Editing Aconitine (section)

==Metabolism==
[[File:Aconine.svg|thumb|[[Aconine]]: an amorphous, bitter, non-poisonous alkaloid, derived from the decomposition of aconitine]]
Aconitine is metabolized by [[cytochrome P450]] isozymes (CYPs). There has been research in 2011 in China to investigate in-depth the CYPs involved in aconitine metabolism in human liver microsomes.<ref>{{cite journal | vauthors = Tang L, Ye L, Lv C, Zheng Z, Gong Y, Liu Z | title = Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes | journal = Toxicology Letters | volume = 202 | issue = 1 | pages = 47–54 | date = April 2011 | pmid = 21277363 | doi = 10.1016/j.toxlet.2011.01.019 }}</ref> It has been estimated that more than 90 percent  of currently available human drug metabolism can be attributed to eight main enzymes (CYP 1A2, 2C9, 2C8, 2C19, 2D6, 2E1, 3A4, 3A5).<ref>{{cite journal | vauthors = Bertilsson L, Lou YQ, Du YL, Liu Y, Kuang TY, Liao XM, Wang KY, Reviriego J, Iselius L, Sjöqvist F | title = Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin | journal = Clinical Pharmacology and Therapeutics | volume = 51 | issue = 4 | pages = 388–397 | date = April 1992 | pmid = 1345344 | doi = 10.1038/clpt.1992.38 | s2cid = 42831017 }}</ref> The researchers used [[Recombinant DNA|recombinants]] of these eight different CYPs and incubated it with aconitine. To initiate the metabolism pathway the presence of NADPH was needed. Six CYP-mediated metabolites (M1–M6) were found by [[Liquid chromatography–mass spectrometry|liquid chromatography]], these six metabolites were characterized by [[Liquid chromatography–mass spectrometry|mass-spectrometry]]. The six metabolites and the involved enzymes are summarized in the following table:
{| class="wikitable"
|-
! Metabolite!! Name !! Involved CYPs
|-
| M1 || O-Demethyl-aconitine || CYP3A4, CYP3A5, CYP2D6, CYP2C8
|-
| M2 || 16-O-Demethyl-aconitine || CYP3A4, CYP3A5, CYP2D6, CYP2C9
|-
| M3 || N-deethyl-aconitine || CYP3A4, CYP3A5, CYP2D6, CYP2C9
|-
| M4 || O-didemethyl-aconitine || CYP3A5, CYP2D6
|-
| M5 || 3-Dehydrogen-aconitine || CYP3A4, CYP3A5
|-
| M6 || Hydroxyl-aconitine || CYP3A5, CYP2D6
|}

Selective [[enzyme inhibitor|inhibitors]] were used to determine the involved CYPs in the aconitine metabolism. The results indicate that aconitine was mainly metabolized by CYP3A4, 3A5 and 2D6. CYP2C8 and 2C9 had a minor role to the aconitine metabolism, whereas CYP1A2, 2E1 and 2C19 did not produce any aconitine metabolites at all. The proposed [[metabolic pathway]]s of aconitine in human liver microsomes and the CYPs involved to it are summarized in the table above.