nitrogen metabolism of saccharomyce cervisiae a matlab numerical simulation based on the research of...
DESCRIPTION
Context and Purpose The System = The Cell Model shows change over time as related to state variables. By changing the parameters, starting concentrations, ect., my model allows observation of consequent changes in cellTRANSCRIPT
Nitrogen Metabolism of Saccharomyce cervisiae
A Matlab numerical simulation based on the research of ter Schure published in the Journal of Bacteriology and Microbiology
Sarah Carratt
BIOL 398/MATH 388Loyola Marymount University
February 24, 2011
OverviewContext and purpose for modelState variablesParametersTerms for Equations How do they fit context?Differential EquationsSimulation graphs (D=.05, .29)TrendsBrief comparison with ter Schure studies
Context and PurposeThe System = The Cell
•Model shows change over time as related to state variables.
•By changing the parameters, starting concentrations, ect., my model allows observation of consequent changes in cell
State Variables factors to watch/model as they change over time
Ammonium → nitrogen α-ketoglutarate Glutamate Glutamine
Parameters V#= indirect measure of enzyme level (ke)
GDA, GS, NAD-GDH, NADPH-GDH k# = rate constant for each enzyme Du = source, inflow (dilution rate*feed concentration)
u = nitrogen + carbon D = 1/time
Understanding the Math
V4, k4V2, k2
V3, k3 V1, k1
V5, k5 V5, k5
V5, k5V5, k5
•Adding/subtracting these terms in differential equation can show production/consumption of product
Differential Equations
dxdt(keto) = V3(mate/(k3+mate))-V4(keto/(k4+keto))dxdt(mine) = V2(mate/(k2+mate))-V1(mine/(k1+mine))dxdt(mate) =
V1(mine/(k1+mine))-V2(mate*NH4/(k2+mate*NH4))+V3(keto*NH4/(k3+keto*NH4))-V4(mate/(k4+mate))+V5(keto*mine/(k5+keto*mine))
dxdt(NH4) = D*u+V1(mine/(k1+mine))+V3(mate/(k3+mate))-V2(NH4/(k2+NH4))-V4(NH4/(k4+NH4))
Simulation at Microbiology Dilution Rates
K values= 2V values = 5u = 10t = 0-10x0 = 10 or 20
FUTURE: Expand model to provide better comparison between dilution rates and alter other variables/parameters in equations
Overview of Model“Ends” of process were mostly constant (-ketoglutarate
and glutamine)Glutamate is positive and linear
Place in metabolism/Pathways that produce glutamate in cycle
Ammonium is mostly constant Slight loss initially followed by low growth in .29 (positive trend) Steeper loss initially followed by low loss in .05 (negative trend)
FUTURE Expand model to provide better comparison between dilution
rates Alter other variables/parameters in equations
Comparision with ter Schure Papers
Microbiology Bacteriology My ModelCONSTANTS Ammonium and
glucoseAmmonium flux Ammonium and
feed concentrationCHANGES Dilution rate Ammonium
concentrationDilution rate
GOALS Determine what is the regulating factor in nitrogen metabolism.
Study transcription and effect of changing carbon and nitrogen fluxes and dilution rates.
Produce a model to illustrate interaction of the four substrates of nitrogen metabolism
•Microbiology paper helped to clarify methods of Bacteriology paper•My model shows interaction of substrates ter Schure measured
Review Model shows how state variables/substrates change over time. State variables:
Ammonium → nitrogen, α-ketoglutarate, Glutamate, Glutamine Parameters:
V, k, D, u Assigned constants to reactions and +/- in equation shows
production/consumption Simulation graphs (D=.05, .29) Trends:
Middle vs. Ends The goal was to examine the interaction of substrates in nitrogen
metabolism proposed by ter Schure studies accomplished?
References
Nitrogen-regulated transcription and enzyme activities in continuous cultures of Saccharomyces cerevisia (Microbiology, 1995, 141, pp1101-1108)
The Concentration of Ammonia Regulates Nitrogen Metabolism in Saccharomyces cerevisiae (Bacteriology, 1995, 177, no. 22, pp6672-6675)
Images from class presentations by Dr. Dahlquist and Dr. Fitzpatrick