A Novel Possible Role for Met Hemoglobin as Carrier of Hydrogen Sulfide in the Blood

Recent Advances: Recent in vitro evidence suggests that H2S at low physiological concentrations is carried in the blood as bound to the small fraction of oxidized ferric hemoglobin (metHb). A relatively stable metHb-sulfide complex forms when H2S and purified metHb react in vitro, with an affinity within the in vivo physiological range of sulfide in the blood. Formation and subsequent redox metabolism of metHb-sulfide complex have also been confirmed in isolated intact red blood cells (RBCs) containing enhanced metHb levels. Thus, H2S may function as an endocrine signaling molecule and elicit responses at sites away from the site of production. In addition, metHb, considered as an inert or pathological hemoglobin derivative, may have a novel potential physiological role in the transport of H2S in the blood. Critical Issues: The transport of H2S in the blood mediated by metHb would represent an O-2-independent pH-dependent mechanism for the blood-mediated control of blood flow and as such it is critical to understand the in vivo significance of this transport. Future Directions: Major challenges must be resolved to understand how metHb may carry H2S in the RBCs, in particular determination of metHb-sulfide levels in the blood and identification of targets in the vasculature.