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Molecule Parameter List for GC5_CO | The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by  color. | | Statistics |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | CO_activation_
of_GC | 28 | Pathway |
sGC | Carbon Monoxide is an activator of soluble Guanylyl Cyclase and has been implicated as a neuronal messenger [Ingi T. et al. Neuron (1996) 16(4):835-42].
CO binds to the heme group on sGC, similar to NO binding. Exogenous CO at similar conc. to endogenous levels were used to study the extent of activation of GC. Olfactory receptor neurons were used by Ingi et al., to investigate the relationship of CO to cGMP levels, as these cells have high levels of HO activity but no NOS activity.
Kharitonov VG. et al. Proc Natl Acad Sci U S A. (1995) 92(7):2568-71 and
Kharitonov VG. et al. Biochemistry (1999) 38(33):10699-706 report the presence of a six coordinate and a five coordinate intermediate of carboxy GC, induced by CO. Considering that activation of sGC by CO is similar in almost all tissues, some rates have been taken from original published works cited as references in Kharitonov et al., and Ingi et al., the primary datasources, this model is based on. |
GC5_CO acting as a Molecule in CO_activation_of_GC Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GC5_CO | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 0 | 0.0016667 | No | | The active five coordinate Carboxy GC. Kharitonov et al., PNAS, 1995, 92:2568-2571 report the presence of a five coord carboxy species during the activation of GC by CO, similar to the presence of a five coord species in the nitroxyl GC, during NO activation of sGC. |
GC5_CO acting as an Enzyme in CO_activation_of_GC Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | GC5_CO /
activeGC
| CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 0.5 | 54.54 | 4 | Classical Michaelis-Menten
V = Etot.S.Kcat/Km+S | Substrate
GTP
Product
cGMP
| | Friebe et al., 1996, EMBO Journal, 15(24): 6863-6868 and back refs cited in their paper. They have studied the potentiation by YC-1 of CO activated sGC. In the absence of YC-1, they report 3 fold stimulation of GC by CO, with 218 +- 11 nmol/min/mg of cGMP. Vmax / Km increased by 100 X. |
GC5_CO acting as a Substrate in a reaction in CO_activation_of_GC Network
| 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 reaction are not consider. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | k | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 1000
(s^-1) | 0
(s^-1) | - | - | Substrate
GC5_CO
Product
dissoCO
| | The dissociation of CO from the active five co-ordinate GC. rate from Kharitonov et al., PNAS, 1995, 92:2568-2571. Further justification include the fact that Soret absorption spectrum of GC-NO suggesting almost complete sonversion to five co-ordinate species. So, assuming that the five co-ord species is more active than the basal form, irrespective of the Ligand, the percentage of five co-ordinate intermediate induced by CO was calculated to be 3% to 1.5%.(Kharitonov et al., 1995, PNAS) using mean value, ~ 2 +- 1 %, and kobs = 28/sec, k = 1*10^3/sec. (Kharitonov et al., PNAS, 1995, 92:2568-2571) |
GC5_CO acting as a Product in a reaction in CO_activation_of_GC Network
| 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 reaction are not consider. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | K | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 0.95
(s^-1) | 0
(s^-1) | - | - | Substrate
GC6-CO
Product
GC5_CO
| | The transition from six co-ordinate to the five co-ordinate carboxy GC. CO dissociation rate for 6 coord sp for heme is 0.95 /sec. (Kharitonov et al., 1995, PNAS, 92:2568-2571) |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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