| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | Ca-sequester | CaRegulation
Pathway No. 86 | Network | 6.3328 | 160 | No | - |
| | This is the sequestered Calcium pool. The vol is 0.16 * the vol of the cell as a whole. This pool should really equilibrate with a highly buffered pool of Calcium, but that is not present in this version of the model. |
| 2 | CaTransp-2Ca | CaRegulation
Pathway No. 86 | Network | 0 | 1000 | No | - |
| | This is equivalent to the enzyme-substrate complex. 2 Ca are bound to the transporter. The ATP is ignored. |
| 3 | CaTransp | CaRegulation
Pathway No. 86 | Network | 0.24 | 1000 | No | - |
| | The calcium transporter levels are constrained by the resting levels of Ca in the cell. The rate of Ca sequestration depends on the amount of this pool. |
| 4 | IP3R | CaRegulation
Pathway No. 86 | Network | 0.0166 | 1000 | No | - |
| | The number of the IP3Rs in the cell is present only implicitly in the model, and is lumped in with the total permeability of the IP3R pool. The latter term is constrained by the height of the Ca transient. |
| 5 | IP3R* | CaRegulation
Pathway No. 86 | Network | 0 | 1000 | No | - |
| | This is the ligand-bound form of the IP3 receptor. |
| 6 | CaEPump | CaRegulation
Pathway No. 86 | Network | 0.005 | 1000 | No | - |
| | The calcium electrogenic pump. See McBurney and Neering 1987 TINS 10(4):164-169 We treat the pump as a simple Michaelis-Menten enzyme. Levels are constrained tightly by the need to keep resting Ca levels at about 80 nM. |
| 7 | Ca-leak-from-ext
racell | CaRegulation
Pathway No. 86 | Network | 0.0008 | 1000 | No | - |
| | This represents the pool of Ca leak channels. The concentration gradient is so large that this pool only needs a small number of molecules. For an equilibrium at 0.1 uM we need flow of 36e3/sec. With a permeability of 0.01 and a concentration gradient of 4mM->0.1 uM (4e4) we get flux = N * perm * grad => N = 36e3 / (1e-2 * 4e3) = 900 if flux = 20e3, N =500, which is what we use. This works out to a concentration of 0.83 nM. |
| 8 | capacitive_Ca_
entry* | CaRegulation
Pathway No. 86 | Network | 0.01 | 1000 | No | - |
| | This mechanism has taken a while to be more tightly confirmed as probably being the TRP channel. In this model the channel is implemented to match experimental observations about capacitive Ca entry. Levels are set by two constraints: the resting Ca levels, and the height of the response to IP3. |
| 9 | inact_cap_entry | CaRegulation
Pathway No. 86 | Network | 0 | 1000 | No | - |
| | This represents the portion of the capacitive-Ca entry channel which is blocked when there is lots of Ca sequestered in the stores. |
| 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 | AC1-CaM | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This state of AC1 is bound to Calmodulin and therefore activated. Gs stimulates it but betagamma inhibits. |
| 13 | AC1 | AC
Pathway No. 85 | Network | 0.02 | 1000 | No | - |
| | AC concentrations are tricky due to poor antibodies. I refer to an estimate from Jacobowitz, PhD Thesis, Mount Sinai School of Medicine around Pg 149 which estimates cyclase as 1/12600 of membrane protein. This gives a whole-cell conc of about 33 nM using assumptions of 2% of cell mass being membrane protein. Defer et al 2000 Am J Physiol Renal Physiol 279:F400-F416 in a good review put AC1 and AC8 (which has similar properties) as among the highly expressed form of brain cyclase. We therefore estimate its levels as a good fraction of the 33 nM, at 20 nM. |
| 14 | AC2* | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This is the phosphorylation-activated form of AC2. |
| 15 | AC2-Gs | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This is the generic Gs-Stimulated form of AC2 |
| 16 | AC2 | AC
Pathway No. 85 | Network | 0.015 | 1000 | No | - |
| | AC concentrations are tricky due to poor antibodies. I refer to an estimate from Jacobowitz, PhD Thesis, Mount Sinai School of Medicine around Pg 149 which estimates cyclase as 1/12600 of membrane protein. This gives a whole-cell conc of about 33 nM using assumptions of 2% of cell mass being membrane protein. Defer et al 2000 Am J Physiol Renal Physiol 279:F400-F416 in a good review put AC2 among the highly expressed form of brain cyclase. We therefore estimate its levels as a good fraction of the 33 nM, at 15 nM. This actually adds up to a little more than 33, but it is well within error estimates. |
| 17 | AC1-Gs | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This is the generic Gs-Stimulated state of AC1. Note that the enzyme is normally saturated, so all reactions involving AC1-Gs actually relate to the enzyme-substrate complex. |
| 18 | AC2*-Gs | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This is the form activated synergistically by phosphorylation as well as Gs binding. |
| 19 | cAMP-PDE | AC
Pathway No. 85 | Network | 0.45 | 1000 | No | - |
| | The levels of the PDE are not known at this time. However, enough kinetic info and info about steady-state levels of cAMP etc are around to make it possible to estimate this. |
| 20 | cAMP-PDE* | AC
Pathway No. 85 | Network | 0 | 1000 | No | - |
| | This form has about 2X activity as plain PDE. See Sette et al JBC 269:28 18271-18274 1994. |
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