Pekovich S R, Martin P R, Singleton C K
Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235, USA.
J Nutr. 1998 Apr;128(4):683-7. doi: 10.1093/jn/128.4.683.
Reductions in the levels and activities of enzymes that utilize thiamine diphosphate (ThDP) as a cofactor are thought to be responsible for the tissue damage suffered during thiamine deficiency. Although loss of cofactor can account in part for loss of enzyme activity, thiamine and its phosphorylated derivatives may also regulate the expression of the genes encoding these proteins. To examine this possibility, steady-state mRNA levels for three ThDP-dependent enzymes were measured in human fibroblasts, lymphoblasts and neuroblastoma cells cultured under conditions of thiamine sufficiency and deficiency. In all three cell types, the mRNA levels of transketolase and the E1beta subunit of pyruvate dehydrogenase complex were lower in thiamine-deficient cultures. In contrast, mRNA levels for a ThDP-binding subunit of alpha-ketoglutarate dehydrogenase, the E1 subunit did not differ. These results indicate that thiamine or a thiamine metabolite regulates the expression in humans of some, but not all, genes encoding ThDP-utilizing enzymes.
人们认为，以硫胺素二磷酸（ThDP）作为辅因子的酶的水平和活性降低是硫胺素缺乏时组织损伤的原因。虽然辅因子的丧失可部分解释酶活性的丧失，但硫胺素及其磷酸化衍生物也可能调节编码这些蛋白质的基因的表达。为了检验这种可能性，在硫胺素充足和缺乏条件下培养的人成纤维细胞、淋巴母细胞和神经母细胞瘤细胞中，测定了三种依赖ThDP的酶的稳态mRNA水平。在所有三种细胞类型中，硫胺素缺乏的培养物中转酮醇酶和丙酮酸脱氢酶复合物E1β亚基的mRNA水平较低。相比之下，α-酮戊二酸脱氢酶的ThDP结合亚基E1亚基的mRNA水平没有差异。这些结果表明，硫胺素或硫胺素代谢物调节人类中一些（但不是全部）编码利用ThDP的酶的基因的表达。
