%0 Journal Article
%T Robust Control of PEP Formation Rate in the Carbon Fixation Pathway of C4 Plants by a Bi-functional Enzyme
%A Yuval Hart
%A Avraham E Mayo
%A Ron Milo
%A Uri Alon
%J BMC Systems Biology
%D 2011
%I BioMed Central
%R 10.1186/1752-0509-5-171
%X We present a putative mechanism for robustness in C4 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).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.A class of biological circuits was recently described with robust input-output relations [1-4]. In these systems, the output, such as the concentration or activity of a specific protein, is perfectly insensitive to variations in the concentrations of all of the system's components, and yet responsive to the system's input. Such robust input-output relations are difficult to achieve, because in most conceivable mechanisms the output is sensitive to variations in the concentrations of the circuit components.At the heart of these robust mechanisms are bifunctional enzymes that catalyze two opposing reactions. The first example analyzed in detail appears in bacterial two-component signaling systems, in which a bifunctional receptor confers a robust input-output relationship by acting as both a kinase and a phosphatase of a response-regulator protein [1
%U http://www.biomedcentral.com/1752-0509/5/171