Lei-Han Tang Department of Physics, Hong Kong Baptist University CAS-MPG Partner Institute for Computational Biology, Shanghai 18-19 July, 2008 Quantitative System Biology 2008 Organization and simplification of Organization and simplification of metabolic networks metabolic networks Metabolic modeling Network simplification Small compound regulation from BRENDA Summary and future work
26
Embed
Organization and simplification of metabolic networks · Metabolic network topology can be greatly simplified when viewed in terms of vertical links (pathways) and horizontal couplings
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Lei-Han Tang
Department of Physics, Hong Kong Baptist University
CAS-MPG Partner Institute for Computational Biology, Shanghai 18-19 July, 2008Quantitative System Biology 2008
Organization and simplification ofOrganization and simplification ofmetabolic networksmetabolic networks
Metabolic network topology can be greatly simplified whenviewed in terms of vertical links (pathways) and horizontalcouplings (currencies, carriers, etc.)
Modular structure (in the form of subnets) emerge naturallyafter course-graining.
Branch points, cycles, and entry and exit points of metabolicflow clearly visible.
Summary: Some global properties of themetabolic network
End product inhibitionInterlocking regulatory interactionsin the biosynthesis of several aminoacids from aspartate
DAPDC
Metabolic network topology can be greatly simplified whenviewed in terms of vertical links (pathways) and horizontalcouplings (currencies, carriers, etc.)
Modular structure (in the form of subnets) emerge naturally aftercourse-graining.
Allosteric regulatory interactions mirror separation of horizontal(global) and vertical (pathway) metabolic flows.
Concentration of end point compounds controlled throughfeedback inhibition.
Interlocked regulation not yet quantified.
Summary: Some global properties of themetabolic network
Understand the functional role of local regulatory motifs
Detailed kinetic modelling of subnets and comparison withisotope measurement of metabolic intermediates
Regulation of global resources: homeostasis of ATP/ADP,NAD/NADH, etc.
Regulation as a means to achieve optimization? (detailedcomparison with FBA)
Km: desired compound levels, branch point regulation
Future work
E. Levine and T. Hwa (2007) Stochastic fluctuations in metabolic pathways,PNAS 104, 9224-9229.