Detecting and investigating substrate cycles in a genome-scale human metabolic network


Substrate cycles, also known as futile cycles, are cyclic metabolic routes that dissipate energy by hydrolysing cofactors such as ATP. They were first described in the 1970s occurring in muscles of bumblebees and brown adipose tissue. A popular example is the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate and back. In this work, we analyse a large number of substrate cycles in human metabolism, which are consuming ATP and discuss their statistics. For this purpose we use two recently published methods, EFMEvolver and the K-shortest EFM method, to calculate samples of 100,000 and 15,000 substrate cycles, respectively. We find a surprisingly high number of substrate cycles in human metabolism, with up to one hundred reactions per cycle, utilizing reactions from through up to six different compartments. An analysis of tissue specific models of liver and brain metabolism shows that there is selective pressure acting against the uncontrolled dissipation of energy by avoiding the coexpression of enzymes belonging to the same substrate cycle. This selective force is particular strong against futile cycles that have a high flux due to thermodynamic principles.


Projects: A1.1: Central liver metabolism and its regulation under nutritional chal...

The FEBS journal
FEBS J. 279(17): 3192-202
11th Jul 2012

Juliane Gebauer, Stefan Schuster, Luís F de Figueiredo, Christoph Kaleta

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[Stefan Schuster]

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  • Created: 1st Aug 2012 at 11:45
  • Last updated: 24th Oct 2013 at 16:16

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