title: Human liver rate-limiting enzymes influence metabolic flux via branch points and inhibitors.
abstract: BACKGROUND
  Rate-limiting enzymes, because of their relatively low velocity, are believed to influence metabolic flux in pathways. To investigate their regulatory role in metabolic networks, we look at the global organization and interactions between rate-limiting enzymes and compounds such as branch point metabolites and enzyme inhibitors in human liver.
  
  
  RESULTS
  Based on 96 rate-limiting enzymes and 132 branch point compounds from human liver, we found that rate-limiting enzymes surrounded 76.5% of branch points. In a compound conversion network from human liver, the 128 branch points involved showed a dramatically higher average degree, betweenness centrality and closeness centrality as a whole. Nearly half of the in vivo inhibitors were products of rate-limiting enzymes, and covered 75.34% of the inhibited targets in metabolic inhibitory networks.
  
  
  CONCLUSIONS
  From global topological organization, rate-limiting enzymes as a whole surround most of the branch points; so they can influence the flux through branch points. Since nearly half of the in vivo enzyme inhibitors are produced by rate-limiting enzymes in human liver, these enzymes can initiate inhibitory regulation and then influence metabolic flux through their natural products.
authors: Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, PR China. zhaom@mail.cbi.pku.edu.cn
authors: Min
authors: M
authors: Zhao
authors: Hong
authors: H
authors: Qu
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D053858:Metabolic Networks and Pathways / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors