AADAC deacetylates PHEN

Stable Identifier
R-HSA-5689000
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Esterases contribute to the metabolism of ~10% of therapeutic drugs. Esterases hydrolyse compounds that contain ester, amide, and thioester bonds, which result in prodrug activation or detoxification. Arylacetamide deacetylase (AADAC) is involved in the hydrolysis of flutamide, phenacetin, and rifamycins. AADAC is associated with adverse drug reactions as hydrolytic metabolites of flutamide and phenacetin are associated with hepatotoxicity and nephrotoxicity/hematotoxicity, respectively. Phenacetin (PHEN) is a mild analgesic/antipyretic drug, widely used from its introduction in 1887 until its ban in 1983. It was banned because of its adverse effects, which include increased risk of certain cancers and kidney damage. It is metabolised into paracetamol, which replaced it as an over-the-counter medication following the ban on PHEN. AADAC hydrolyses PHEN to the p-phenetidine metabolite which is a nephrotoxicant (Watanabe et al. 2010, Fukami & Yokoi 2012).

Literature References
PubMed ID Title Journal Year
20542992 Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen

Watanabe, A, Fukami, T, Takahashi, S, Kobayashi, Y, Nakagawa, N, Nakajima, M, Yokoi, T

Drug Metab. Dispos. 2010
22813719 The emerging role of human esterases

Fukami, T, Yokoi, T

Drug Metab. Pharmacokinet. 2012
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
deacetylase activity of AADAC [endoplasmic reticulum membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created