of these four brain regions. Disulfiram was found to be an in vivo and in vitro inhibitor of the enzymes obtained from these brain regions. Mercaptoethanol, required for the stability of the enzyme, reversed the inhibition produced by disulfiram. The effect was greater for enzyme isolated from cytosol than from mitochondria. Calculations led to the prediction that aldehydes such as acetaldehyde are oxidized in cytosol.
D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004221:Disulfiram / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008297:Male; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology; D014018:Tissue Distribution
D009243:NAD; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram