Carbon monoxide hemes

There is at present limited information on the sites of action of carbon monoxide. Hemes and cytochromes are the most likely sites. However, direct evidence is generally missing with the exception of guanylyl cyclase. 

FIGURE 15.26 Oxygen and carbon monoxide binding to the heme group of myoglobin. 

Carbon Monoxide. Figure 1 Heme oxygenase catalyzed heme metabolism (from Pharmacol Rev 57 585-630,... 

Besides NO, other sGC-activating substances have been reported Carbon monoxide (CO) is known to bind to heme groups with high affinity but has been shown to activate the enzyme only marginally (three- to fivefold). The compound YC-1 ([3-(5 -hydroxymethyl-2 -fury 1)-1-benzyl indazole]) is a prototype of a new class of so-called NO-sensitisers. YC-1 causes a tenfold activation of NO-sensitive GC. Pharmacologically more interesting, YC-1 increases GC s sensitivity towards NO and CO suggesting potential beneficial effects of... 

Figure 6-3. Angles for bonding of oxygen and carbon monoxide to the heme iron of myoglobin. The distal E7 histidine hinders bonding of CO at the preferred (180 degree) angle to the plane of the heme ring.

The structural and functional integrity of organoclay-wrapped Mb and Hb molecules was demonstrated by retention of the secondary protein structure as well as distinctive shifts in the absorption spectra associated with oxygen or carbon monoxide binding to the heme metallocenter. The latter indicated that the wrapped... 

HRP C contains two different types of metal center (i.e., iron(III) protoporphyrin IX-heme group and two calcium atoms) that are fundamental for the integrity of the enzyme. The heme group is attached to the enzyme at His 170 by a coordinate bond between the histidine side-chain NE2 atom and the heme iron atom. The second axial coordination site is unoccupied in the resting state of the enzyme but available to hydrogen peroxide during enzyme turnover. Small molecules such as carbon monoxide, cyanide, fluoride, and azide bind to the heme iron atom at this distal site, giving six-coordinated PX complexes. 

Hydroxyurea reacts with oxy, deoxy and metHb in vitro to form iron nitrosyl hemoglobin (HbNO) and transfers NO to 2-6% of the iron heme groups [115]. Trapping studies using cyanide and carbon monoxide indicate that hydroxyurea oxidizes both oxy and deoxyHb to metHb and reduces metHb to deoxyHb specifically identifying the reaction of hydroxyurea and metHb as the critical reaction in the formation of HbNO from hydroxyurea [115]. Scheme 7.16 depicts the proposed mechanisms of N O and HbNO formation during the reaction of deoxy and metHb with hydroxyurea. Oxidation of hydroxyurea by metHb produces deoxyHb and the nitroxide radical (25,... 

McMillan, K., Bredt, D. S., Hirsch, D. J., Snyder, S. H., Clark, J. E., Masters, B. S., Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide, Proc. Natl. Acad. Sci. USA 89 (1992), p.11141-11145... 

Table 8. Observed first order rate constants (ko, s.) for the displacement of dioxygen in the hemes Fe(TPP)02L ([79] M = Fe, X = O2) by carbon monoxide (Eq. 4) at - 79 °C in CH2CI2 (30)...

Heme metabolized in histiocytes Production of biliverdin releases carbon monoxide (CO)... 

Not only is carbon monoxide produced during catabolism of hemes, but it is also necessary for maintenance of neuronal function and cell signaling in the vasculature and therefore is present normally in the vicinity of Mb and Hb. For synthetic systems of picket-fence, pocket, or capped porphyrins, CO affinity exceeds that for O2 sometimes by many orders of magnitude. The in... 

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