THIAMINE-DEFICIENCY DECREASES STEADY-STATE TRANSKETOLASE AND PYRUVATE-DEHYDROGENASE BUT NOT ALPHA-KETOGLUTARATE DEHYDROGENASE MESSENGER-RNALEVELS IN 3 HUMAN CELL-TYPES

Reductions in the levels and activities of enzymes that utilize thiami ne diphosphate (ThDP) as a cofactor are thought to be responsible for the tissue damage suffered during thiamine deficiency. Although loss o f cofactor can account in part for loss of enzyme activity, thiamine a nd 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 h uman fibroblasts, lymphoblasts and neuroblastoma cells cultured under conditions of thiamine sufficiency and deficiency. In all three cell t ypes, the mRNA levels of transketolase and the E1 beta subunit of pyru vate dehydrogenase complex were lower in thiamine-deficient cultures. In contrast, mRNA levels for a ThDP-binding subunit of alpha-ketogluta rate dehydrogenase, the E1 subunit did not differ. These results indic ate that thiamine or a thiamine metabolite regulates the expression in humans of some, but not all, genes encoding ThDP-utilizing enzymes.