Stanic Ana, Uhlig Silvio, Solhaug Anita, Rise Frode, Wilkins Alistair L, Miles Christopher O
Norwegian Veterinary Institute , P.O. Box 750, Sentrum, NO-0106 Oslo, Norway.
Department of Chemistry, University of Oslo , P.O. Box 1033, Blindern, NO-0315 Oslo, Norway.
J Agric Food Chem. 2016 Jun 15;64(23):4777-85. doi: 10.1021/acs.jafc.6b01158. Epub 2016 Jun 3.
Conjugation with the biologically relevant thiol glutathione is one of the metabolic pathways for the mycotoxin deoxynivalenol (DON) in wheat. The occurrence of putative DON-cysteine conjugates has also been shown in wheat, likely in part as a result of degradation of the glutathione conjugates. It was reported that thiols react in vitro with DON at two positions: reversibly at C-10 of the α,β-unsaturated ketone and irreversibly at C-13 of the epoxy group. We synthesized pure DON-cysteine adducts and made analytical standards using quantitative NMR experiments. Compounds were characterized using NMR and LC-HRMS/MS and tested in vitro for toxicity. Cysteine conjugates were much less toxic than DON at the same concentration, and LC-HRMS analysis demonstrated that there was no detectable metabolism of the conjugates in human monocytes or human macrophages.
与具有生物学相关性的硫醇谷胱甘肽结合是小麦中霉菌毒素脱氧雪腐镰刀菌烯醇（DON）的代谢途径之一。在小麦中也已证实存在假定的DON-半胱氨酸共轭物，这可能部分是谷胱甘肽共轭物降解的结果。据报道，硫醇在体外与DON在两个位置发生反应：在α,β-不饱和酮的C-10处可逆反应，在环氧基的C-13处不可逆反应。我们合成了纯的DON-半胱氨酸加合物，并使用定量核磁共振实验制备了分析标准品。使用核磁共振和液相色谱-高分辨质谱/质谱对化合物进行了表征，并在体外测试了其毒性。在相同浓度下，半胱氨酸共轭物的毒性远低于DON，液相色谱-高分辨质谱分析表明，在人单核细胞或人巨噬细胞中未检测到共轭物的代谢。
