From: Computational modelling of the regulation of Insulin signalling by oxidative stress
Module | Reaction | Name | Parameter | Value | Order | Comments & Ref |
---|---|---|---|---|---|---|
All |  | Volume | extracellular | 8.3 × 10-12 l |  | 0.5 × cytoplasm |
 |  | Volume | cell surface | 6.4 × 10-14 l |  | assumes thickness of 20 nm |
 |  | Volume | cytoplasm | 1.65 × 10-11 l |  | typical of many cells |
 |  | Volume | nucleus | 5 × 10-13 l |  |  |
 |  | Volume | DNA-bound | 1 × 10-13 l |  |  |
Receptor binding | R1f |  | k1 | 2.0 × 10-5 | 2 | |
m8b2_recep.6mod | R1r | Â | kminus1 | 12072 | 1 | [36] |
 | R2 |  | k3 | 2500 | 1 | [36] |
 | R3f |  | k2 | 1.2 × 10-5 | 2 | [36] |
 | R3r |  | kminus2 | 9 × 104 | 1 | > > kminus1 |
 | R4 |  | kminus3 | 2 × 10-6 | 2 (cat) |  |
 | R5f |  | k4 | 0.0333 | 1 | forward/reverse ratio 10, much faster than [26] |
 | R5r |  | kminus4 | 0.3 | 1 | see R5f |
 | R6f |  | k4’ | 0.0021 | 1 | unchanged from [26] |
 | R6r |  | kminus4’ | 2.1 × 10-4 | 1 | [26] |
 | R7f |  | k4’ | 0.0021 | 1 | [26] |
 | R7r |  | kminus4’ | 2.1 × 10-4 | 1 | [26] |
 | R10 |  | k6 | 4.61 × 10-6 | 2 (cat) | [26] corrected for mol number of PTP1B |
 | R11 |  | k6 | 4.61 × 10-6 | 2 (cat) | see R10 |
IRS | R12f | Â | k7 | 5.8 | 2 (cat) | fitted to IRSYp |
m8b2_irs.6.mod | R12r |  | kminus7a | 8.75 × 10-5 | 2 (cat) | as R12f |
 | R12_a_f | IRS-SerP by PKC_P | kpsp2 | 2.2 × 10-4 | 2 | changed to simple MA; [27] used for fitting |
 | R12_a_r |  | kminus7b | 0.28 × 10-5 | 2 (cat) | as R12_a_f |
 | R12_b_(f,r) |  | as R12_a_(f,r) |  |  |  |
 | R13f |  | k8 | 2.6 × 10-6 | 2 | |
 | R13r |  | kminus8 | 1.55 | 1 | as R13f |
 | R50f | IRS basal synth | k_irs1_basal_syn | 260 | 0 | increased to keep IRS1 const |
 | R50r1 | IRS degrade | k_irs_basal_degr | 10-3 | 1 | Lifetime of ~2 days |
 | R50r2 | IRS-Yp degr | k_irs_basal_degr | 10-3 | 1 | as R50r2 |
 | R50r3 | IRS1-Sp degr | k_irs_polyserp_degr | 10-2 | 1 | 10 × faster than r50r2 [43] |
 | R51 | IRS-SerP by IKK_P | kcat51 | 0.87 |  | consistent with [43] and IKK/JNK activation |
 |  | IRS-SerP by IKK_P | Km51 | 100 |  | as above |
 | R52 | IRS-SerP by JNK_P | kcat52 | 6.95 |  | as R51 |
 |  | IRS-SerP by JNK_P | Km52 | 100 |  | as above |
Phosphatases | R30f | oxidation of PTP1B | k30f | 0.08 | 2 | |
m8b2_phosph.6.mod | R30r | reduction of PTP1B by GSH | k30r | 5 × 10-3 | 2 | |
 | R31f | oxidation of PTEN | k31f | 2.7 × 10-4 | 2 | slower than R30f |
 | R31r | reduction of PTEN by GSH | k31r | 2 × 10-3 | 2 | similar to R30r |
 | R34f | Activation of NOX | k34f | 2 × 10-5 | 2 | consistent with R35 |
 | R34r1 | NOX deactivation | k34r1 | 10-3 | 2 | consistent with R35 |
 | R34r2 | NOX inactivation(1) | k34r2 | 0.25 | 1 | consistent with R35 |
 | R34r3 | NOX deact- > inact | k34r3 | 10-3 | 2 | consistent with R35 |
 | R35f | ROS production by NOX | k35f | 450 | 1 | fitted to get desired ROS level (30/5) and PTP1B inhibition [18] |
 | R35r | ROS elimination by SOD2 | k35r | 0.12 | 2 | lifetime < 0.01 s |
 | R36f | ROS production by Mitoch | k36f | 180 | 1 |  |
 | R37f, R37r | ROS transport across plasma membrane | ros_perm | 7.8 × 108 (thousands cm-2min-1) | 1 | [35] |
 |  |  | membrane_area | 6.5 × 10-9 cm2 |  | from volume |
 |  |  | k_ros_perm | 4.8 thousands min-1 |  | product of above |
 | R38f | Glutathione oxidation | k38f | 0.05 | 2 | see R38f |
 | R38r | Glutathione reduction | k38r | 2 | 1 | (auto-reduction) |
Akt | R14f | PI(3,4,5)P3 generation, basal | k9_basal | 0.13145 | 1 | [26] |
m8b2_akt.6.mod | Â | By PI3K complex | k9 | 0.055 | 2 (cat) | derived from [26] |
 | R14r | PIP3 breakdown, basal | kminus9_basal | 2.7 | 1 | [26] |
 |  | by PTEN | kminus9 | 0.0014 | 2 (cat) |  |
 | R16f | Akt activation | k11 | 2.5 × 10-5 | 2 | modified mass action, effect similar to express in [26] |
 |  |  | pip3_basal | 200 | 2 (cat) | offset |
 | R16r | Akt deactivation by PP2A | kminus11 | 1.188 × 10-6 | 2 (cat) | [26] |
 | R17f | PKC activation | k12 | 3.5 × 10-5 | 2 (cat) | as R16f |
 | R17r | PKC deactivation | kminus12 | 1.25 × 10-6 | 2 (cat) | as R16r |
 | R16a | AS160 activation by AKT | kr16a | 3.33 × 10-4 | 2 (cat) | |
 | R16r | AS160 deactivation | kminusr16a | 1 × 10-6 | 2 (cat) | see R16a |
 | R20f | GLUT4 translocation to cell surface; basal | k13_basal | 0.015 | 1 | see R16a |
 |  | and by AS160 | k13 | 7.5 × 10-6 | 2 (cat) | see R16a |
 | R20r | GLUT4 translocation to cytoplasm | kminus13 | 0.167 | 1 | see R16a |
JNK | R32f | DUSP oxidation | k32f | 6 × 10-4 | 2 (cat) | |
m8b2_jnk.6.mod | R32r | DUSP reduction by GSH | k32r | 4 × 10-4 | 2 (cat) | as R32f |
 | R42f | JNK activation by ROS | k42fa | 2.5 × 10-4 | 2 (cat) | as R32f |
 | R42r | JNK deactivation by DUSP | k42r | 0.5 × 10-6 | 2 (cat) | as R32f |
 | R43f | IKK activation by ROS | k43f | 0.5 × 10-4 | 2 (cat) | as R32f |
 | R43r | IKK deactivation | k43r | 0.5 × 10-6 | 2 (cat) | as R32f |