Perturbations to the phosphoinositide pathway. Blue lines represent experimental observations and bars represent model predictions. (a) Perturbation of PI levels, PI4K and PI5KI activities and resulting effects in PI(4,5)P2 and PI(4)P. γ→0 is decreased to 50% to trigger a decrease of 50% in PI. (b) Perturbation of input fluxes to the levels of PI(4)P and PI(4,5)P2. After stopping all inputs into PI(4)P and PI(4,5)P2, the inputs are re-activated, one at a time, to test if they are sufficient to restore PI(4,5)P2 levels. Enzyme knockouts were simulated by setting the rate constant of the corresponding flux to zero, except for γ0→4, which was decreased to 20% of its original value, in order to avoid numerical errors in the simulation due to very small levels of PI(4)P. (c) Perturbations to MTMR, SYNJ_TMEM55 and PIKfyve that were used to fit the model to the behaviour of phosphoinositides with small pools: PI5P, PI(3,5)P2 and PI(3)P. (d) Consequences of Golgi PI(4)P input (γ→4) for the levels of PI(4)P and PI(4,5)P2 pools. Golgi PI(4)P has a significant impact on the PI(4)P pool but barely affects the PI(4,5)P2 pool. The graphs were created in R42 and the x axis labels were added with PowerPoint.