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This article is part of the supplement: Eighth International Conference on Bioinformatics (InCoB2009): Computational Biology

Open Access Proceedings

Human liver rate-limiting enzymes influence metabolic flux via branch points and inhibitors

Min Zhao and Hong Qu*

Author affiliations

Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, PR China

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Citation and License

BMC Genomics 2009, 10(Suppl 3):S31  doi:10.1186/1471-2164-10-S3-S31

Published: 3 December 2009

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.

Conclusion

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.