JWS Online

maher1

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Reactions

v_1

{148445.0}ornmat + {148445.0}cp = {148445.0}pi + {148445.0}citmat

v_10

{40395.6}asR = {40395.6}fum + {40395.6}argR

v_11

{40395.6}arg = {40395.6}ure + {40395.6}orn

v_12

{40395.6}argR = {40395.6}ureR + {40395.6}orn

v_13

{40395.6}argQ = {40395.6}ure + {40395.6}orn

v_14

{509.861}argE = {509.861}ureE + {509.861}ornE

v_15

{509.861}argRE = {509.861}ureRE + {509.861}ornE

v_16

{509.861}argQE = {509.861}ureE + {509.861}ornE

v_17

{40395.6}orn = {244266.0}ornims

v_18

{244266.0}ornims = {148445.0}ornmat

v_19

{509.861}cppool = {509.861}cpeE

v_2

{148445.0}ornmat + {148445.0}cpR = {148445.0}pi + {148445.0}citmatR

v_20

{40395.6}cpe = {244266.0}cpims

v_21

{244266.0}cpims = {148445.0}cp

v_22

{40395.6}cpeR = {244266.0}cpimsR

v_23

{244266.0}cpimsR = {148445.0}cpR

v_24

{40395.6}atppool = {40395.6}atp

v_25

{40395.6}asppool = {40395.6}asp

v_26

{40395.6}ppi = XX

v_27

{40395.6}fum = XX

v_28

{148445.0}pi = XX

v_29

{40395.6}amp = XX

v_3

{148445.0}citmat = {244266.0}citims

v_30

{40395.6}ure = XX

v_31

{40395.6}ureR = XX

v_32

{40395.6}cit = {509.861}citE

v_33

{40395.6}citR = {509.861}citRE

v_34

{40395.6}atp = {509.861}atpE

v_35

{40395.6}asp = {509.861}aspE

v_36

{40395.6}amp = {509.861}ampE

v_37

{40395.6}ppi = {509.861}ppiE

v_38

{40395.6}as = {509.861}asE

v_39

{40395.6}asR = {509.861}asRE

v_4

{148445.0}citmatR = {244266.0}citimsR

v_40

{40395.6}fum = {509.861}fumE

v_41

{40395.6}argQ = {509.861}argQE

v_42

{40395.6}arg = {509.861}argE

v_43

{40395.6}argR = {509.861}argRE

v_44

{40395.6}ure = {509.861}ureE

v_45

{40395.6}ureR = {509.861}ureRE

v_46

{40395.6}orn = {509.861}ornE

v_47

{40395.6}cpe = {509.861}cpeE

v_48

{40395.6}cpeR = {509.861}cpeRE

v_5

{244266.0}citims = {40395.6}cit

v_6

{244266.0}citimsR = {40395.6}citR

v_7

{40395.6}cit + {40395.6}atp + {40395.6}asp = {40395.6}ppi + {40395.6}as + {40395.6}amp

v_8

{40395.6}citR + {40395.6}atp + {40395.6}asp = {40395.6}ppi + {40395.6}asR + {40395.6}amp

v_9

{40395.6}as = {40395.6}fum + {40395.6}arg

Parameters

Global parameters

Kiarg*

ampfinal*

argfac*

aslAdj*

assAdj*

cellV*

cytV*

e10*

e20*

e30*

e40*

e40E*

eV*

fm*

fmE*

fumfinal*

imsV*

k10e2*

k11e2*

k12e2*

k1e1*

k1e2*

k1e3*

k1e4*

k2e1*

k2e2*

k2e3*

k2e4*

k3e1*

k3e2*

k3e3*

k3e4*

k4e1*

k4e2*

k4e3*

k4e4*

k5e1*

k5e2*

k5e3*

k5e4*

k6e1*

k6e2*

k6e3*

k7e1*

k7e2*

k8e1*

k8e2*

k9e2*

kamp*

kampCE*

kampCEREV*

kargCE*

kargCEREV*

kargQCE*

kargQCEREV*

kargRCE*

kargRCEREV*

kasCE*

kasCEREV*

kasRCE*

kasRCEREV*

kasp*

kaspCE*

kaspCEREV*

katp*

katpCE*

katpCEREV*

kcitCE*

kcitCEREV*

kcitRCE*

kcitRCEREV*

kcitci*

kcitic*

kcitim*

kcitmi*

kcp*

kcpeCE*

kcpeCEREV*

kcpeRCE*

kcpeRCEREV*

kcpei*

kcpie*

kcpim*

kcpmi*

kfum*

kfumCE*

kfumCEREV*

kornCE*

kornCEREV*

kornci*

kornic*

kornim*

kornmi*

kpi*

kppi*

kppiCE*

kppiCEREV*

kure*

kureCE*

kureCEREV*

kureRCE*

kureRCEREV*

matV*

mitoV*

nucV*

otcAdj*

pifinal*

ppifinal*

sampleV*

steadyStateUreaProdn*

urefinal*

default*

Initial values

amp*

ampE*

arg*

argE*

argQ*

argQE*

argR*

argRE*

as*

asE*

asR*

asRE*

asp*

aspE*

atp*

atpE*

cit*

citE*

citR*

citRE*

citims*

citimsR*

citmat*

citmatR*

cp*

cpR*

cpe*

cpeE*

cpeR*

cpeRE*

cpims*

cpimsR*

fum*

fumE*

orn*

ornE*

ornims*

ornmat*

pi*

ppi*

ppiE*

ure*

ureE*

ureR*

ureRE*

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

Mathematical modelling of the urea cycle. A numerical investigation into substrate channelling.

Anthony D Maher
Philip W Kuchel
Fernando Ortega
Pedro de Atauri
Josep Centelles
Marta Cascante

Eur. J. Biochem. 2003; 270 (19): 3953-3961

PubMed: 14511377
ISSN: 0014-2956
URL: https://ncbi.nlm.nih.gov/pubmed/14511377

Abstract

Metabolite channelling, the process in which consecutive enzymes have confined substrate transfer in metabolic pathways, has been proposed as a biochemical mechanism that has evolved because it enhances catalytic rates and protects unstable intermediates. Results from experiments on the synthesis of radioactive urea [Cheung, C., Cohen, N.S. & Raijman, L (1989) J. Biol. Chem.264, 4038-4044] have been interpreted as implying channelling of arginine between argininosuccinate lyase and arginase in permeabilized hepatocytes. To investigate this interpretation further, a mathematical model of the urea cycle was written, using Mathematica it simulates time courses of the reactions. The model includes all relevant intermediates, peripheral metabolites, and subcellular compartmentalization. Analysis of the output from the simulations supports the argument for a high degree of, but not absolute, channelling and offers insights for future experiments that could shed more light on the quantitative aspects of this phenomenon in the urea cycle and other pathways.

The model reproduces Fig 2 of the paper.

JWS Online documentation

amp
ampE
arg
argE
argQ (argQ)
argQE (argQE)
argR
argRE
as
asE
asR
asRE
asp
aspE
atp
atpE
cit
citE
citR
citRE
citims
citimsR
citmat
citmatR
cp
cpR
cpe
cpeE
cpeR
cpeRE
cpims
cpimsR
fum
fumE
orn
ornE
ornims
ornmat
pi
ppi
ppiE
ure
ureE
ureR
ureRE

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v_11 (v_11)
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v_16 (v_16)
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v_30 (v_30)
v_31
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v_45 (v_45)
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