CYP3A4 monooxygenates ATVL to 4-OH-ATVL

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
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
Atorvastatin lactone (ATVL) is hydroxylated to hydroxy-metabolites, predominantly by cytochrome P450 3A4 (CYP3A4) (Park et al. 2008). Statin lactones are metabolized to a much higher extent than their acid forms by CYP enzymes, suggesting that metabolism of the lactone is the relevant pathway for atorvastatin elimination (Jacobsen et al. 2000, Fujino et al. 2004, Filppula et al. 2021). Described here is the formation of 4-hydroxyatorvastatin lactone (4-OH-ATVL).
Literature References
PubMed ID Title Journal Year
34045219 Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins

Viinamäki, J, Parviainen, H, Hirvensalo, P, Niemi, M, Ivaska, VE, Filppula, AM, Kurkela, M, Deng, F, Neuvonen, M, Lönnberg, KI

Drug Metab Dispos 2021
18720283 Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin

Park, JE, Kim, KB, Moon, BS, Shin, JG, Bae, SK, Liu, KH

Xenobiotica 2008
15801541 Metabolic properties of the acid and lactone forms of HMG-CoA reductase inhibitors

Fujino, H, Sakaeda, T, Saito, T, Tsunenari, Y, Kojima, J

Xenobiotica 2004
11038166 Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin

Sewing, KF, Soldner, A, Christians, U, Jacobsen, W, Kirchner, G, Benet, LZ, Kuhn, B, Kollman, PA

Drug Metab Dispos 2000
Catalyst Activity

monooxygenase activity of CYP3A4 [endoplasmic reticulum membrane]

Orthologous Events
Cite Us!