a, Heatmap showing the relative concentration of 418 metabolites detected in 20 primary ccRCC tumours and adjacent normal kidneys. Metabolites were extracted from frozen tissue samples and analysed by the Thermo-Finnigan GC-MS and LC-MS/MS systems. Raw data of each metabolite was rescaled to set the median equal to 1. All metabolites were clustered according to their related pathways (based on KEGG) and then plotted as a heatmap. b, Metabolic genes involved in “carbohydrate storage” differentially expressed in ccRCC tumour vs. normal tissue. G6PC, glucose-6-phosphatase, catalytic subunit; PCK1, phosphoenolpyruvate carboxykinase 1; FBP1, fructose-1, 6-bisphosphatase 1. c, Illustration of central carbon metabolism, including glycolysis, gluconeogenesis, pentose phosphate pathway, and the TCA cycle. Enzymes controlling glycolysis (HK, hexokinase; PFK, phosphofructokinase; PKM, pyruvate kinase type M) are highlighted in red, while enzymes controlling gluconeogenesis (G6P, glucose-6-phosphatase; FBP, fructose-1, 6-bisphosphatase; PCK, phosphoenolpyruvate carboxykinase) are highlighted in green. G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; F-1, 6-BP, fructose 1, 6-bisphosphate; DHAP, dihydroxyacetone phosphate; GAP, glyceraldehyde 3-phosphate; R5P, ribose 5-phosphate; X5P, xylulose 5-phosphate; E4P, erythrose 4-phosphate; S7P, sedoheptulose 7-phosphate; PEP, phosphoenolpyruvate; Pyr, pyruvate; Ac-CoA, acetyl-CoA; Lac, lactate; Cit, citrate; αKG, alpha-ketoglutarate; Glu, glutamate; Suc, succinate; Fum, fumarate; Mal, malate; Oac, oxaloacetate; Asp, aspartate; G-SH, reduced glutathione.