N-Acetyl-transferase and Serotonin Metabolism in Man and, other Species, I

Abstract

Purified enzyme preparations from liver of human, monkey (Macaca mulatta) and rat (Mus rattus, Wistar II) acetylate isoniazid and serotonin with acetyl-coenzyme A or A^S-diacetylcysteamine as acetyl donor. The acetylation reactions of both isoniazid and serotonin are probably catalyzed by the same 7V-acetyltransferase protein. Serotonin is a physiological substrate for 7V-acetyltransferase.The role of N-acetyltransferase in the metabolism of serotonin with regard to its relationship with 5hydroxytryptophan decarboxylase and monoamine oxidase seems to be similar for all three species. This is the basis for applying experimental data performed in M. mulatta and rat to man. Various psychotropic drugs are strong inhibitors of the Nacetyltransferase. Zusammenfassung: Untersuchung einer N-Acetyl-Transferase im Serotoninstoffwechsel beim Mensehen und anderen Species, Von angereichertenLeberpräparatep verschiedener Species -Mensch, Macaca mulatta (Rhesusaffe) und Mus rattus (Wistarratte II) -wird Isonicotinsäurehydrazid und ebenfalls Serotonin (5-Hydroxy-tryptamin) in Gegenwart von Acetyl-coenzym A und N.S-Oiacetyl-cysteamin acetyliert. Die Acetylierung beider Substanzen erfolgt wahrscheinlich durch dieselbe 7V-Acetyl-Transferase. Es muß angenommen werden, daß Serotonin ein physiologisches Substrat dieses Enzyms ist. Verschiedene Charakteristika der Af-Acetyl-Transferase, der 5-Hydroxy-tryptophan-Decarboxylase und der Monoamin-Oxydase wurden bei den drei genannten Species verglichen. Einige Psychopharmaka und andere Monoamin-Oxydase-Hemmer sind starke Inhibitoren der beschriebenen 7V-Acetyl-Transferase.Abbreviations: PPO = 2,5-diphenyloxazol; POPOP = l,4-bis-[4-methyl-5-phenyl-2-oxazolyl]benzene.Brought to you by | Purdue University Libraries Authenticated Download Date | 6/25/15 9:36 PM * We are grateful to the Heinrich-Pette-Institut (Hamburg) for supplying us with livers of M. mulatta.

Acetylation of S-substituted cysteines by a rat liver and kidney microsomal N-acetyltransferase

“…The microsomal location of the S-substituted cysteine N-acetyltransferase makes it clear that it differs from the soluble N-acetyltransferases which catalyse acetylation of many endogenous and foreign amines (Weber & Cohen, 1967;Schloot et al, 1969;Hearse & Weber, 1973), and distinguish it also from the soluble glucosamine 6-phosphate N-acetyltransferase (Davidson et al, 1957). The acetylation of putrescine by a liver microsomal preparation has been reported (Seiler & Al-Therib, 1974).…”