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. Author manuscript; available in PMC: 2010 Jul 1.
Published in final edited form as: Cancer Res. 2009 Jun 23;69(13):5467–5474. doi: 10.1158/0008-5472.CAN-08-4979

Figure 1. Reversal of CEM cell growth inhibition by AICA indicated that the second target of pemetrexed is AICART, not GART.

Figure 1

CEM cells were treated with the indicated concentrations of pemetrexed alone (A, no add) or 6R-DDATHF (B, no add) or in the presence of TdR (5.6 μM), Hx (32 μM), AICA (320 μM), or a combination of TdR with either Hx or AICA. Drug and modifying agents were added simultaneously and drug-containing medium was changed at 48 hours. Cell growth was determined after 96 hours and cell number is expressed relative to controls without drug. Panel C depicts the folate-dependent steps of de novo purine synthesis and the site of entry of AICA and AICAR into the pathway. De novo purine synthesis consists of ten sequential enzymatic reactions starting with 1-phosphoribosyl-5-pyrophosphate (PRPP) of which two, GART and AICART, are folate-dependent. The figure depicts the substrate of the GART reaction, glycinamide ribonucleotide (GAR), and the product of this reaction formylglycinamide ribonucleotide (FGAR), as well as the salvage of AICA, AICAR, and hypoxanthine catalyzed by adenine phosphoribosyltransferase (APRT), adenosine kinase (AK), and hypoxanthine-guanine phosphoribosyltransferase (HGPRT), respectively.