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Reaction List for pathway PLA2 (Pathway Number 36) |
| Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reactions is not considered. |
| Name | Kf | Kb | Kd | tau | Substrate | Product | |
| 1 | DAG-Ca-PLA2-act | 0.003 (uM^-1 s^-1) | 4 (s^-1) | Kd(bf) = 1333.3333(uM) | - | DAG PLA2-Ca* | DAG-Ca-PLA2* |
| Synergistic activation of PLA2 by Ca and DAG. Based on Leslie and Channon 1990 BBA 1045:261 The Kd is rather large and may reflect the complications in measuring DAG. For this model it is not critical since DAG is held fixed. | |||||||
| 2 | Degrade-AA | 0.4 (s^-1) | 0 (s^-1) | - | - | AA | APC |
| Degradation pathway for AA. APC is a convenient buffered pool to dump it back into, though the actual metabolism is probably far more complex. For the purposes of the full model we use a rate of degradation of 0.4/sec to give a dynamic range of AA comparable to what is seen experimentally. Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261 | |||||||
| 3 | dephosphorylate- PLA2* | 0.17 (s^-1) | 0 (s^-1) | - | - | PLA2* | PLA2-cytosolic |
| Dephosphorylation reaction to balance MAPK phosphorylation of PLA2. This is probably mediated by PP2A. Rates determined to keep the balance of phosphorylated and non-phosphorylated PLA2 reasonable. The constraining factor is the fold activation of PLA2 by MAPK. | |||||||
| 4 | PIP2-Ca-PLA2-act | 0.012 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 8.3333(uM) | - | temp-PIP2 PLA2-Ca* | PIP2-Ca-PLA2* |
| Synergistic activation of PLA2 by Ca and PIP2. Again from Leslie and Channon 1990 BBA 1045:261 | |||||||
| 5 | PIP2-PLA2-act | 0.0012 (uM^-1 s^-1) | 0.5 (s^-1) | Kd(bf) = 416.6667(uM) | - | temp-PIP2 PLA2-cytosolic | PIP2-PLA2* |
| Activation of PLA2 by PIP2. From Leslie and Channon 1990 BBA 1045:261 the stimulation of PLA2 activity by high PIP2 is 7x. In this model we don't really expect any PIP2 stimulus. | |||||||
| 6 | PLA2*-Ca-act | 6 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.0167(uM) | - | PLA2* Ca | PLA2*-Ca |
| Nemenoff et al 1993 JBC 268:1960 report a 2X to 4x activation of PLA2 by MAPK, which seems dependent on Ca as well. This reaction represents this activation. Rates are scaled to give appropriate fold activation. | |||||||
| 7 | PLA2-Ca-act | 1 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.1(uM) | - | PLA2-cytosolic Ca | PLA2-Ca* |
| Direct activation of PLA2 by Ca. From Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267. | |||||||
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