JWS Online

bulik1

Detail

Download

Reactions

v0

MGlcout = MGlcin

v1

MATP + MGlcin = MGlc6P

v10

M2PGri = M3PGri

v11

M2PGri = MPEP

v12

MPEP = MPyr + MATP

v13

MPyr = MNAD + MLac

v14

MPyr = MNADP + MLac

v15

MATP = MPi

v16

∅ = MATP + MAMP

v17

MGlc6P + MNADP = M6PGlcA

v18

MNADP + M6PGlcA = MRul5P

v19

∅ = {2.0}MGSH + MNADP

v2

MFru6P = MGlc6P

v20

{2.0}MGSH = ∅

v21

MRul5P = MXul5P

v22

MRul5P = MRib5P

v23

MXul5P + MRib5P = MSed7P + MGraP

v24

MSed7P + MGraP = MFru6P + ME4P

v25

MATP + MRib5P = MAMP

v26

MXul5P + ME4P = MFru6P + MGraP

v27

MPiex = MPi

v28

MLacex = MLac

v29

MPyrex = MPyr

v3

MATP + MFru6P = MFru16P2

v4

MGraP + MDHAP = MFru16P2

v5

MGraP = MDHAP

v6

M13P2Gri = MNAD + MGraP + MPi

v7

M13P2Gri = MATP + M3PGri

v8

M13P2Gri = M23P2Gri

v9

M23P2Gri = M3PGri + MPi

Parameters

Global parameters

PAtot*

PGStotal*

PInhibv1*

PK13P2Gv6*

PK13P2Gv7*

PK1v23*

PK1v24*

PK1v26*

PK23P2Gv1*

PK2PGv10*

PK2PGv11*

PK2v23*

PK2v24*

PK2v26*

PK3PGv10*

PK3PGv7*

PK3v23*

PK3v24*

PK3v26*

PK4v23*

PK4v24*

PK4v26*

PK5v23*

PK5v24*

PK5v26*

PK6PG1v18*

PK6PG2v18*

PK6v23*

PK6v24*

PK6v26*

PK7v23*

PK7v24*

PK7v26*

PKADPv16*

PKAMPv16*

PKAMPv3*

PKATPv12*

PKATPv16*

PKATPv17*

PKATPv18*

PKATPv25*

PKATPv3*

PKDHAPv4*

PKDHAPv5*

PKFru16P2v12*

PKFru16P2v4*

PKFru6Pv2*

PKFru6Pv3*

PKG6Pv17*

PKGSHv19*

PKGSSGv19*

PKGlc6Pv1*

PKGlc6Pv2*

PKGraPv4*

PKGraPv5*

PKGraPv6*

PKMGlcv1*

PKMg23P2Gv1*

PKMgADPv12*

PKMgADPv7*

PKMgATPMgv1*

PKMgATPv1*

PKMgATPv3*

PKMgATPv7*

PKMgv1*

PKMgv3*

PKMinv0*

PKMoutv0*

PKNADHv6*

PKNADPHv17*

PKNADPHv18*

PKNADPHv19*

PKNADPv17*

PKNADPv18*

PKNADPv19*

PKNADv6*

PKPEPv11*

PKPEPv12*

PKPGA23v17*

PKPGA23v18*

PKPv6*

PKR5Pv22*

PKR5Pv25*

PKRu5Pv21*

PKRu5Pv22*

PKX5Pv21*

PKd1*

PKd2*

PKd23P2G*

PKd3*

PKd4*

PKdADP*

PKdAMP*

PKdATP*

PKequv15*

PKequv20*

PKeqv0*

PKeqv1*

PKeqv10*

PKeqv11*

PKeqv12*

PKeqv13*

PKeqv14*

PKeqv16*

PKeqv17*

PKeqv18*

PKeqv19*

PKeqv2*

PKeqv21*

PKeqv22*

PKeqv23*

PKeqv24*

PKeqv25*

PKeqv26*

PKeqv27*

PKeqv28*

PKeqv29*

PKeqv3*

PKeqv4*

PKeqv5*

PKeqv6*

PKeqv7*

PKeqv8*

PKeqv9*

PKiGraPv4*

PKiiGraPv4*

PKv20*

PL0v12*

PL0v3*

PMgtot*

PNADPtot*

PNADtot*

PPRPP*

PVmax1v1*

PVmax2v1*

PVmaxATPase*

PVmaxv0*

PVmaxv10*

PVmaxv11*

PVmaxv12*

PVmaxv13*

PVmaxv16*

PVmaxv17*

PVmaxv18*

PVmaxv19*

PVmaxv2*

PVmaxv21*

PVmaxv22*

PVmaxv23*

PVmaxv24*

PVmaxv25*

PVmaxv26*

PVmaxv27*

PVmaxv28*

PVmaxv29*

PVmaxv3*

PVmaxv4*

PVmaxv5*

PVmaxv6*

PVmaxv7*

PVmaxv9*

Palfav0*

PkATPasev15*

PkDPGMv8*

PkLDHv14*

Pprotein1*

Pprotein2*

Pr*

cell*

extracellular*

default*

Initial values

M13P2Gri*

M23P2Gri*

M2PGri*

M3PGri*

M6PGlcA*

MAMP*

MATP*

MDHAP*

ME4P*

MFru16P2*

MFru6P*

MGSH*

MGlc6P*

MGlcin*

MGraP*

MLac*

MNAD*

MNADP*

MPEP*

MPi*

MPyr*

MRib5P*

MRul5P*

MSed7P*

MXul5P*

PMgf*

PNADPHf*

PNADPf*

Functions and Rules

Assignment rules

MGSSG = (PGStotal - MGSH) / 2.0

PMgAMP = MAMP * PMgf / (PKdAMP + PMgf)

PATPf = MATP - PMgATP

PMgADP = MADP * PMgf / (PKdADP + PMgf)

PMgATP = MATP * PMgf / (PKdATP + PMgf)

MADP = PAtot - MATP - MAMP

PADPf = MADP - PMgADP

PAMPf = MAMP - PMgAMP

PNADH = PNADtot - MNAD

MNADPH = PNADPtot - MNADP

PMg23P2Gri = M23P2Gri * PMgf / (PKd23P2G + PMgf)

Pprotein1f = Pprotein1 / (1.0 + PNADPf / PKd1 + PNADPHf / PKd3)

Pprotein2f = Pprotein2 / (1.0 + PNADPf / PKd2 + PNADPHf / PKd4)

P23P2Grif = M23P2Gri - PMg23P2Gri

Function definitions

Constraints

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

Snap to grid*

Show wireframe*

Show modifiers*

Show compartments*

Gravity*

Repulsion*

Pool threshold*

Species:

Reactions:

Middle-click: pin/unpin nodes
Shift-click: pool/unpool species
Right-click: context menu

Apply alternate model layout to overlapping elements in current model:

Model schema*

Start time*

End time*

log scales

y-axis min/max

x-axis min/max

Species

Rates

Assignment rules

Parameter*

Start*

End*

Steps*

Species

Rates

Assignment rules

Kinetic hybrid models composed of mechanistic and simplified enzymatic rate laws--a promising method for speeding up the kinetic modelling of complex metabolic networks.

Sascha Bulik
Sergio Grimbs
Carola Huthmacher
Joachim Selbig
Hermann-Georg Holzhütter

FEBS J. 2009; 276 (2): 410-424

PubMed: 19137631
ISSN: 1742-4658
URL: http://ncbi.nlm.nih.gov/pubmed/19137631

Abstract

Kinetic modelling of complex metabolic networks - a central goal of computational systems biology - is currently hampered by the lack of reliable rate equations for the majority of the underlying biochemical reactions and membrane transporters. On the basis of biochemically substantiated evidence that metabolic control is exerted by a narrow set of key regulatory enzymes, we propose here a hybrid modelling approach in which only the central regulatory enzymes are described by detailed mechanistic rate equations, and the majority of enzymes are approximated by simplified(non mechanistic) rate equations (e.g. mass action, LinLog, Michaelis-Menten and power law) capturing only a few basic kinetic features and hence containing only a small number of parameters to be experimentally determined. To check the reliability of this approach, we have applied it to two different metabolic networks, the energy and redox metabolism of red blood cells, and the purine metabolism of hepatocytes, using in both cases available comprehensive mechanistic models as reference standards. Identification of the central regulatory enzymes was performed by employing only information on network topology and the metabolic data for a single reference state of the network [Grimbs S, Selbig J, Bulik S, Holzhutter HG & Steuer R (2007) Mol Syst Biol 3, 146, doi:10.1038/msb4100186].Calculations of stationary and temporary states under various physiological challenges demonstrate the good performance of the hybrid models. We propose the hybrid modelling approach as a means to speed up the development of reliable kinetic models for complex metabolic networks.

No additional notes are available for this model.

JWS Online documentation

M13P2Gri
M23P2Gri
M2PGri
M3PGri
M6PGlcA
MAMP
MATP
MDHAP
ME4P
MFru16P2
MFru6P
MGSH
MGlc6P
MGlcin
MGraP
MLac
MNAD
MNADP
MPEP
MPi
MPyr
MRib5P
MRul5P
MSed7P
MXul5P
PMgf
PNADPHf (PNADPHf)
PNADPf

v0
v1 (v1)
v10
v11
v12 (v12)
v13
v14 (v14)
v15
v16
v17 (v17)
v18 (v18)
v19 (v19)
v2
v20
v21
v22
v23
v24
v25
v26
v27
v28
v29
v3 (v3)
v4
v5
v6
v7
v8
v9