Abstract

Oxythiamine (OT) and 3-deazathiamine (DAT) are the antimetabolites of thiamine. The aim of study was to compare the effects of OT and DAT pyrophosphates (-PP) on the kinetics of mammalian pyruvate dehydrogenase complex (PDHC) and the in vitro culture of HeLa cells. The kinetic study showed that 3-deazathiamine pyrophosphate (DATPP) was a much stronger competitive inhibitor (K_i = 0.0026 μM) of PDHC than OTPP (K_i = 0.025 μM). Both K_i values were much lower versus K _m for thiamine pyrophosphate (0.06 μM). However, DATPP added to the culture medium for the HeLa cells culture did not hamper the rate of cell growth and showed not significant impact on the viability of the cells, whereas OTPP and OT showed a significant cytostatic effect. The differences between the thiamine antivitamins in their effect on cell growth in vitro may be due to differences in physicochemical properties and difficulty in DAT transport across the cell membrane.

摘要

氧胺（OT）和3-脱氮硫胺（DAT）是硫胺的抗代谢物。研究的目的是比较OT和DAT焦磷酸盐（-PP）对哺乳动物丙酮酸脱氢酶复合物（PDHC）动力学和HeLa细胞体外培养的影响。动力学研究表明，3-脱氮杂胺焦磷酸（DATPP）是PDHC的竞争性抑制剂（K _i = 0.0026μM）比OTPP（K _i = 0.025μM）强得多。两个K _i 值都比K _m低得多硫胺素焦磷酸（0.06μM）。但是，在HeLa细胞培养的培养基中添加DATPP不会影响细胞的生长速度，并且对细胞的活力没有显着影响，而OTPP和OT则显示出显着的细胞抑制作用。硫胺素类抗维生素在体外对细胞生长的影响上的差异可能是由于理化性质的差异以及DAT跨细胞膜转运的困难。