Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, PR China.
BMC Genomics. 2009 Dec 3;10 Suppl 3(Suppl 3):S31. doi: 10.1186/1471-2164-10-S3-S31.
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.
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.
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.
限速酶由于其相对较低的速度，被认为会影响代谢途径中的代谢通量。为了研究限速酶在代谢网络中的调节作用，我们观察了人肝脏中限速酶与分支代谢物和酶抑制剂等化合物之间的全局组织和相互作用。
基于人肝脏中的 96 种限速酶和 132 种分支点化合物，我们发现限速酶围绕着 76.5%的分支点。在人肝脏中的化合物转化网络中，涉及的 128 个分支点整体表现出更高的平均度数、中间中心性和接近中心性。近一半的体内抑制剂是限速酶的产物，覆盖了代谢抑制网络中 75.34%的抑制靶标。
从全局拓扑结构来看，限速酶整体上包围了大部分分支点；因此，它们可以影响分支点的通量。由于近一半的体内酶抑制剂是由人肝脏中的限速酶产生的，这些酶可以通过它们的天然产物引发抑制调节，从而影响代谢通量。
