Fig 6. Diagrams illustrating biochemical mechanisms that could give rise to the observed correlations between metabolites.

(A) Glycolytic products. The enzymes driving relevant reactions are: 1, lactate dehydrogenase; 2, alanine aminotransferase; 3, glutamine synthetase; 4, glutaminase. (B) Glutaminolysis pathway to bypass PKM2 inhibition. Active enzymes are: 1, glutaminase; 2, aspartate aminotransferase; 3, malate dehydrogenase; 4, malate decarboxylase. (C) Correlations involving the creatine pool. Dashed boxes indicate pools of metabolites: tCr, total creatines (creatine + phosphocreatine); tCho, total cholines (choline + phosphocholine + glycerophosphocholine). The enzyme creatine kinase is marked by the number 1. (D) Correlations involving the choline pool. Dashed boxes indicate pools of metabolites: tCr, total creatines (creatine + phosphocreatine); tCho, total cholines (choline + phosphocholine + glycerophosphocholine); tGlut, glutamate + glutamine pool; PtdCho, phosphatidylcholine. The enzymes marked are: 1, choline kinase; 2, CTP:phosphocholine cytidylyltransferase and choline phosphotransferase; 3, phospholipase Al; phospholipase A2, and lysophospholipase; 4, GPC:choline phosphodiesterase. Metabolites that were not detected by the ¹H HR-MAS NMR are shown in grey. Positive correlations are shown in red while negative correlations are in blue.