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type: SBMLModel
species: 191775
reaction: 191975
area units: metaid_0000005
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
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is version of: ko00020
reaction: 192135
units def: metaid_0000031
species: 191795
time units: 924029
created:
  W3 CDTF: Fri Sep 29 23:49:52 BST 2006
species: 191715
modified:
  W3 CDTF: Thu Jul 05 15:45:35 BST 2012
creator:
  ORG:
    orgname: University of Pune
  n:
    given: Vivek Kumar
    family: Singh
species: 191915
species: 191735
reaction: 191995
is described by: http://identifiers.org/pubmed/16887020
reaction: 192075
reaction: 192055
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is homolog to: REACT 1785
reaction: 192115
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substance units: 924053
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creator:
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    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
reaction: 192015
species: 191895
species: 191835
reaction: 192095
occurs in: http://identifiers.org/taxonomy/1773
name: Singh2006_TCA_mtu_model2
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reaction: 192195
reaction: 192175
reaction: 192155
reaction: 192235
notes: This a model from the article: Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets. Singh VK , Ghosh I Theor Biol Med Model 2006 Aug 3;3:27 16887020 , Abstract: BACKGROUND: Targeting persistent tubercule bacilli has become an important challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass is essential for persistent bacilli, interference with it holds the potential for designing new antibacterial drugs. We have developed kinetic models of the tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and Mycobacterium tuberculosis, and studied the effects of inhibition of various enzymes in the M. tuberculosis model. RESULTS: We used E. coli to validate the pathway-modeling protocol and showed that changes in metabolic flux can be estimated from gene expression data. The M. tuberculosis model reproduced the observation that deletion of one ofthe two isocitrate lyase genes has little effect on bacterial growth in macrophages, but deletion of both genes leads to the elimination of the bacilli from the lungs. It also substantiated the inhibition of isocitrate lyases by 3-nitropropionate. On the basis of our simulation studies, we propose that: (i) fractional inactivation of both isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 is required for a flux through the glyoxylate bypass in persistent mycobacteria; and (ii) increasing the amount of active isocitrate dehydrogenases can stop the flux through the glyoxylate bypass, so the kinase that inactivates isocitrate dehydrogenase 1 and/or the proposed inactivator of isocitrate dehydrogenase 2 is a potential target for drugs against persistent mycobacteria. In addition, competitive inhibition of isocitrate lyases along with a reduction in the inactivation of isocitrate dehydrogenases appears to be a feasible strategy for targeting persistent mycobacteria. CONCLUSION: We used kinetic mode…
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