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. 2016 Sep 30;6:205. doi: 10.3389/fonc.2016.00205

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Copyright © 2016 Iorio, Caramujo, Cecchetti, Spadaro, Carpinelli, Canese and Podo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Links between altered glucose and phosphatidylcholine metabolism in breast cancer. Glucose metabolism occurs in cancer cells. Glycolysis is a series of metabolic processes, in which 1 mol of glucose is catabolized to 2 mol of pyruvate. As indicated, several intermediates can fuel the pentose phosphate pathway (PPP) or lead to lipid synthesis. In cancer cells, pyruvate is further converted into lactate. Pyruvate can be imported in the mitochondrial matrix to feed the tricarboxylic acid (TCA) cycle. This step is controlled by pyruvate dehydrogenase kinase (PDK), which can inactivate pyruvate dehydrogenase (PDH). Transporters: Glut, glucose transporter; MCT, monocarboxylate transporter. Metabolites: Ala, alanine; α-KG, α-ketoglutarate; DAG, diacylglycerol; G6P, glucose-6-phosphate; F6P, fructose-6-phosphate; F1,6BP, fructose-1,6-bisphosphate; DHAP, dihydroxyacetone phosphate; Gro3P, sn-glycerol-3-phosphate; GA3P, glyceraldehyde-3-phosphate; G3P, 3-phosphoglycerate; PA, phosphatidate; PEP, phosphoenolpyruvate; TAG, triacylglycerol. Enzymes: ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; HK, hexokinase; LDH, lactate dehydrogenase; PDK, pyruvate dehydrogenase kinase; PDH, pyruvate dehydrogenase phosphatidylcholine (PtdCho) cycle. Transporters: CHT1, choline high-affinity transporter-1; CTL, choline transporter-like protein; OCT2, organic cation transporter-2. Metabolites: CDP-Cho, cytidine diphosphate choline; Cho, free choline; DAG, diacylglycerol; FFA, free fatty acid; Gro3P, sn-glycerol-3-phosphate; GPCho, glycerophosphocholine; LPtdCho, lysophosphatidylcholine; PA, phosphatidate; PCho, phosphocholine. Enzymes: Kennedy pathway: ChoK, choline kinase (EC 2.7.1.32); CT, cytidylyltransferase (EC 2.7.7.15); PCT, phosphocholine transferase (EC 2.7.8.2). Headgroup hydrolysis pathways: PLC, phospholipase C (EC 3.1.4.3); PLD, phospholipase D (EC 3.1.4.4). Deacylation pathway: PLA1, phospholipase A1 (EC 3.1.1.32); PLA2, phospholipase A2 (EC 3.1.1.4); LPL, lysophospholipase (EC 3.1.1.5); PD, glycerophosphocholine phosphodiesterase (EC 3.1.4.2). Red arrows indicate direction of change in enzyme activity enzymes and metabolite content.