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albert1

albert1

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vAKc

adenylate kinase cytosol

species_3 + species_6 = {2.0}species_2

vAKg

adenylate kinase glycosome

species_11 + species_13 = {2.0}species_12

vALD

aldolase

species_16 = species_17 + species_18

vANTI

gly3p dhap antiporter

species_22 + species_8 = species_9 + species_17

vAU

atp utilisation

species_3 > species_2

vENO

enolase

species_5 = species_4

vGAPDH

glyceraldehyde3phosphatedehydrogenase

species_18 + species_19 = species_21 + species_20

vGK

glycerol kinase

species_22 + species_12 = species_24 + species_11

vGPDH

glycerol3phosphatedehydrogenase

species_17 + species_20 = species_19 + species_22

vGPO

glycerol3phosphate oxidase

species_9 > species_8

vGT

glucose transport

species_25 = species_10

vGlyT

glycerol transport

species_24 = species_27

vHK

hexokinase

species_10 + species_11 = species_14 + species_12

vPFK

phophofructokinase

species_15 + species_11 = species_16 + species_12

vPGI

phosphoglycerate isomerase

species_14 = species_15

vPGK

phosphoglycerate kinase

species_21 + species_12 = species_23 + species_11

vPGM

phosphoglycerate mutase

species_7 = species_5

vPGT

3phosphoglycerate transport

species_23 = species_7

vPK

pyruvate kinase

species_4 + species_2 = species_1 + species_3

vPT

pyruvate transport

species_1 > species_26

vTPI

triosephosphate isomerase

species_17 = species_18

Parameters

Global parameters
vAKc
vAKg
vALD
vANTI
vAU
vENO
vGAPDH
vGK
vGPDH
vGPO
vGT
vGlyT
vHK
vPFK
vPGI
vPGK
vPGM
vPGT
vPK
vPT
vTPI

Fixed species

Initial values

Functions and Rules

Events

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei.

  • Marie-Astrid Albert
  • Jurgen R Haanstra
  • Véronique Hannaert
  • Joris Van Roy
  • Fred R Opperdoes
  • Barbara M Bakker
  • Paul A M Michels
J. Biol. Chem. 2005; 280 (31): 28306-28315
Abstract
A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was developed previously on the basis of all available enzyme kinetic data (Bakker, B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol. Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular metabolite concentrations as measured in non-growing trypanosomes and the major contribution to the flux control exerted by the plasma membrane glucose transporter. Surprisingly, a large overcapacity was predicted for hexokinase (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our further analysis of the control of glycolytic flux in bloodstream form T. brucei. First, the model was optimized and extended with recent information about the kinetics of enzymes and their activities as measured in lysates of in vitro cultured growing trypanosomes. Second, the concentrations of five glycolytic enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes were changed by RNA interference. The effects of the knockdown of these enzymes on the growth, activities, and levels of various enzymes and glycolytic flux were studied and compared with model predictions. Data thus obtained support the conclusion from the in silico analysis that HXK, PFK, and PYK are in excess, albeit less than predicted. Interestingly, depletion of PFK and enolase had an effect on the activity (but not, or to a lesser extent, expression) of some other glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like organelles harboring the first seven enzymes of the glycolytic pathway of trypanosomes) and in the cytosol were affected. These data suggest the existence of novel regulatory mechanisms operating in trypanosome glycolysis.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000211) Biomodels notes: The model reproduces Figure 5 of the original paper. The model was simulated using Copasi v.4.4.27.