Foster S J, Kraus R J, Ganther H E
Arch Biochem Biophys. 1986 May 15;247(1):12-9. doi: 10.1016/0003-9861(86)90527-8.
The 24-h respiratory excretion of dimethyl selenide (DMSe) and urinary excretion of trimethylselenonium (TMSe) were studied in adult male rats injected with 2 mg Se/kg as selenobetaine [(CH3)2Se+CH2COOH] or its methyl ester, labeled with 75Se and 14C. The DMSe was trapped by means of 20% benzyl chloride in xylene. TMSe was measured by cation exchange high performance liquid chromatography. There was extensive respiratory excretion of DMSe from selenobetaine methyl ester (about 50% of the dose) and from selenobetaine (about 25%). About 12% of the dose was converted to TMSe for both compounds. When the Se-methyl carbons were labeled with 14C and the selenium with 75Se, doubly labeled DMSe and TMSe were formed; the 14C/75Se ratio in DMSe formed from selenobetaine methyl ester was almost unchanged from that administered, and the ratio in TMSe was only slightly lower than in DMSe. In contrast to its ester, doubly labeled selenobetaine yielded DMSe having a lower 14C/75Se ratio (approximately one-half of that administered) and a further decrease was observed between DMSe and TMSe. These data indicate that the (CH3)2Se moiety in selenobetaine methyl ester undergoes facile release to form DMSe, which is directly methylated to form TMSe. Selenobetaine, however, appears to lose a methyl group prior to scission of the Se-CH2COOH bond. The results with selenobetaine also suggest that TMSe generated metabolically is not inert, and can undergo demethylation followed by remethylation; confirmatory evidence for this metabolic instability is provided by the exhalation of [75Se]DMSe after the direct administration of [75Se]TMSe. When [75Se]selenobetaine or its ester was given with the methylene carbon in the acetic acid moiety labeled with 14C, only 75Se was present in the DMSe and TMSe, indicating that TMSe did not arise by decarboxylation of selenobetaine. It is concluded that both selenobetaine and its methyl ester are readily converted to DMSe and TMSe by pathways that do not involve decarboxylation or the formation of hydrogen selenide as an intermediate, and DMSe is a direct precursor of TMSe.
以75Se和14C标记的硒代甜菜碱[（CH3）2Se+CH2COOH]或其甲酯，以2mg硒/千克的剂量给成年雄性大鼠注射，研究了二甲基硒（DMSe）的24小时呼吸排泄和三甲基硒离子（TMSe）的尿液排泄。DMSe通过20%的苄基氯在二甲苯中进行捕获。TMSe通过阳离子交换高效液相色谱法进行测定。硒代甜菜碱甲酯（约占剂量的50%）和硒代甜菜碱（约占25%）有大量的DMSe通过呼吸排泄。两种化合物约12%的剂量转化为TMSe。当硒甲基碳用14C标记，硒用75Se标记时，形成了双标记的DMSe和TMSe；由硒代甜菜碱甲酯形成的DMSe中的14C/75Se比值与给药时几乎没有变化，而TMSe中的该比值仅略低于DMSe。与其酯不同，双标记的硒代甜菜碱产生的DMSe的14C/75Se比值较低（约为给药值的一半），并且在DMSe和TMSe之间观察到进一步降低。这些数据表明，硒代甜菜碱甲酯中的（CH3）2Se部分容易释放形成DMSe，DMSe直接甲基化形成TMSe。然而，硒代甜菜碱似乎在Se-CH2COOH键断裂之前失去一个甲基。硒代甜菜碱的结果还表明，代谢产生的TMSe并非惰性，可经历去甲基化然后再甲基化；直接给予[75Se]TMSe后呼出[75Se]DMSe，为这种代谢不稳定性提供了确证。当[75Se]硒代甜菜碱或其酯与乙酸部分的亚甲基碳用14C标记一起给药时，DMSe和TMSe中仅存在75Se，表明TMSe不是由硒代甜菜碱脱羧产生的。得出的结论是，硒代甜菜碱及其甲酯都能通过不涉及脱羧或形成硒化氢作为中间体的途径迅速转化为DMSe和TMSe，并且DMSe是TMSe的直接前体。
