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Molecule Parameter List for 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. |
CO acting as a Molecule in CO_activation_of_GC Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | CO | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 0 | 0.0016667 | No | | CO is an endogenous modulator of sGC. It is produced by the oxidative cleavage by HO to yield CO and Biliverdin. It also binds to the heme group on sGC as NO and it may be competetive to NO with regard to the binding to the heme prosthetic group. Like NO, it binds to the Iron in the heme, and activate Guanylyl Cyclase. (Brune et al., 1987, Mol. Pharmacol.32, 497-504), Kharitonov et al., 1995, PNAS, 92:2568-2571) Because of the gaseous nature of CO, and its high affinity for hemoprotein, its very difficult to determine the exact intracellular concentration of CO. Endogenous CO level was calculated to be 50-160 pmol/mg protein or 10-30 uM, by Ingi et al., J Neursoci 1996, 16(18): 5621-5628, on the assumption that the amount of CO produced for 10-30 mins is an effective concentration in the cell, taking into account the diffusion of CO. Using exogenous CO at the endogenous levels of 10-30 uM, significant elevation of GC activity is observed, though CO does not seem to be a rapid stimulator, but works as a modulator, producing slower and long-term effects (Ingi et al., 1996, J Neurosci.,16(18):5621-5628). |
CO acting as a Product of 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 | Hemeoxyg2 /
HOXY | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 3.80004 | 0.3556 | 4 | explicit E-S complex | Substrate
Heme
Product
CO
| | Ingi et al., J Neurosci., 1996, 16(18):5621-5628, report the production rates of heme precursors and metabolites. The rate reported for CO from heme is 2.9 pmol/mg protein over 6 hr. Their results indicate high HO activity in brain (along with significant levels of heme) at around 280pmol of bilirubin/mg/min. Montellano PRO, Curr. Opin. in Chem. Biol, 2000,4:221-227 and refs cited in his paper were also studied initially. Km for free heme is around 3.8 +/- 0.5 uM.(Bonkovsky et al., 1990, 189(1):155-166) |
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 | | CObindsGCa | CO_activation_
of_GC
Accession No. : 28 | sGC
Pathway No. : 140 | 0.12
(uM^-1 s^-1) | 28
(s^-1) | Kd(bf) = 233.3333(uM) | - | Substrate
CO
sGC
Product
GC6-CO
| | This gives rise to the six co-ordinate carboxy GC. Kharitonov et al., 1995, PNAS, 92:2568-2571 report CO association and dissociation rates at 1.2e5 /M/sec and 28 /sec respectively. Kharitonov et al., 1999, Biochemistry, 38(33):10699-10706 report Ka at 7.86 +- 0.50 /mM. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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