Fig. 1
From: Systems analysis of intracellular pH vulnerabilities for cancer therapy
Reconstruction of enzymatic pH-dependent activity profiles. a Six critical pH points, corresponding to the 0%, 50%, and 100% of enzymatic activity at the acidic and basic regimes were extracted from BRENDA from all taxa. Missing data was complemented with existing data from close homologs or were predicted using linear regressors, generating an imputed database of pH-activity profiles, from which one infers the pH-profile of any enzyme (Methods, Supplementary Methods and Supplementary Figures 1–7 for a complete description). b Predicted vs. experimental pH optima, defined as the average of the critical points A100 and B100. The red line depicts linear regression. c Distributions of the pH optima of metabolic enzymes in each cellular compartment. Box widths are proportional to the number of enzymes in each compartment. Each box delineates lower quartile, median, and upper quartile values. Most extreme values (whiskers) are within 1.5 times the inter-quartile range from the ends of the box. Red dots depict the measured physiological pHi range of the compartment. “Including experiments” boxes correspond to the pH optima that were used in the subsequent GSMM modeling. As a validation, we include “Only predictions” boxplots, which are the result of the 10-fold cross-validation (Supplementary Figure 5)
