Acetylation, Deacetylation and Acyltransfer

Abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. N-Substituted aromatic compounds can be metabolized in most species to N-acetylated derivatives that are themselves subject to further enzymatic transformations, including hydrolysis and NOacyltransfer. These proceses can either potentiate or ameliorate the biological responses to these Nsubstituted derivatives. Decreasing the levels of metabolites, such as arylhydroxylamines may, in some systems, reduce the probability of eliciting adverse biological effects. In others, arylhydroxamic acids produced by the acetylation of arylhydroxylamines may increase their potential for metabolic activation by NO-acyltransfer. In the rabbit, rat and perhaps other species, the acetyl CoA-dependent N-acetyltransferase is also capable of activating arylhydroxamic acids by N-O-acyltransfer. These cytosolic organotriphosphate ester-resistant enzymes can utilize arylhydroxamic acid as a donor of the acetyl moiety in the acetyl transferase reaction and apparently are capable of activating arylhydroxamic acids because of their ability to O-acetylate the arylhydroxlamine. In mice, N-acetyltransferase and NO-acetyltransferase seem not to exhibit this relationship. Enzymes from the microsomes of a number of species are also capable of activating arylhydroxamic acids. The particulate-bound enzymes are organotriphosphate ester-sensitive deacylases that are unable to form nucleic acid adducts on incubation with N-methoxy-N-acetylaminoarenes, substrates that are not capable of activation by N,O-acyltransfer. Thus, depending on the specificity of the enzymes involved, N-substituted aromatic compounds may be activated by NO-acyltransfer during both the acetylation and deacylation process. The influence of this activation in the carcinogenic process is the object of continuing investigation.

In vitro Intestinal Microflora‐Mediated Metabolism of Biliary Metabolites from 1‐Nitropyrene‐Treated Rats

“…Therefore, we determined acetyltransferase activity of IC and various organs of rats to know whether the acetylation occurred in the intestine by intestinal microflora or in the liver. Acetylation is one of the important metabolic activation pathways of aromatic amines (15). However, only limited information is available on acetylating activity of the intestinal microflora (38).…”

The Use of Metabolising Systems for In Vitro Testing of Endocrine Disruptors

“…Conjugation may not necessarily inactivate, there are many examples of Phase II (conjugate) bioactivation in mammals [294][295][296][297][298][299][300][301][302][303][304][305]. An example of a deleterious glucuronidation is glucuronidation of a carboxy group, yielding a reactive acyl glucuronide.…”

Comparison of acyltransferase‐mediated mutagenicity and nucleic acid binding of n‐acetoxy‐4‐acetylaminobiphenyl by hepatic and bladder microsomes from rats and dogs

“…The putative reactive species, N-acetoxy-4-aminobiphenyl (N-OAc-ABP) exemplified in the case of the bladder carcinogen ABP, could be formed by N-deacetylation of N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) or by O-acetylation of N-hydroxy-4-aminobiphenyl (N-OH-ABP) catalyzed by specific acyltransferases [Bartsch et al, 1973;Flammang et al, 1986;Kato and Yamazoe, 1988;Shinohara et al, 1986;Yamada et al, 19881. Evidence for the role of these acetylation and deacetylation reactions in mutagenesis and carcinogenesis comes from studies on biochemical mechanisms [Lower and Bryan, 1973;King and Glowinski, 1983;Weber and Hein 19851, DNA repair synthesis [Wang et al, 19881, and on mutagenicity [Saito et al, 1983;Weeks et al, 1978;Wirth and Thorgeirsson, 19811. Although the occurrence of these acyltransferase(s) has been known, which of these enzymes plays a determinate role in susceptibility to bladder carcinogenesis induced by arylamines and arylacetamides is currently not understood. This is partly because of the occurrence of various forms of acyl transferase(s), some which exhibit different substrate specificities, and their distribution varies between different tissues and between different experimental species [Glowinski et al, 1980;Hosokawa et al, 1990;Jarvinen et al, 1971;Mentlein and Heymann, 1984;Smith and Hanna, 1986;Wang et al, 1991 1.…”