JWS Online

reed

reed

 Detail
 Download

Reactions

v_1

v_1

met = SAM

v_10

ccys = ext

v_11

v_11

ccys + cglut = cglc

v_12

cglc + cgly = cGSH

v_13

{2.0}cGSH = cGSSG

v_14

cGSSG = {2.0}cGSH

v_15

cGSSG = bGSSG

v_16

cGSSG = bGSSG

v_17

cGSH = ext

v_18

cGSH = bGSH

v_19

cGSH = bGSH

v_2

v_2

met = SAM

v_20

cGSSG = ext

v_21

bglut = cglut

v_22

bcys = ccys

v_23

bser = cser

v_24

bgly = cgly

v_25

{3.0}mgly = cgly

v_26

{3.0}mHCOOH = cHCOOH

v_27

{3.0}mser = cser

v_28

cser + cTHF = cCH2THF + cgly

v_29

cDHF = cTHF

v_3

SAM = SAH

v_30

cTHF + cHCOOH = c10fTHF

v_31

c10fTHF = cTHF

v_32

c10fTHF = aic + cTHF

v_33

c10fTHF + aic = cTHF

v_34

cTHF = cCH2THF

v_35

cCHTHF = c10fTHF

v_36

cCH2THF = cDHF

v_37

cCH2THF = cCHTHF

v_38

v_38

cCH2THF = c5mTHF

v_39

mTHF + mser = mgly + mCH2THF

v_4

v_4

SAM + cgly = SAH + msarc

v_40

mTHF + mHCOOH = m10fTHF

v_41

m10fTHF = mTHF

v_42

mCHTHF = m10fTHF

v_43

mCH2THF = mCHTHF

v_44

mTHF + mgly = mCH2THF

v_45

mTHF + msarc = mgly + mCH2THF

v_46

mTHF + dmg = msarc + mCH2THF

v_47

mTHF = mCH2THF

v_48

bmet = met

v_49

v_49

ext = bcys

v_5

SAH = hcy

v_50

v_50

ext = bglut

v_51

v_51

ext = bgly

v_52

cser = ext

v_53

cglut = ext

v_54

bGSH = bgly + bcys + bglut

v_55

bGSSG = {2.0}bgly + {2.0}bcys + {2.0}bglut

v_56

bgly = ext

v_57

bcys = ext

v_58

bglut = ext

v_59

bGSH = ext

v_6

v_6

hcy = met + dmg

v_60

bGSSG = ext

v_7

hcy + c5mTHF = met + cTHF

v_8

v_8

hcy + cser = cyt

v_9

cyt = ccys

Parameters

Global parameters

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.


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:

log scales

y-axis min/max

x-axis min/max

A mathematical model of glutathione metabolism.

  • Michael C Reed
  • Rachel L Thomas
  • Jovana Pavisic
  • S Jill James
  • Cornelia M Ulrich
  • H Frederik Nijhout
Theor Biol Med Model 2008; 5 : 8
Abstract
BACKGROUND: Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism.
APPROACH: We explore the properties of glutathione metabolism in the liver by experimenting with a mathematical model of one-carbon metabolism, the transsulfuration pathway, and glutathione synthesis, transport, and breakdown. The model is based on known properties of the enzymes and the regulation of those enzymes by oxidative stress. We explore the half-life of glutathione, the regulation of glutathione synthesis, and its sensitivity to fluctuations in amino acid input. We use the model to simulate the metabolic profiles previously observed in Down syndrome and autism and compare the model results to clinical data.
CONCLUSION: We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that overexpression of genes on chromosome 21 and an increase in oxidative stress can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased and the adenosine concentration is raised. Finally, we discuss how individual variation arises and its consequences for one-carbon and glutathione metabolism.

No additional notes are available for this model.