| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | APC | PLA2
Pathway No. 72 | Network | 30 | 1000 | Yes | - |
| | arachodonylphosphatidylcholine is the favoured substrate from Wijkander and Sundler, JBC 202 pp 873-880, 1991. Their assay used 30 uM substrate, which is what the kinetics in this model are based on. For the later model we should locate a more realistic value for APC. For now it is treated as a buffered metabolite. |
| 2 | temp-PIP2 | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 2.5 | 1000 | Yes | - | |
| | This is a steady PIP2 input to PLA2. The sensitivity of PLA2 to PIP2 discussed below does not match with the reported free levels which are used by the phosphlipase Cs. My understanding is that there may be different pools of PIP2 available for stimulating PLA2 as opposed to being substrates for PLCs. For that reason I have given this PIP2 pool a separate identity. As it is a steady input this is not a problem in this model. Majerus et al Cell 37:701-703 report a brain concentration of 0.1 - 0.2 mole % Majerus et al Science 234:1519-1526 report a huge range of concentrations: from 1 to 10% of PI content, which is in turn 2-8% of cell lipid. This gives 2e-4 to 8e-3 of cell lipid. In concentrations in total volume of cell (a somewhat strange number given the compartmental considerations) this comes to anywhere from 4 uM to 200 uM. PLA2 is stim 7x by PIP2 (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, so I'll use a value at the lower end of the scale for basal PIP2. |
| 3 | Inositol | PLCbeta
Pathway No. 73 | Network | 0 | 1000 | Yes | - |
| | Very simplified degradation product of IP3. There is a very interesting and complex phosphorylation/dephosphorylation cascade on the inositol phosphates, but that is outside the scope of this model. |
| 4 | PC | PLCbeta
Pathway No. 73 | Network | 0 | 0.0016667 | Yes | - |
| | Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987) |
| 5 | mGluRAntag | Gq
Pathway No. 74 | Network | 0 | 1000 | Yes | - |
| | I implement this as acting only on the Rec-Gq complex, based on a more complete model PLC_Gq48.g which showed that the binding to the receptor alone contributed only a small amount. |
| 6 | EGF | EGFR
Pathway No. 77 | Network | 0 | 1000 | Yes | - |
| | Epidermal growth factor. |
| 7 | total-CaMKII | CaMKII
Pathway No. 80 | Network | 70 | 1000 | Yes | - |
| | This pool is purely here to provide a single, fixed number, which is the total amount of CaMKII. This is used by the autophosphorylation steps to scale down the rates so that the autophosphorylation reactions are independent of CaMKII levels. |
| 8 | ATP | AC
Pathway No. 85 | Network | 5000 | 1000 | Yes | - |
| | ATP is present in all cells between 2 and 10 mM. See Lehninger. |
| 9 | AMP | AC
Pathway No. 85 | Network | 10 | 0.0016667 | Yes | - |
| | AMP is a tightly regulated metabolite, so here we simply buffer it to its resting value. The value doesn't really matter to any of the calculations since it acts like a one-way sink. |
| 10 | Ca-leak-to-cytop
lasm | CaRegulation
Pathway No. 86 | Network | 0.024 | 1000 | Yes | - |
| | This pool represents the channels which leak Ca into the cytoplasm. It is a probably a composite of various channels depending on cell type. Membrane potential will obviously affect the leak amount, but that is not considered. The amounts and total flux are constrained by the need to balance the Ca flux and keep basal Ca levels around 80 nM. |
| 11 | Ca-ext | CaRegulation
Pathway No. 86 | Network | 4000 | 100000 | Yes | - |
| | Extracell Ca conc = 4 mM Extracell vol assumed 100 X cell vol It is kept buffered anyway for the puroposes of the model, so the concentration won't change. |
| 12 | PIP2 | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 10 | 1000 | Yes | - | |
| | PIP2 is a bit troublesome in this model. Its level is well below what it should be based on more recent data. This value is kept in this model to correspond to the Km used in the enzymes. A scale factor of 5-10 in both terms would cancel out but improve the parameter estimate. |
| 13 | PKC-Ca | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This intermediate is strongly indicated by the synergistic activation of PKC by combinations of DAG and Ca, as well as AA and Ca. PKC by definition also has a direct Ca-activation, to which this also contributes. |
| 14 | PKC-DAG-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Membrane translocated form of PKC-DAG-AA complex. |
| 15 | PKC-Ca-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Membrane bound and active complex of PKC, Ca and AA. |
| 16 | PKC-Ca-memb* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the direct Ca-stimulated activity of PKC. |
| 17 | PKC-DAG-memb* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Active, membrane attached form of Ca.DAG.PKC complex. |
| 18 | PKC-basal* | PKC
Pathway No. 71 | Network | 0.02 | 1000 | No | - |
| | This is the basal PKC activity which contributes about 2% to the maximum. |
| 19 | PKC-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the membrane-bound and active form of the PKC-AA complex. |
| 20 | PKC-Ca-DAG | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the active PKC form involving Ca and DAG. It has to translocate to the membrane. |
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color.