| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | cAMP-bind-site-B
1 | PKA
Pathway No. 84 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2
cAMP
Products:
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. | | 2 | cAMP-bind-site-B
2 | PKA
Pathway No. 84 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2-cAMP
cAMP
Products:
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 | | 3 | cAMP-bind-site-A
1 | PKA
Pathway No. 84 | 75
(uM^-1 s^-1) | 110
(s^-1) | Kd(bf) = 1.4667(uM) | - | Substrate:
R2C2-cAMP2
cAMP
Products:
R2C2-cAMP3
|
| This site has a higher Kd for cAMP. See Ogreid and Doskeland 1982 FEBS Lett 150:1 161-166 | | 4 | cAMP-bind-site-A
2 | PKA
Pathway No. 84 | 75
(uM^-1 s^-1) | 32.5
(s^-1) | Kd(bf) = 0.4333(uM) | - | Substrate:
cAMP
R2C2-cAMP3
Products:
R2C2-cAMP4
|
| Cooperativity kicks in, now we have a low Kd for cAMP. | | 5 | Release-C1 | PKA
Pathway No. 84 | 60
(s^-1) | 18
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C2-cAMP4
Products:
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. | | 6 | Release-C2 | PKA
Pathway No. 84 | 60
(s^-1) | 18
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C-cAMP4
Products:
PKA-active
R2-cAMP4
|
| Second catalytic subunit is now released. | | 7 | inhib-PKA | PKA
Pathway No. 84 | 60
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate:
PKA-active
PKA-inhibitor
Products:
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. |
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