PRKAA2 and leukemia: Thus, pemetrexed has been shown to activate AMPK in leukaemia cells due to inhibition of AICAR transformylase and consequent accumulation of its substrate ZMP [93], while in HEK-293 cells, where AICA riboside has little effect on its own because of rapid metabolism of ZMP by AICAR transformylase, the ribonucleoside does activate AMPK dramatically in the presence of the AICAR transformylase inhibitor, methotrexate [94].