Robust Control of PEP Formation Rate in the Carbon Fixation Pathway of C 4 Plants by a Bi-functional Enzyme

Yuval Hart, Avraham E. Mayo, Ron Milo, Uri Alon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: C 4 plants such as corn and sugarcane assimilate atmospheric CO 2 into biomass by means of the C 4 carbon fixation pathway. We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a precise rate, regulated by light, despite fluctuations in substrate and enzyme levels constituting and regulating this process.Results: We present a putative mechanism for robustness in C 4 carbon fixation, involving a key enzyme in the pathway, pyruvate orthophosphate dikinase (PPDK), which is regulated by a bifunctional enzyme, Regulatory Protein (RP). The robust mechanism is based on avidity of the bifunctional enzyme RP to its multimeric substrate PPDK, and on a product-inhibition feedback loop that couples the system output to the activity of the bifunctional regulator. The model provides an explanation for several unusual biochemical characteristics of the system and predicts that the system's output, phosphoenolpyruvate (PEP) formation rate, is insensitive to fluctuations in enzyme levels (PPDK and RP), substrate levels (ATP and pyruvate) and the catalytic rate of PPDK, while remaining sensitive to the system's input (light levels).Conclusions: The presented PPDK mechanism is a new way to achieve robustness using product inhibition as a feedback loop on a bifunctional regulatory enzyme. This mechanism exhibits robustness to protein and metabolite levels as well as to catalytic rate changes. At the same time, the output of the system remains tuned to input levels.

Original languageAmerican English
Article number171
JournalBMC Systems Biology
Volume5
DOIs
StatePublished - 24 Oct 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank our lab members for fruitful discussions. YH thanks Naama Barkai and Tsvi Tlusty for insightful comments. This work was supported by the European Research Council, and the Israel Science Foundation.

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