DynamicsimulationsontheArachidonicAcidMetabolicNe：对花生四烯酸代谢网络的动态模拟.docVIP

Dynamic simulations on the Arachidonic Acid Metabolic Network Kun Yang1,2, Wenzhe Ma1,2, Huanhuan Liang1, Qi Ouyang2, Chao Tang2, Luhua Lai1,2* 1Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. 2Center for Theoretical Biology, Peking University, Beijing 100871, China Protocol S1 The arachidonic acid (AA) metabolic network in human PMNs was constructed based on the published experimental data[1-22] (Fig.S1). A mathematical model has been set up to simulate the dynamic properties of the network and assist the anti-inflammatory drug design approaches. The calculation curves of LTB4 and ω-LTB4 production were fitted to the experimental data. The ordinary differential equations used in the model are shown below. The serial number of products, enzymes and feedback regulations is defined in Figure S1 and the values of dynamic parameters used in the simulation are listed in Table S1 and Table S2. Figure S1. The arachidonic acid metabolic network in human PMNs. Metabolites (green), enzymes (blue) and feedback regulations (brown) are numbered for ordinary differential equations in SBML model. References 1. Wijkander J, OFlaherty JT, Nixon AB, Wykle RL (1995) 5-Lipoxygenase products modulate the activity of the 85-kDa phospholipase A2 in human neutrophils. J Biol Chem 270: 26543-26549. 2. Serio KJ, Baker JR, Ring WL, Riddick CA, Bigby TD (1997) Leukotriene B4 costimulates 5-lipoxygenase activity in neutrophils via increased 5-lipoxygenase translocation. Am J Physiol 272: C1329-1334. 3. Petrich K, Ludwig P, Kuhn H, Schewe T (1996) The suppression of 5-lipoxygenation of arachidonic acid in human polymorphonuclear leucocytes by the 15-lipoxygenase product (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid: structure-activity relationship a