Team:IIT Delhi/modelling

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

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:

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