| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | I1 | PP1_PSD
Pathway No. 262 | Network | 4 | 0.01 | No | - |
| | I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM. |
| 2 | I1* | PP1_PSD
Pathway No. 262 | Network | 0 | 0.01 | No | - |
| | Dephosph is mainly by PP2B |
| 3 | PP1-I1* | PP1_PSD
Pathway No. 262 | Network | 0 | 0.01 | No | - |
| 4 | PP1-I1 | PP1_PSD
Pathway No. 262 | Network | 0 | 0.01 | No | - |
| 5 | CaNAB | PP2B
Pathway No. 261 | Network | 1 | 0.09 | No | - |
| | We assume that the A and B subunits of PP2B are always bound under physiol conditions. Up to 1% of brain protein = 25 uM. I need to work out how it is distributed between cytosolic and particulate fractions. Tallant and Cheung '83 Biochem 22 3630-3635 have conc in many species, average for mammalian brain is around 1 uM. |
| 6 | CaNAB-Ca2 | PP2B
Pathway No. 261 | Network | 0 | 0.09 | No | - |
| 7 | I1 | PP1
Pathway No. 260 | Network | 1.8 | 0.09 | No | - |
| | I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM. |
| 8 | I1* | PP1
Pathway No. 260 | Network | 0 | 0.09 | No | - |
| | Dephosph is mainly by PP2B |
| 9 | PP1-I1* | PP1
Pathway No. 260 | Network | 0 | 0.09 | No | - |
| 10 | PP1-I1 | PP1
Pathway No. 260 | Network | 0 | 0.09 | No | - |
| 11 | CaM | CaM
Pathway No. 259 | Network | 26.3333 | 0.09 | No | - |
| | There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels. |
| 12 | CaM-PSD | CaM
Pathway No. 259 | Network | 26.3333 | 0.01 | No | - |
| | There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels. |
| 13 | CaMKII | CaMKII
Pathway No. 258 | Network | 20 | 0.09 | No | - |
| | Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around 2.5% of protein in spine as a whole. This level is so high it is unlikely to matter much if we are off a bit. |
| 14 | CaMKII-CaM | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | - |
| 15 | CaMKII-thr286*-C
aM | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | - |
| | From Hanson and Schulman, the thr286 is responsible for autonomous activation of CaMKII. |
| 16 | CaMKII*** | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | - |
| | From Hanson and Schulman, the CaMKII does a lot of autophosphorylation just after the CaM is released. This prevents further CaM binding and renders the enzyme quite independent of Ca. |
| 17 | CaMKII-thr286 | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | - |
| | I am not sure if we need to endow this one with a lot of enzs. It is likely to be a short-lived intermediate, since it will be phosphorylated further as soon as the CAM falls off. |
| 18 | CaMK-thr305 | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | - |
| | This forms due to basal autophosphorylation, but I think it has to be considered as a pathway even if some CaM is floating around. In either case it will tend to block further binding of CaM, and will not display any enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992 |
| 19 | tot_CaM_CaMKII | CaMKII
Pathway No. 258 | Network | 0 | 0.09 | No | CaMKII-CaM
CaMKII-thr286*-C
aM
|
| 20 | tot_autonomous_
CaMKII | CaMKII
Pathway No. 258 | Network | 2 | 0.09 | No | CaMKII-thr286
CaMKII***
basal_CaMKII_
cyt
|
and 
color.