Oxyhemoglobin production

Figure 7.9 Delivery of oxygen to peripheral tissue by oxyhemoglobin. Production of protons from COz and HzO, catalyzed by carbonic anhydrase (CA) and their uptake by hemoglobin are also shown. The pC02 in peripheral tissues is high and p02 is low, causing the conversion of hemoglobin R forms into the T forms with the concomitant release of 02. (Reproduced by permission from Bunn HF, Forget BG. Hemoglobin Molecular, Genetic, and Clinical Aspects. Philadelphia WB Saunders, 1986, p. 41.)...

At the moment, only three in vitro studies have been performed on Bfx metabolic behavior, hi one case, it has been shown that Bfxs are able to be reduced by oxyhemoglobin to the corresponding o-nitroaniline derivatives (Scheme 5) [237]. hi the reaction between compoimd 135 and oxyhemoglobin compound 136 was generated as secondary product resulting from both nitrile hydrolysis and deoxygenation. This study indicates that blood is a possible site for metabolism of Bfxs with the consequent methemoglobinemia. 

The reactivity of NO with O2 is dramatically affected upon coordination of one of the diatomic components to a metal center. For example, the second-order reactions of NO with oxyhemoglobin, Hb(02) and oxymyoglobin, Mb(02) (e.g. Eq. (47)) are quite fast and have been used as colorimetric tests for NO (105). The nitrogen product is NO3 rather than N02 that is the product of aqueous autoxidation (106). While the reaction of 02 with nitrosyl myoglobin Mb(NO) (Eq. (48)) might superficially appear similar it is much slower and follows a different rate law (107). Possible mechanisms will be discussed below. 

The main point of argument with the formation of HbSNO is that in vitro the exposure of NO to oxyhemoglobin (HbFe(II)-02) results in the production of methe-moglobin (HbFe(III)) plus nitrate (Eq. (2)). 

Figure 3 Manufacturing scheme for liposome-encapsulated hemoglobin (LEH). Lipid phase is mixed with hemoglobin and the mixture is homogenized in an extruder or a microfluidizer. Unencapsulated hemoglobin is separated by filtration, before PEGylation is performed by postinsertion. The resulting PEG-LEH is converted into oxyhemoglobin form and concentrated to obtain final product. Abbreviation IXC, interaction chamber.

Similarly, amino phenols can be oxidized to semiquinones and quinoneimines. This can be carried out by oxyhemoglobin (Hb-FeII-02). However, the reactive products, semiquinones and quinoneimines can oxidize the hemoglobin to ferrihemoglobin (Hb-Felll), which leads to toxicity as it cannot carry oxygen. 

Labrude and Rasolomana [1.80] reported an atomizer-spray-drying system for oxyhemoglobin in a 0.25 M sucrose solution at temperatures between +80 and +100 °C, which resulted in an unchanged dry product if the relative humidity was kept below 3%. When this dry product was compared with a freeze-dried product, in both cases a met-oxyhemoglobin (met-HBO) content of-3% was found. By ERP and spectro-... 

Superoxide is also a product of various enzyme reactions catalyzed by the flavin oxidases (e.g., xanthine oxidase and monoamine oxidase). In addition, 07 is a product of the noncatalytic oxidation of oxyhemoglobin, of which about 3% is converted each day to methemoglobin. Moreover, 02 is readily formed in phagocytic cells (i.e., neutrophils and monocytes) during the respiratory burst. Furthermore, in addition to the Fenton reaction, the Haber-Weiss reaction results in the conversion of 02 to the potent HO via the following reactions (H3) ... 

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