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Accession Type:
Network
Synaptic_
Network
Shared_Object_
Synaptic_
Network
PKC
PLA2
PLCbeta
Gq
MAPK
Ras
EGFR
Sos
PLC_g
CaMKII
CaM
PP1
PP2B
PKA
 Molecule
 Reaction
AC
CaRegulation

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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 KfKbKdtauSubstrateProduct
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-PKA60
(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-C160
(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-C260
(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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