Interaction of nitrogen monoxide with hemoglobin and the artefactual production of S-nitroso-hemoglobin.
Hemoglobin (Hb) is probably the most thoroughly studied protein in the human body. However, it has recently been proposed that in addition to the well known function of dioxygen and carbon dioxide transporter, one of the main roles of hemoglobin is to store and transport nitrogen monoxide. This hypothesis is highly disputed and is in contrast to the proposal that hemoglobin serves as an NO. scavenger in the blood. In this short review, I have presented the current status of research on the much-debated mechanism of the reaction between circulating hemoglobin and NO.. Despite the fact that oxyHb is extremely rapidly oxidized by NO., under basal physiological conditions the biological activity of NO. in the blood vessels is not completely lost. It has been shown that three factors reduce the efficiency of hemoglobin to scavenge NO.: a so-called red blood cell-free zone created close to the vessel wall by intravascular flow, an undisturbed layer around the red blood cells--where the NO. concentration is much smaller than the bulk concentration--and/or the red blood cell membrane. Alternatively, it has been proposed that NO. binds to Cys beta 93 of oxyHb, is liberated after deoxygenation of Hb, and consequently allows for a more effective delivery of O2 to peripheral tissues. However, because of the extremely fast rate of the reaction between NO. and oxyHb, experiments in vitro lead to artefactual production of large amounts of S-nitroso-hemoglobin. These results, together with other data, which challenge most steps of the NO.-transporter hypothesis, are discussed.
Herold
Susanna
S
Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule, ETH Hönggerberg, CH-8093 Zürich, Switzerland. herold@inorg.chem.ethz.ch
D001808:Blood Vessels / Q000502:physiology; D016166:Free Radical Scavengers; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry*
D016166:Free Radical Scavengers; D006454:Hemoglobins; C103574:S-nitrosohemoglobin; D009569:Nitric Oxide