Heme proteins methemoglobin

In vivo heme is released into the plasma by erythrocyte lysis in the form of hemoglobin and by tissue trauma in the form of myoglobin, and both heme proteins are quickly oxidized to their ferric heme forms (methemoglobin and metmyoglobin) at the oxygen tension found in tissue capillary beds. 

Fig. 1. Overview of intravascular heme catabolism. Hemoglobin, myoglobin, and other heme proteins are released into the circulation upon cellular destruction, and the heme moiety is oxidized by O2 to the ferric form (e.g., methemoglobin and metmyoglobin). Haptoglobin can bind a substantial amount of hemoglobin, but is readily depleted. Ferric heme dissociates from globin and can be bound by albumin or more avidly by hemopexin. Hemopexin removes heme from the circulation by a receptor-mediated transport mechanism, and once inside the ceU heme is transported to heme oxygenase for catabolism.

Sharma VS, Isaacson RA et al (1983) Reaction of nitric oxide with heme proteins studies on metmyoglobin, opossum methemoglobin, and microperoxidase. Biochemistry 22 3897-3902... 

Other proteins such as methemoglobin and metmyoglobin have been observed to produce molecular oxygen in the presence of hydrogen peroxide, but at a very low rate (5). This may simply be a property of the heme, which can promote a low-level catalatic reaction in the absence of protein. Consequently, it is possible that all heme-containing proteins may exhibit catalatic reactions if assayed carefully, but such minor, largely nonquantifiable activities are not considered here. 

Heme dissociates from methemoglobin or metmyoglobin in the circulation and can be boimd by hemopexin or albumin, a heme binding plasma protein of lower avidity than hemopexin (49). It is important that the heme be controlled, since this amphipathic, oxidatively active compound can nonspecifically associate with membrane lipids or lipoproteins and cause oxidative damage of vital biomolecules, including DNA (50, 51). 

The most important mechanism that underlies the MR appearance of ICH is the transformation of initially oxygenated hemoglobin into a series of breakdown products (deoxyhemoglobin, methemoglobin, and hemosiderin), that differ in terms of presence and number of unpaired electrons of the heme iron. Hereafter, we will discuss the influence of hemoglobin and its metabolites on T1 and T2 relaxation times. We will also briefly review the effects on MR signals of other factors such as protein concentration, clot formation and retraction, and red blood cell dehydration. 

When the taurine chloramine uptake rate exceeds the rate of NADPH-dependent regeneration of GSH, there is a net loss of cellular GSH level, causing protein-thiol oxidation, ATP loss, and disruption of cellular metabolism. Heme moieties are the other target of chloramine attack on cellular constituents. Oxidation of hemoglobin to methemoglobin (and other hemoproteins to their oxidized derivatives) occurs at 10-fold excess of chloramine taurine molar concentration compared... 

Chapters 11,18). It binds to the iron of heme groups in either the Fe or Fe " form and also reacts with thiol groups of proteins and small molecules to form S-nitrosothiols (R-S-N=0). It reacts with the heme iron of myoglobin and hemoglobin and, by transfer of one electron, can oxidize the iron of hemoglobin to the Fe + methemoglobin with formation of the nitroxyl ion NO This reaction may be a... 

Heme-containing proteins are also targets of -NO. Indeed, in vivo, quantitatively the major reaction of -NO is undoubtedly its reaction with oxyhemoglobin in the circulation to produce nitrate and methemoglobin... 

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