The effect of hydralazine and other drugs on the kinetics of procainamide acetylation by rat liver and kidney N-acetyltransferase.
The objectives of this study were to investigate 1) the tissue distribution of procainamide acetylase activity in the rat and 2) the kinetics of procainamide acetylation by rat liver and kidney N-acetyltransferase and 3) to determine the effect of drugs thought to be similarly acetylated on procainamide acetylation. The cytosol fraction (100,000 X g) of tissue homogenates served as the source of N-acetyltransferase. Of the tissues studied the liver possessed the greatest acetylase activity followed by the kidney, lung, intestine and spleen. The apparent procainamide Michalis constant (Km) for liver and kidney was 2.03 X 10(-4) and 2.09 X 10(-4) M in the presence of 4.2 X 10(-4) M acetyl CoA. The liver Km for procainamide with "infinite" acetylCoA concentration was 4.36 X 10(-3) M. The liver Km for acetyl CoA in the presence of "infinite" PA concentration was 2.44 X 10(-3) M. Hydralazine, para-aminobenzoic acid, isoniazid, and sulfapyridine competitively inhibited procainamide acetylation by liver and kidney N-acetyltransferase.
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011342:Procainamide / Q000378:metabolism*; D051381:Rats
D006830:Hydralazine; D000123:Acetyltransferases; D011342:Procainamide