Bettendorff L
Laboratory of Neurochemistry, University of Liège, Belgium.
Arch Physiol Biochem. 1996 Oct;104(6):745-51. doi: 10.1076/apab.104.6.745.12916.
Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha-ketoglutarate (KGDH) dehydrogenases and transketolase. Thiamine deficiency leads to reversible and irreversible brain lesions due to impaired oxidative metabolism. A specific non-cofactor role for thiamine has also been proposed in excitable cells and thiamine triphosphate (TTP) might be involved in the regulation of ion channels. Thiamine is taken up by neuroblastoma cells through a high affinity transporter. Inside the cells, it is rapidly phosphorylated to TDP. This high turnover TDP pool is the precursor for TTP. Most of the TDP however has a low turnover and is associated with PDH and KGDH in mitochondria. In excised inside-out patches from neuroblastoma cells, TTP, at a concentration of 1 microM, activates chloride channels of large unitary conductance, the so-called maxi-Cl- channels. These channels are inhibited by oxythiamine from the outide. In addition to the role of TTP in the regulation of chloride channels, thiamine itself, or a presently unknown analog, may have trophic effects on neuronal cells.
硫胺素二磷酸（TDP）是丙酮酸（PDH）、α-酮戊二酸（KGDH）脱氢酶和转酮醇酶的重要辅助因子。硫胺素缺乏会因氧化代谢受损导致可逆和不可逆的脑损伤。硫胺素在可兴奋细胞中还被认为具有特定的非辅助因子作用，且三磷酸硫胺素（TTP）可能参与离子通道的调节。神经母细胞瘤细胞通过高亲和力转运体摄取硫胺素。在细胞内，它会迅速磷酸化为TDP。这个高周转率的TDP池是TTP的前体。然而，大多数TDP周转率低，且与线粒体中的PDH和KGDH相关。在从神经母细胞瘤细胞分离出的内向外膜片中，浓度为1微摩尔的TTP可激活大单位电导的氯离子通道，即所谓的大氯离子通道。这些通道可被胞外的氧硫胺素抑制。除了TTP在调节氯离子通道方面的作用外，硫胺素本身或目前未知的类似物可能对神经元细胞具有营养作用。
