Molecular Pharmacology, Vol 7, 169-176, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of a Reduced Nicotinamide Adenine Dinucleotide Phosphate-Linked Aldehyde Reductase from Bovine Brain by Barbiturates

¹ School of Pharmacy, University of Colorado, Boulder, Colorado 80302

The partially purified NADPH-linked aldehyde reductase (alcohol:NADP oxidoreductase, EC 1.1.1.2) from bovine brain has been further characterized, and inhibition of the enzyme by barbiturates has been investigated. In addition to substituted benzaldehydes and phenylethanols, free indoleacetaldehyde was observed to be a substrate for the enzyme. In the present studies, it was found that brain aldehyde reductase is markedly inhibited by barbital, phenobarbital, pentobarbital, and amobarbital, with K_i values ranging from 50 to 400 µM. Inhibition by these agents was reversible and of a noncompetitive type with respect to p-nitrobenzaldehyde, indoleacetaldehyde, p-hydroxyphenylglycolaldehyde, or NADPH. The enzyme was not markedly inhibited by amobarbital alcohol, a normal metabolite of amobarbital, or by barbituric acid; K_i values for these compounds were found to be 0.6 and 4 mM, respectively. Evidence is presensted suggesting that inhibition of aldehyde reductase by the barbiturates is due to the ionized form of the inhibitors. Pyrazole, a potent inhibitor of alcohol dehydrogenase, did not inhibit aldehyde reductase, and the barbiturates had no effect on alcohol dehydrogenase. The differential sensitivity of aldehyde reductase to the inhibitory effects of barbiturates and pyrazole is used to distinguish this enzyme from liver alcohol dehydrogenase.