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Reaction List for pathway PKA (Pathway Number 84) |
| 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 | cAMP-bind-site-A 1 | 75 (uM^-1 s^-1) | 110 (s^-1) | Kd(bf) = 1.4667(uM) | - | R2C2-cAMP2 cAMP | R2C2-cAMP3 |
| This site has a higher Kd for cAMP. See Ogreid and Doskeland 1982 FEBS Lett 150:1 161-166 | |||||||
| 2 | cAMP-bind-site-A 2 | 75 (uM^-1 s^-1) | 32.5 (s^-1) | Kd(bf) = 0.4333(uM) | - | cAMP R2C2-cAMP3 | R2C2-cAMP4 |
| Cooperativity kicks in, now we have a low Kd for cAMP. | |||||||
| 3 | cAMP-bind-site-B 1 | 54 (uM^-1 s^-1) | 33 (s^-1) | Kd(bf) = 0.6111(uM) | - | R2C2 cAMP | R2C2-cAMP |
| Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Smith et al PNAS USA 78:3 1591-1595 1981 say that Ka1 is 2.1e7/M which gives a Kd of 47 nM, Kan = 5e8/M or Kd of 2nM. I prefer numbers from Ogreid and Doskeland Febs Lett 129:2 287-292 1981. Their conditions are more physiological. They have figs suggesting time course of complete assoc is < 1 min. | |||||||
| 4 | cAMP-bind-site-B 2 | 54 (uM^-1 s^-1) | 33 (s^-1) | Kd(bf) = 0.6111(uM) | - | R2C2-cAMP cAMP | R2C2-cAMP2 |
| For now let us set this to the same Km (1e-7M) as site B1. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 | |||||||
| 5 | inhib-PKA | 60 (uM^-1 s^-1) | 1 (s^-1) | Kd(bf) = 0.0167(uM) | - | PKA-active PKA-inhibitor | inhibited-PKA |
| See Doskeland and Ogreid Int J Biochem 13:1-19. Not clear what the rates are, but the reaction has to be fast and it has to have a pretty high affinity. The exact values are not critical under these conditions. | |||||||
| 6 | Release-C1 | 60 (s^-1) | 18 (uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | R2C2-cAMP4 | PKA-active R2C-cAMP4 |
| The complex starts to dissociate and release the catalytic subunit C. This has to be fast, as the activation of PKA by cAMP is also fast. | |||||||
| 7 | Release-C2 | 60 (s^-1) | 18 (uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | R2C-cAMP4 | PKA-active R2-cAMP4 |
| Second catalytic subunit is now released. | |||||||
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