A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines
Fig 2
A Rank-ordered ATP yields achieved by the models describe a gradual increase rather than clusters around theoretical ATP yields. The spread of ATP yields highlights the metabolic heterogeneity between the 120 models. The cell lines use a mixture of pathways and metabolic fuels for ATP production, which explains that the predicted ATP yield can exceed the theoretical measures. Two major strategies for ATP production can be distinguished based on the ATP yields. The distinction lies in the higher contribution of either phosphoglycerate kinase (green squares) or ATP synthase (red squares) to the total ATP production. B A fine-grained division of the OxPhos models is achieved considering the production strategies of ATP, NADPH, NADH, and FADH2. The table lists the reactions contributing most to ATP, NADH, NADPH, and FADH2 production for each phenotype (I-VIII). C A three dimensional plot of the eight phenotypes with respect to the utilization of glycolysis, the TCA cycle, and oxidative phosphorylation. D Three different oxotypes are distinguished. The distinction between the OxPhos models (blue) is different from the phenotypic classification performed based on the energy and cofactor production strategies depicted above (see also S1 Text). E Six model clusters are distinguished according to each models’ ability to deal with environmental changes. Variations in glucose, glutamine, lactate, and oxygen lead to a distinct stratification of OxPhos models. Fig F in S1 Text shows different perspectives.