Integrative feedback and robustness in a lipid biosynthetic network

The homeostatic control of membrane lipid composition appears to be of central importance for cell functioning and survival. However, while lipid biosynthetic reaction networks have been mapped in detail, the underlying control architecture which underpins these networks remains elusive. A key problem in determining the control architectures of lipid biosynthetic pathways, and the mechanisms through which control is achieved, is that the compositional complexity of lipid membranes makes it difficult to determine which membrane parameter is under homeostatic control. Recently, we reported that membrane stored elastic energy provides a physical feedback signal which modulates the activity in vitro of CTP:phosphocholine cytidylyltransferase (CCT), an extrinsic membrane enzyme which catalyses a key step in the synthesis of phosphatidylcholine lipids in the Kennedy pathway (Kennedy 1953 J. Am. Chem. Soc. 75, 249-250). We postulate that stored elastic energy may be the main property of membranes that is under homeostatic control. Here we report the results of simulations based on this postulate, which reveal a possible control architecture for lipid biosynthesis networks in vivo.