Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase

G. Mkrtchyan, A. Graf, L. Bettendorff, V. Bunik, Neurochemistry International, Available online 20 October 2016, ISSN 0197-0186, doi:10.1016/j.neuint.2016.10.009.

Our study points to cell-specific regulation of the thiamine-dependent metabolic network, which includes significant coupling between the OGDH reaction, often the TCA cycle “bottle neck”, and thiamine influx in normal rat brain and astrocytes. In the brain with decreased thiamine levels and/or impaired OGDH, which have been observed in aging and/or neurodegenerative diseases, such coupling may require thiamine levels exceeding those known to saturate the ThDPdependent enzymes under normal conditions. The findings may justify therapeutic application of high doses of thiamine in patients with neurodegenerative diseases.

 Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase