Suzuki Kazuo T, Somekawa Layla, Suzuki Noriyuki
Department of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Toxicol Appl Pharmacol. 2006 Oct 15;216(2):303-8. doi: 10.1016/j.taap.2006.05.016. Epub 2006 May 27.
Nutritional selenium compounds are transformed to the common intermediate selenide and then utilized for selenoprotein synthesis or excreted in urine mostly as 1beta-methylseleno-N-acetyl-Dd-galactosamine (selenosugar). Since the biological significance of selenosugar formation is unknown, we investigated their role in the formation of selenoenzymes in selenium deficiency. Rats were depleted of endogenous natural abundance selenium with a single stable isotope ((82)Se) and then made Se-deficient. (76)Se-Selenosugar was administered intravenously to the rats and their urine, serum, liver, kidneys and testes were subjected to speciation analysis with HPLC inductively coupled argon plasma mass spectrometry. Most (76)Se was recovered in its intact form (approximately 80% of dose) in urine within 1 h. Speciation analysis revealed that residual endogenous natural abundance selenium estimated by (77)Se and (78)Se was negligible and distinct distributions of the labeled (76)Se were detected in the body fluids and organs without interference from the endogenous natural abundance stable isotope. Namely, intact (76)Se-selenosugar was distributed to organs after the injection, and (76)Se was used for selenoprotein synthesis. Oxidation to methylseleninic acid and/or hydrolysis of the selenoacetal group to methylselenol were proposed to the transformation of selenosugar for the reuse. Effective use of an enriched stable isotope as an absolute label in hosts depleted of natural abundance isotopes was discussed for application in tracer experiments.
营养性硒化合物会转化为常见的中间产物硒化物,然后用于硒蛋白的合成,或者大多以1β-甲基硒代-N-乙酰-D-半乳糖胺(硒糖)的形式经尿液排出。由于硒糖形成的生物学意义尚不清楚,我们研究了它们在硒缺乏时硒酶形成中的作用。用单一稳定同位素(82Se)耗尽大鼠体内内源性天然丰度的硒,然后使其缺硒。将76Se-硒糖静脉注射给大鼠,并用高效液相色谱-电感耦合氩等离子体质谱法对其尿液、血清、肝脏、肾脏和睾丸进行形态分析。大部分76Se在1小时内以完整形式(约占剂量的80%)在尿液中回收。形态分析表明,由77Se和78Se估计的残留内源性天然丰度硒可忽略不计,并且在体液和器官中检测到标记的76Se有明显的分布,不受内源性天然丰度稳定同位素的干扰。也就是说,完整的76Se-硒糖在注射后分布到各器官,并且76Se用于硒蛋白的合成。有人提出,硒糖的转化再利用涉及氧化为甲基亚硒酸和/或将硒缩醛基团水解为甲基硒醇。讨论了在缺乏天然丰度同位素的宿主中有效使用富集稳定同位素作为绝对标记物在示踪实验中的应用。