Fig. 10

Schematic representation of different metabolic responses in acquiring FK866 resistance in CEM RES (a) and MDA RES (b) cells. CEM RES cells are NAPRT-negative and QPRT-positive cells and appear to increase the de novo pathway for NAD production. The metabolic resistance of CEM is more dependent on glycolysis and LDHA activity whereas MDA RES shows very low level of QPRT and primarily rely on LDHA activity for its resistance to FK866. The small molecules having a pro-death pharmacological effect are indicated in green. Abbreviations: NAD, nicotinamide adenine dinucleotide; NA, nicotic acid; NAMN, nicotinic acid mononucleotide; NAAD, nicotinic acid adenine dinucleotide, NAPRT, nicotinic acid phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenylyltransferase; NADS, NAD synthase; NAM, nicotinamide; NMN, nicotinamide mononucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NR, nicotinamide riboside; NRK, nicotinamide riboside kinase; QPRT, quinolinate phosphoribosyltransferase; HK, hexokinase; PFK, phosphofructokinase; PK, pyruvate kinase; LDH, lactate dehydrogenase; Gln, glutamine; Glu, glutamic acid; GSK, LDHA inhibitor; 2DG, 2-deoxyglucose; JPH, JPH203; L-Asp, l-asparaginase; GSK, GSK2837808A; LAT1, L-type amino acid transporter 1