CES1,CES2 hydrolyze ASA- to ST

Stable Identifier
Reaction [transition]
Homo sapiens
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CES1 and CES2 hydrolyze acetylsalicylate (ASA-) in hepatic cells. Although ASA- is also hydrolyzed to salicylate (ST) without enzymatic assistance, this process is rather slow (Rowland et al, 1972; Dressman et al, 2012). In gastrointestinal mucosa cells the predominant esterase is carboxylesterase 2 (CES2) (Imai et al, 2006), and in liver it has significant activity. In liver the main aspirin esterase is CES1, with minor presence of CES2 (Inoue et al, 1980; Imai et al, 2006; Schwer et al, 1997). Both enzymes hydrolyze ASA-, producing acetate and ST (Tang et al, 2006; Imai, 2006; Lian et al, 2017).
Literature References
PubMed ID Title Journal Year
7206363 Comparative study of human intestinal and hepatic esterases as related to enzymatic properties and hydrolizing activity for ester-type drugs

Tsuboi, M, Inoue, M, Morikawa, M, Sugiura, M, Ito, Y

Jpn J Pharmacol 1980
16858120 Human carboxylesterase isozymes: catalytic properties and rational drug design

Imai, T

Drug Metab Pharmacokinet 2006
22674043 Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid

Polli, JE, Kopp, S, Langguth, P, Barends, DM, Abrahamsson, B, Nair, A, Shah, VP, Groot, DW, Dressman, JB, Zimmer, M

J Pharm Sci 2012
16943252 Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol

Tang, M, Black, C, Charpentier, N, Yan, B, Shi, D, Yang, D, Yang, J, LeCluyse, EL, Mukundan, M

J Pharmacol Exp Ther 2006
5013373 Absorption kinetics of aspirin in man following oral administration of an aqueous solution

Sholkoff, SD, Harris, PA, Riegelman, S, Rowland, M

J Pharm Sci 1972
28677105 Carboxylesterases in lipid metabolism: from mouse to human

Lian, J, Nelson, R, Lehner, R

Protein Cell 2018
16837570 Substrate specificity of carboxylesterase isozymes and their contribution to hydrolase activity in human liver and small intestine

Imai, T, Hosokawa, M, Shii, M, Chiba, K, Taketani, M

Drug Metab Dispos 2006
9144407 Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver

Schmitz, G, Becker, A, Schwer, H, Aslanidis, C, Daig, R, Langmann, T

Biochem Biophys Res Commun 1997
Catalyst Activity

carboxylic ester hydrolase activity of CES1 trimer, CES2 [endoplasmic reticulum lumen]

Orthologous Events
Cross References
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