Membrane potential as a regulation mechanism of periplasmic nitrite reductase activity: a mathematical model

Periplasmic NrfA nitrite reductase is the main component of the respiratory chain in Escherichia coli during nitrite (NO$_2$) anaerobic respiration. NrfA is involved in the formation of an electron transport chain in the cell membrane necessary for the ATP synthesis; and nitrite utilization at substrate concentrations not exceeding 2 mM. Earlier, we presented a hypothesis that activity of NrfA reductase at low NO$_2$ concentrations in the medium is determined not only by the mechanisms which influence the expression of genes encoding its structure, but also by the influence of the membrane potential on the formation of the enzyme’s active form in the periplasm. To substantiate this hypothesis, we developed a model of NO$_2$ utilization by E. coli cells in a chemostat coupled with the processes of electric potential formation in the cell membrane. Due to the absence of experimental data on the structure of the electron transport chain during nitrite respiration, two hypothetical scenarios for the membrane potential formation during cell cultivation in a chemostat containing FHL-1 and FHL-2 format hydrogenelyase complexes, which include Fdh formate dehydrogenase and Hyd-3 and Hyd-4 hydrogenases, have been considered; and corresponding models were developed. It was demonstrated that inclusion in the model of nitrite utilization by E. coli cells of specific molecular genetic and metabolic processes involved in the membrane potential formation allows proper description of the experimental data on the kinetics of nitrite utilization in a chemostat. It was also shown that modeling results do not depend on the scenario of membrane potential formation. In general, the data obtained confirm the important role of the membrane potential in regulating the activity of periplasmic Nrf reductase at micromolar concentrations of nitrite in the medium. It is possible that this mechanism may be relevant for other proteins, the activity of which depends on their localization in the periplasm.