| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | PLC-Gq | PLCbeta
Pathway No. 112 | Network | 0 | 1000 | No | - |
| | from Smrcka et al, 1991 Science 251: 804-807 |
| 2 | PLC-Ca | PLCbeta
Pathway No. 112 | Network | 0 | 1000 | No | - |
| | From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al. k1 = 1.5e-5, now 4.2e-6 k2 = 70/sec; now 40/sec k3 = 17.5/sec; now 10/sec Note that the wording in Sternweis et al is ambiguous re the Km. Also Smrcka et al; Science 251, 15.2.1991, pp804-807 |
| 3 | PLC-Ca-Gq | PLCbeta
Pathway No. 112 | Network | 0 | 1000 | No | - |
| | This should really be labelled PLC-Ca-GTP.Gq_alpha This is the most active form of the enzyme. |
| 4 | PLC | PLCbeta
Pathway No. 112 | Network | 0.04 | 1000 | No | - |
| | Smrcka et al; Science 251, 15.2.1991, pp804-807 |
| 5 | DAG | PLCbeta
Pathway No. 112 | Network | 0 | 1000 | No | - |
| | Basal levels of Diacylglycerol in model are 5.06 uM. DAG is pretty nasty to estimate. Data sources are many and varied and sometimes difficult to reconcile. Welsh and Cabot 1987 JCB 35:231-245: DAG degradation Bocckino et al JBC 260(26):14201-14207: hepatocytes stim with vasopressin: 190 uM. Bocckino et al 1987 JBC 262(31):15309-15315: DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM. Prescott and Majerus 1983 JBC 258:764-769: Platelets: 6 uM. Also see Rittenhouse-Simmons 1979 J Clin Invest 63. Sano et al JBC 258(3):2010-2013: Report a nearly 10 fold rise. Habenicht et al 1981 JBC 256(23)12329-12335: 3T3 cells with PDGF stim: 27 uM Cornell and Vance 1987 BBA 919:23-36: 10x rise from 10 to 100 uM |
| 6 | PC | PLCbeta
Pathway No. 112 | Network | 0 | 1000 | Yes | - |
| | Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987) |
| 7 | PIP2 | PLCbeta
Pathway No. 112 | Network | 150 | 1000 | Yes | - |
| | PIP2 conc: Willars et al; JBC 273 (9) 27.2.98; pp 5037-5046 |
| 8 | PKC-DAG-AA* | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | Membrane translocated form of PKC-DAG-AA complex. |
| 9 | PKC-Ca-AA* | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | Membrane bound and active complex of PKC, Ca and AA. |
| 10 | PKC-Ca-memb* | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | This is the direct Ca-stimulated activity of PKC. |
| 11 | PKC-DAG-memb* | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | Active, membrane attached form of Ca.DAG.PKC complex. |
| 12 | PKC-basal* | PKC
Pathway No. 108 | Network | 0.02 | 1000 | No | - |
| | This is the basal PKC activity which contributes about 2% to the maximum. |
| 13 | PKC-AA* | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | This is the membrane-bound and active form of the PKC-AA complex. |
| 14 | PKC-Ca-DAG | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | This is the active PKC form involving Ca and DAG. It has to translocate to the membrane. |
| 15 | PKC-DAG | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | This is a DAG-bound intermediate used in synergistic activation of PKC by DAG and AA. |
| 16 | PKC-DAG-AA | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | Complex of PKC, DAG and AA giving rise to synergistic activation of PKC by DAG and AA at resting Ca. |
| 17 | PKC-cytosolic | PKC
Pathway No. 108 | Network | 1 | 1000 | No | - |
| | Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells Kikkawa et al 1982 JBC 257(22):13341 have PKC levels in brain at about 1 uM. The cytosolic form is the inactive PKC. This is really a composite of three isoforms: alpha, beta and gamma which have slightly different properties and respond to different combinations of Ca, AA and DAG. |
| 18 | PKC-Ca | PKC
Pathway No. 108 | Network | 0 | 1000 | No | - |
| | This intermediate is strongly indicated by the synergistic activation of PKC by combinations of DAG and Ca, as well as AA and Ca. PKC by definition also has a direct Ca-activation, to which this also contributes. |
| 19 | AA | PKC
Pathway No. 108 | Network | 50 | 1000 | Yes | - |
| | Arachidonic Acid. This messenger diffuses through membranes as well as cytosolically, has been suggested as a possible retrograde messenger at synapses. |
| 20 | PKC-active | PKC
Pathway No. 108 | Network | 0 | 1000 | No | PKC-DAG-AA*
PKC-Ca-memb*
PKC-Ca-AA*
PKC-DAG-memb*
PKC-basal*
PKC-AA*
|
| | This is the total active PKC. It is the sum of the respective activities of PKC-basal* PKC-Ca-memb* PKC-DAG-memb* PKC-Ca-AA* PKC-DAG-AA* PKC-AA* I treat PKC here in a two-state manner: Either it is in an active state (any one of the above list) or it is inactive. No matter what combination of stimuli activate the PKC, I treat it as having the same activity. The scaling comes in through the relative amounts of PKC which bind to the respecive stimuli. The justification for this is the mode of action of PKC, which like most Ser/Thr kinases has a kinase domain normally bound to and blocked by a regulatory domain. I assume that all the activators simply free up the kinase domain. A more general model would incorporate a different enzyme activity for each combination of activating inputs, as well as for each substrate. The current model seems to be a decent and much simpler approximation for the available data. One caveat of this way of representing PKC is that the summation procedure assumes that PKC does not saturate with its substrates. If this assumption fails, then the contributing PKC complexes would experience changes in availability which would affect their balance. Given the relatively low percentage of PKC usually activated, and its high throughput as an enzyme, this is a safe assumption under physiological conditions. |
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