The esterase metabolism of the death camas alkaloids, 3-angeloylzygadenine and 3-veratroylzygadenine to zygadenine in sheep

Authors: Green, Benedict; Lee, Stephen; Stonecipher, Clinton; Welch, Kevin; Cook, Daniel

Submitted to: Translational Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2026
Publication Date: 4/11/2026
Citation: Green, B.T., Lee, S.T., Stonecipher, C.A., Welch, K.D., Cook, D. 2026. The esterase metabolism of the death camas alkaloids, 3-angeloylzygadenine and 3-veratroylzygadenine to zygadenine in sheep. Translational Animal Science. 10: Article txag045. https://doi.org/10.1093/tas/txag045.
DOI: https://doi.org/10.1093/tas/txag045

Interpretive Summary: Foothill death camas is one of about 15 death camas species in North America, that can poison grazing livestock during the early Spring when better forage is not available. We hypothesized that two death camas toxins would be rapidly metabolized by by sheep. In vitro enzyme progress curves were used to estimate Michaelis-Menten enzyme kinetic values. To confirm in vitro metabolism results, sheep were orally dosed with 0.5 g/kg dried ground death camas floral plant material and plasma alkaloid concentrations measured over 24 hours. Results of experiments documented that liver was most effective at metabolizing the toxins suggesting that in sheep, liver metabolism is the principal method of detoxification.

Technical Abstract: Foothill death camas [Zigadenus paniculatus; or Toxicoscordion paniculatum] is one of about 15 death camas species in North America that is poisonous to grazing livestock. The major toxins in death camas are zygadenine and zygacine, the 3-acetyl ester of zygadenine. However, during plant flower to seed pod growth stages, 3-angeloylzygadendine and 3-veratroylzygadenine become major alkaloids in these reproductive tissues. We hypothesized that 3-angeloylzygadendine, and 3-veratroylzygadenine would be rapidly metabolized by esterases in liver, plasma, and rumen to zygadenine. Three death camas alkaloids, zygacine (as a positive control), 3-angeloylzygadendine, and 3-veratroylzygadenine were evaluated with in vitro rumen, plasma and liver S9 incubations. Results from these experiments indicated that 3-veratroylzygadenine but not 3-angeloylzygadendine was rapidly metabolized. To confirm the in vitro metabolism results, sheep were orally dosed death camas plant material containing only the reproductive parts of the plants, blood was collected by venipuncture, and alkaloid concentrations measured. The rapid metabolism of 3-veratroylzygadenine but not 3-angeloylzygadendine was confirmed with the in vivo sheep dosing experiments, and we accepted our esterase metabolism hypothesis for 3-veratroylzygadenine.