| Enzyme Molecule / Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents |
1 | PKC-active / PKC-act-raf
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 66.6667 | 4 | 4 | explicit E-S complex | Substrate craf-1
Product craf-1*
|
| Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC |
2 | PKC-active / PKC-inact-GAP
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 3.33333 | 4 | 4 | explicit E-S complex | Substrate GAP
Product GAP*
|
| Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review. |
3 | PKC-active / PKC-act-GEF
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 3.33333 | 4 | 4 | explicit E-S complex | Substrate inact-GEF
Product GEF*
|
| Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X |
4 | PKC-active / PKC-phosph-neuro granin
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 28.6275 | 0.58 | 4.03448 | explicit E-S complex | Substrate neurogranin
Product neurogranin*
|
| Rates from Huang et al ABB 305:2 570-580 1993 |
5 | PKC-active / PKC-phosph-ng-Ca M
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 28.5948 | 0.35 | 4 | explicit E-S complex | Substrate neurogranin-CaM
Product CaM neurogranin*
|
| Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993 |
6 | PKC-active / phosph-AC2
| MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 33.3333 | 4 | 4 | explicit E-S complex | Substrate AC2
Product AC2*
|
| Phorbol esters have little effect on AC1 or on the Gs-stimulation of AC2. So in this model we are only dealing with the increase in basal activation of AC2 induced by PKC k1 = 1.66e-6 k2 = 16 k3 =4 |