Competitive inhibition can linearize dose-response and generate a linear rectifier.
Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
Yonatan
Y
Savir
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.
Benjamin P
BP
Tu
Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
Michael
M
Springer
Competitive inhibition; Enzyme kinetics; Linear rectifiers; SAGA; Transcriptional regulation