Glucose-derived pyruvate provides 2 carbons to the TCA cycle when pyruvate is metabolised by pyruvate dehydrogenase (PDH; catalysis pyruvate to acetyl CoA reaction), but adds 3 carbons via pyruvate carboxylase (PC; catalysis carboxylation of pyruvate to form oxaloacetate), with both reactions upregulated in primary leukaemia cells12. Here, PC is linked to leukemia.