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PKC
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CaMKII
CaM
PP1
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PKA
AC
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CaRegulation

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Molecule List for pathway AC (Pathway Number 85)

 Name Initial Conc. (uM) Volume (fL) Buffered
1AC10.021000No
    AC concentrations are tricky due to poor antibodies. I refer to an estimate from Jacobowitz, PhD Thesis, Mount Sinai School of Medicine around Pg 149 which estimates cyclase as 1/12600 of membrane protein. This gives a whole-cell conc of about 33 nM using assumptions of 2% of cell mass being membrane protein. Defer et al 2000 Am J Physiol Renal Physiol 279:F400-F416 in a good review put AC1 and AC8 (which has similar properties) as among the highly expressed form of brain cyclase. We therefore estimate its levels as a good fraction of the 33 nM, at 20 nM.
2AC1-CaM01000No
    This state of AC1 is bound to Calmodulin and therefore activated. Gs stimulates it but betagamma inhibits.
3AC1-Gs01000No
    This is the generic Gs-Stimulated state of AC1. Note that the enzyme is normally saturated, so all reactions involving AC1-Gs actually relate to the enzyme-substrate complex.
4AC20.0151000No
    AC concentrations are tricky due to poor antibodies. I refer to an estimate from Jacobowitz, PhD Thesis, Mount Sinai School of Medicine around Pg 149 which estimates cyclase as 1/12600 of membrane protein. This gives a whole-cell conc of about 33 nM using assumptions of 2% of cell mass being membrane protein. Defer et al 2000 Am J Physiol Renal Physiol 279:F400-F416 in a good review put AC2 among the highly expressed form of brain cyclase. We therefore estimate its levels as a good fraction of the 33 nM, at 15 nM. This actually adds up to a little more than 33, but it is well within error estimates.
5AC2*01000No
    This is the phosphorylation-activated form of AC2.
6AC2*-Gs01000No
    This is the form activated synergistically by phosphorylation as well as Gs binding.
7AC2-Gs01000No
    This is the generic Gs-Stimulated form of AC2
8AMP100.0016667Yes
    AMP is a tightly regulated metabolite, so here we simply buffer it to its resting value. The value doesn't really matter to any of the calculations since it acts like a one-way sink.
9ATP50001000Yes
    ATP is present in all cells between 2 and 10 mM. See Lehninger.
10CaM.PDE101000No
    PDE1 is the 66 KDa form which binds CaM. Borisy et al J Neurosci 12(3):915-923 report a 6x stimulation with calcium.
11cAMP-PDE0.451000No
    The levels of the PDE are not known at this time. However, enough kinetic info and info about steady-state levels of cAMP etc are around to make it possible to estimate this.
12cAMP-PDE*01000No
    This form has about 2X activity as plain PDE. See Sette et al JBC 269:28 18271-18274 1994.
13PDE121000No
    CaM-Dependent PDE. 66KDa Borisy et al J Neurosci 12(3):915-923 About 0.6% of membrane protein. so estimate 2 uM as conc in brain. Also see Conti et al Adv Sec Mess Phosphoprotein Res 1992 25:87-99


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