Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model is valid CellML and appears to match the published equations. However the model will not run in either COR or OpenCell.
Model Structure
ABSTRACT: In trypanosomes the first part of glycolysis takes place in specialized microbodies, the glycosomes. Most glycolytic enzymes of Trypanosoma brucei have been purified and characterized kinetically. In this paper a mathematical model of glycolysis in the bloodstream form of this organism is developed on the basis of all available kinetic data. The fluxes and the cytosolic metabolite concentrations as predicted by the model were in accordance with available data as measured in non-growing trypanosomes, both under aerobic and under anaerobic conditions. The model also reproduced the inhibition of anaerobic glycolysis by glycerol, although the amount of glycerol needed to inhibit glycolysis completely was lower than experimentally determined. At low extracellular glucose concentrations the intracellular glucose concentration remained very low, and only at 5 mM of extracellular glucose, free glucose started to accumulate intracellularly, in close agreement with experimental observations. This biphasic relation could be related to the large difference between the affinities of the glucose transporter and hexokinase for intracellular glucose. The calculated intraglycosomal metabolite concentrations demonstrated that enzymes that have been shown to be near-equilibrium in the cytosol must work far from equilibrium in the glycosome in order to maintain the high glycolytic flux in the latter.
The original paper reference is cited below:
Glycolysis in Bloodstream Form Trypanosoma brucei Can Be Understood in Terms of the Kinetics of the Glycolytic Enzyme, Barbara M. Bakker, Paul A. M. Michels, Fred R. Opperdoes, and Hans V. Westerhoff, 1997, The Journal of Biological Chemistry
, 272, 3207-3215. PubMed ID: 9013556
A reaction diagram of glycolysis
The stoichiometric scheme of the model of glycolysis in the bloodstream form of the parasite Trypanosoma brucei.
Glc_o
external glucose
Glc_i
cytosolic glucose
Glc_6_P_g
glycosomal glucose-6-phopshate
Fru_6_P_g
glycosomal fructose 6-phopshate
hexose_P_g
total concentration of glycosomal six carbon phosphates
Fru_1_6_BP_g
glycosomal fructose 1,6-bisphopshate
GA_3_P_g
glycosomal glyceraldehyde 3-phopshate
triose_P
total concentration of three carbon phopshates
one_three_BPGA_g
glycosomal 1,3-bisphosphoglycerate
three_PGA
3-phosphoglycerate
two_PGA_c
cytosolic 2-phosphoglycerate
N
the sum of 3-phosphoglycerate, 2-phosphoglycerate, and phosphoenolpyruvate
PEP_c
cytosolic phosphoenolpyruvate
PYR_c
cytosolic pyruvate
glycerol_g
glycosomal glycerol
DHAP
dihydroxyacetone phosphate
DHAP_c
cytosolic dihydroxyacetone phosphate
DHAP_g
glycosomal dihydroxyacetone phosphate
Gly_3_P
glyceraldehyde 3-phopshate
Gly_3_P_c
cytosolic glyceraldehyde 3-phopshate
Gly_3_P_g
glycosomal glyceraldehyde 3-phopshate
NAD_g
glycosomal nicotinamide adenine dinucleotide positive
NADH_g
glycosomal nicotinamide adenine dinucleotide
P_g
total concentration of glycosomal adenosine phosphates
P_c
total concentration of cytosolic adenosine phosphates
ATP_g
glycosomal adenosine triphosphate
ATP_c
cytosolic adenosine triphosphate
ADP_g
glycosomal adenosine diphosphate
ADP_c
cytosolic adenosine diphosphate
AMP_g
glycosomal adenosine monophosphate
AMP_c
cytosolic adenosine monophosphate
c.lloyd@auckland.ac.nz
The University of Auckland, Auckland Bioengineering Institute
2005-04-27
2003-04-09
Changed model structure to remove the model element from the CellML.
Hans
Westerhoff
V
This is the CellML description of Bakker et al's 1997 mathematical
model of glycolysis in the parasite Trypanosoma brucei.
Glycolysis in Bloodstream Form Trypanosoma brucei Can Be Understood in Terms of the Kinetics of the Glycolytic Enzymes
272
3207
3215
Added publication date information.
James
Lawson
Richard
Peter
Villiger
John
Fixed e-notation error
Updated curation status
1997-02-07
2002-08-01T00:00:00+00:00
Catherine
Lloyd
May
2009-05-05T11:37:58+12:00
The University of Auckland
Auckland Bioengineering Institute
Fred
Opperdoes
R
The Journal of Biological Chemistry
A model of glycolysis in the parasite Trypanosoma brucei.
keyword
metabolism
glycolysis
Trypanosoma brucei
Catherine Lloyd
Catherine
Lloyd
May
Modified names to conform with cellml 1.1 naming conventions
and modified comment brackets.
2003-09-01
Autumn
Cuellar
A
Barbara
Bakker
M
Paul
Michels
A
M
9013556