{'fraction_non_alphanumeric': 0.025167125442390876, 'fraction_numerical': 0.009830908375933936, 'mean_word_length': 5.73015873015873, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Topological aspects of microsomal N-acetyltransferase, an enzyme responsible for the acetylation of cysteine S-conjugates of xenobiotics.

Acetylation of cysteine S-conjugates of xenobiotics by microsomal N-acetyltransferase is the final step of detoxicative metabolism leading to mercapturic acid biosynthesis. To elucidate the subcellular site of N-acetylation and the effective mechanism by which the final metabolites are eliminated from the organisms, topological aspects and catalytic properties of microsomal N-acetyltransferase and mercapturic acid biosynthesis in vivo were investigated. Intravenous administration of radioactive S-benzyl-L-cysteine, a model compound of cysteine S-conjugates, resulted in rapid acetylation of the conjugate in liver and kidney to a similar extent. The acetylation was followed by a rapid excretion of the metabolite, a mercapturic acid, into the urine; about 60% of the injected dose appeared in urine within 60 min of administration. Limited proteolysis of microsomal vesicles obtained from liver and kidney by chymotrypsin or trypsin inactivated the transferase by 49-62% and 62-73%, respectively. Proteolytic inactivation of the transferase was not significantly affected by the presence of 0.04% sodium deoxycholate by which the vesicles became permeable to macromolecules due to its detergent action. To determine the sidedness of the active site of N-acetyltransferase on the microsomal membranes, two S-acetyldextran polymer derivatives (Mr 500 000) of cysteine and N-acetylcysteine which represent an nonpermeant substrate and product for this enzyme, respectively, were examined for their effects on the vesicle-associated enzyme activity. Both derivatives inhibited the transferase activity in a dose-dependent fashion; maximum inhibition of the enzyme activity was 40% by the former and 60% by the latter. Sulfobromophthalein strongly inhibited the enzyme activity and this inhibition was completely reversed by adding an equimolar amount of hepatic glutathione S-transferases (ligandins). In contrast to the strong inhibition by sulfobromophthalein itself, its glutathione S-conjugate did not inhibit the enzyme activity. These results indicate that the active site and the protease-sensitive domain(s) of the microsomal N-acetyltransferase are localized on the outer surface (cytoplasmic side) of endoplasmic reticulum and that the ligandin(s) might protect membranous N-acetyltransferase from inhibition by organic anions by binding them and catalyzing the conjugation with glutathione.