Abstract
The regulation of metabolic networks has been shown to be distributed and shared through the action of metabolic cycles. Biochemical cycles play important roles in maintaining flux and substrate availability for multiple pathways to supply cellular energy and contribute to dynamic stability. By understanding the cyclic and acyclic flows of matter through a network, we are closer to understanding how complex dynamic systems distribute flux along interconnected pathways. In this work, we have applied a cycle decomposition algorithm to a genome-scale metabolic model of Chlamydomonas reinhardtii to analyse how acetate supply affects the distribution of fluxes that sustain cellular activity. We examined the role of metabolic cycles which explain the down regulation of photosynthesis that is observed when cells are grown in the presence of acetate. Our results suggest that acetate modulates changes in global metabolism, with the pentose phosphate pathway, the Calvin-Benson cycle and mitochondrial respiration activity being affected whilst reducing photosynthesis. These results show how the decomposition of metabolic flux into cyclic and acyclic components helps to understand the impact of metabolic cycling on organismal behaviour at the genome scale.
Highlights
It has been widely documented that cyclic structures play a central role in the homeostasis of biological systems (Qian & Beard, 2006; Cornish-Bowden & Cárdenas, 2008)
We showed that the presence of acetate in the growth medium results in a fundamental change in the primary routes of carbon metabolism, which feeds back into the reactions of photosynthesis
Triose phosphate is incorporated into metabolism by the reactions of gluconeogenesis to generate hexose sugars, which can be stored as starch reserves
Summary
It has been widely documented that cyclic structures play a central role in the homeostasis of biological systems (Qian & Beard, 2006; Cornish-Bowden & Cárdenas, 2008). The tricarboxylic acid (TCA) cycle, known as the Krebs cycle, is one of the most fundamental cycles for many species. The TCA cycle can be thought of as starting with the reaction of acetyl-CoA with oxaloacetate (OAA) producing citrate. With every turn of the cycle, the substrate OAA, a 4-carbon compound, is recycled and can be used again for subsequent cycles. As with the TCA cycle, cycles play a pivotal role of retaining substrate matter and maintaining flux availability for multiple pathways to supply the cell with energy. Cycles help maintain the organisational characteristics of a system, contributing to dynamic stability (Reznik & Segrè, 2010)
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