SOME ENZYMIC ASPECTS OF THE PRODUCTION OF OXIDIZED OR REDUCED METABOLITES OF CATECHOLAMINES AND 5‐HYDROXYTRYPTAMINE BY BRAIN TISSUES

Abstract The Michaelis constants of purified aldehyde dehydrogenase (aldehyde: NAD oxidoreductase, EC 1.2.1.3) and aldehyde reductases (alcohol: NADP oxidoreductase, EC 1.1.1.2) from pig brain have been obtained for a number of biologically important aldehydes. The aldehydes include 3,4‐dihydroxyphenylacetaldehyde, D‐3,4‐dihydroxyphenylglycolaldehyde, and 5‐hydroxyindoleacetaldehyde. The relative activities of the aldehyde‐catabolizing enzymes in the soluble fractions of the cerebral cortex and caudate nucleus of pig brain have also been obtained. The values are used to show that the metabolic fates of the various aldehydes—and hence of the parent amines—may be explained in terms of the simple kinetics of these enzymes. It is also shown that the metabolic fates of the aldehydes may be influenced by their rates of synthesis. As the rate of aldehyde production increases the proportion of aldehyde reduced may be expected to increase at the expense of the proportion of aldehyde oxidized. It is further concluded from the kinetic constants that selective inhibition of aldehyde dehydrogenase may greatly affect the catabolism of dopamine and 5‐hydroxytryptamine by altering the relevant aldehyde concentrations, while the catabolism of norepinephrine is little affected under these circumstances. Conversely, it is concluded that selective inhibition of the aldehyde reductases should scarcely affect the catabolism of dopamine and 5‐hydroxytryptamine, but that the catabolism of norepinephrine should be markedly affected. The results also indicate that the concentrations of the various deaminated metabolites of the biogenic amines could be selectively controlled by modulation of the activity of the enzymes of aldehyde catabolism in brain.