Suzuki Kazuo T, Somekawa Layla, Kurasaki Kazuki, Suzuki Noriyuki
Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba 260-8675, Japan.
Toxicol Appl Pharmacol. 2006 Nov 15;217(1):43-50. doi: 10.1016/j.taap.2006.07.006. Epub 2006 Jul 28.
Nutritional selenocompounds are transformed into the assumed common intermediate selenide, which is utilized for the synthesis of selenoenzymes or transformed into methylated metabolites for excretion. Hence, selenocompound metabolites can be traced only with labeled selenium. Here we applied a new tracer method for the metallomics of biometals using simultaneous speciation of each metallome labeled with different homo-elemental isotopes to metabolism and availability of selenium. Rats were depleted of endogenous natural abundance selenium by feeding a single selenium stable isotope ((82)Se-selenite) and then administered (76)Se-selenite and (77)Se-selenomethionine ((77)Se-SeMet)simultaneously. Biological samples were subjected to quantification and speciation analysis by HPLC-ICPMS. Metabolites of the labeled (76)Se and (77)Se and interaction with endogenous selenium were traced and examined without interference from the corresponding endogenous natural abundance isotopes. Differences in the distribution and metabolism among organs and between the two nutritional selenocompounds were compared under exactly identical biological and analytical conditions: (1) selenite was distributed more efficiently than SeMet in organs and body fluids except the pancreas. (2) SeMet was taken up by organs in its intact form. (3) Selenium of SeMet origin was distributed selectively in the pancreas and mostly bound to a protein together with intact SeMet. (4) Selenosugars A and B but not trimethylselenonium (TMSe) were detected in the liver. (5) Selenosugar B and TMSe were detected in the kidneys.
营养性含硒化合物会转化为假定的常见中间产物硒化物,该硒化物可用于合成硒酶,或转化为甲基化代谢产物以供排泄。因此,只有使用标记的硒才能追踪含硒化合物的代谢产物。在此,我们应用了一种新的示踪方法用于生物金属的金属组学研究,该方法通过同时对用不同同素元素同位素标记的每个金属组进行形态分析,来研究硒的代谢和有效性。通过喂食单一的硒稳定同位素((82)Se-亚硒酸盐)使大鼠体内的内源性天然丰度硒耗竭,然后同时给大鼠施用(76)Se-亚硒酸盐和(77)Se-硒代蛋氨酸((77)Se-SeMet)。生物样品通过高效液相色谱-电感耦合等离子体质谱法进行定量和形态分析。在不受相应内源性天然丰度同位素干扰的情况下,追踪并检查了标记的(76)Se和(77)Se的代谢产物以及它们与内源性硒的相互作用。在完全相同的生物学和分析条件下,比较了各器官之间以及两种营养性含硒化合物之间在分布和代谢上的差异:(1) 除胰腺外,亚硒酸盐在器官和体液中的分布比硒代蛋氨酸更有效。(2) 硒代蛋氨酸以完整形式被器官摄取。(3) 源自硒代蛋氨酸的硒选择性地分布在胰腺中,并且大多与完整的硒代蛋氨酸一起与一种蛋白质结合。(4) 在肝脏中检测到了硒糖A和B,但未检测到三甲基硒离子(TMSe)。(5) 在肾脏中检测到了硒糖B和TMSe。