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Case Study 10: A Case to Investigate Acetyl Transferase Kinetics
Dumouchel, J.L. ✉
;
Kramlinger, V.M.
Angol nyelvű Könyvfejezet (Könyvrészlet) Tudományos
Megjelent:
Jose M. Segui-Simarro. Doubled Haploid Technology. (2021) ISBN:9781071613146; 9781071613153
pp. 781-808
Azonosítók
MTMT: 32155295
DOI:
10.1007/978-1-0716-1554-6_29
WoS:
000707185700032
Scopus:
85111815684
PubMed:
34272717
Major routes of metabolism for marketed drugs are predominately driven by enzyme families such as cytochromes P450 and UDP-glucuronosyltransferases. Less studied conjugative enzymes, like N-acetyltransferases (NATs), are commonly associated with detoxification pathways. However, in the clinic, the high occurrence of NAT polymorphism that leads to slow and fast acetylator phenotypes in patient populations has been linked to toxicity for a multitude of drugs. A key example of this is the observed clinical toxicity in patients who exhibit the slow acetylator phenotype and were treated with isoniazid. Toxicity in patients has led to detailed characterization of the two NAT isoforms and their polymorphic genotypes. Investigation in recombinant enzymes, genotyped hepatocytes, and in vivo transgenic models coupled with acetylator status-driven clinical studies have helped understand the role of NATs in drug development, clinical study design and outcomes, and potential roles in human disease models. The selected case studies herein document NAT enzyme kinetics to explore substrate overlap from two human isoforms, preclinical species considerations, and clinical genotype population concerns. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
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2025-04-24 23:12
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