Difference between revisions of "Team:IIT Delhi/modelling"

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<img style="margin-left:50%;height:100px;width:500px;" src="https://static.igem.org/mediawiki/2015/8/8f/Imagem3_iitd.png" alt="equation1"><br/>
 
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<h2 style="font-family: 'Roboto', sans-serif;color:white;font-size:150%;text-align:center;">The rest of the reactions in this pathway are assumed to proceed via Henri-Michaelis-Menten kinetics: </h2><br/>
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<h2 style="font-family: 'Roboto', sans-serif;color:white;font-size:150%;text-align:center;border:none">The rest of the reactions in this pathway are assumed to proceed via Henri-Michaelis-Menten kinetics: </h2><br/>
 
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<h2 style="font-family: 'Roboto', sans-serif;color:white;font-size:150%;text-align:center;border:none">Km and Vmax values of hydroxymethylbilane synthase:</h2><br/><br/>
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After putting in the rate laws and the values of various parameters in Copasi software, following graphs were obtained for the concentrations and rate of formation of various species involved (Copasi has been used for obtaining all graphs and mathematical equations):
 
<a href="https://static.igem.org/mediawiki/2015/7/7a/Modelling_report_iitd.pdf" target="_blank">
 
<a href="https://static.igem.org/mediawiki/2015/7/7a/Modelling_report_iitd.pdf" target="_blank">
 
Click here to read more:
 
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Revision as of 12:58, 18 September 2015

Introduction

Three of the proteins required in the project are cytochrome c proteins (haem proteins). Hence, the heme biosynthesis pathway needs to be modelled. Pathway of heme production in E. coli (C-5 pathway from glutamate)

Mathematical model

Pathway of heme production in E. coli (C-5 pathway from glutamate):
Also, d-Aminolevulinate (ALA) produced as an intermediate in the above reactions. -Aminolevulinate Synthase (ALA Synthase) is the committed step of the heme synthesis pathway, and is usually rate-limiting for the overall pathway. Regulation occurs through control of gene transcription. Heme functions as a feedback inhibitor, repressing transcription of the gene for -Aminolevulinate Synthase.
A non-competitive irreversible feedback inhibition model is assumed for this step with a Ki value of 0.02 mM. Hence, the following equation governs the production of ALA:



equation1

The rest of the reactions in this pathway are assumed to proceed via Henri-Michaelis-Menten kinetics:





Enzyme Km (micromol/l)
Uroporphyrinogen decarboxylase ( hemE) 6.0
Coproporphyrinogen iii dehydrogenase 210
Protoporphyrinogen dehydrogenase (HemG) 7
Ferrochelatase(hemH) 4.7
Glutamate-tRNA synthase 1.9
Glutamate-1-semialdehyde 2,1-aminomutase 46
Porphobilinogen synthase 800



Km and Vmax values of hydroxymethylbilane synthase:



A non-competitive irreversible feedback inhibition model is assumed for this step with a ki value of 0.02 mM. Hence, the following equation governs the conversion to ALA:





After putting in the rate laws and the values of various parameters in Copasi software, following graphs were obtained for the concentrations and rate of formation of various species involved (Copasi has been used for obtaining all graphs and mathematical equations): Click here to read more: