TY - JOUR T1 - Design principles of autocatalytic cycles constrain enzyme kinetics and force over-expression at flux branch points JF - bioRxiv DO - 10.1101/074641 SP - 074641 AU - Uri Barenholz AU - Dan Davidi AU - Ed Reznik AU - Yinon Bar-On AU - Niv Antonovsky AU - Elad Noor AU - Ron Milo Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/11/074641.abstract N2 - A set of chemical reactions that require a metabolite to synthesize more of that metabolite is an autocatalytic cycle. Such metabolic designs must meet specific conditions to support stable fluxes, hence avoiding depletion of intermediate metabolites. Here we show that most of the reactions in central carbon metabolism are part of compact autocatalytic cycles. As such, they are subjected to constraints that may seem irrational: the enzymes of branch reactions out of the cycle must be overexpressed and the affinity of these enzymes to their substrates must be relatively low. We use recent quantitative proteomics and fluxomics measurements to show that the above conditions hold for all functioning cycles in central carbon metabolism of E.coli. This work demonstrates that the topology of a metabolic network can shape kinetic parameters of enzymes and lead to apparently reduced enzyme efficiency. ER -