Figure 7.
Metabolic profile changes associated with thiamine-PP depletion in TRMA (-/-) cultures exhibiting apoptosis. TRMA cells in the presence of thiamine use glucose as the major substrate for de novo nucleic acid synthesis through the nonoxidative steps of the pentose cycle (left). Nonoxidative ribose synthesis decreases while direct glucose oxidation increases in the pentose cycle (right). TCA cycle substrate flux showed no significant response to thiamine depletion indicating well-preserved pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase activities as other thiamin-dependent enzymes of metabolism. SIDMAP provides a virtual roadmap by which regulation of cell cycle, enzyme protein synthesis, as well as gene expression can be pursued for revealing the mechanism of TRMA cells' metabolic deficiencies.