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Molecule Parameter List for dissoCO

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
dissoCO participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1000011

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • CO_activation_
    of_GC
  • 28Pathway
    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.

    dissoCO acting as a Molecule in  
    CO_activation_of_GC Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    dissoCO
  • CO_activation_
    of_GC

    Accession No. : 28
  • sGC
    Pathway No. : 140
    0.11420.0016667Yes
    The erythrocyte-associated hemoglobin has a critical role of being the primary CO-scavenging system. Locally generated CO is eliminated by hemoglobin in circulating erythrocytes and is gradually released into the alveolar space of the lung, where molecular oxygen is alternately bound to the heme. Most of the CO (Carbon Monoxide) generated in the body is exhaled into the airway. (Suematsu M, Gasteroenterology 2001;120:1227-1240 and personal correspondence)

    dissoCO 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.
    NameAccession NamePathway NameKfKbKdtauReagents
    CObindsHbO2
  • CO_activation_
    of_GC

    Accession No. : 28
  • sGC
    Pathway No. : 140
    0.17
    (uM^-1 s^-1)
    0.0078
    (s^-1)
    Kd(bf) = 0.0459(uM)-Substrate
    Ery_HbO2
    dissoCO

    Product
    COHb
    CO binds to hemoglobin, predominantly the erythrocyte associated hemoglobin. The affinity of hemoglobin for CO is 200-250 times that of oxygen, while relative affinities of heme proteins (myoglobin), cytochrome oxidase and cytochrome P-450 for CO are much lower. CO binds reversibly to hemoglobin to form Carboxy hemoglobin, (COHb) from which CO is exhaled through the lungs. Primary source for rates, Migita et al., JBC, 1998, 273(2): 945-949, and refs cited in their paper.

    dissoCO 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.
    NameAccession NamePathway NameKfKbKdtauReagents
    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)



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