Redox Reactions of Hemoglobin: Mechanisms of Toxicity and Control

Abstract

In the last several years, significant work has been done studying hemoglobin (Hb) oxidative reactions and clearance mechanisms using both in vitro and in vivo model systems. One active research area involves the study of molecular chaperones and other proteins that are thought to mitigate the toxicity of acellular Hb. For example, the plasma protein haptoglobin (Hp) and the pre-erythroid protein alpha-hemoglobin-stabilizing protein (AHSP) bind to acellular Hb and alpha-subunits of Hb, respectively, to reduce these adverse effects. Moreover, there has been significant work studying hemopexin and alpha-1 microglobulin, both of which are thought to be involved with hemin degradation. These studies have coincided with the timely publication of the first crystal structure of the Hb-Hp complex. In constructing this Forum, we have invited a number of researchers in the area of Hb and myoglobin (Mb) redox biochemistry, as well as those who have contributed fundamentally to our knowledge of Hp function. Our goal has been to update this critically important research area, because we believe that it will ultimately impact the practice of transfusion medicine in a number of important ways.

Determination of extinction coefficients of human hemoglobin in various redox states

“…It is becoming increasingly evident that heme loss after Hb oxidation plays a significant role in the toxicity associated with acellular Hb [1–4]. Superoxide ions (O 2 ˙− ) and hydrogen peroxide (H 2 O 2 ) formed during the autooxidation of Hb drive a catalytic cycle that oxidizes ferrous (HbFe 2+ ) into ferric (met) (Hb Fe 3+ ), ferryl (HbFe 4+ ), and the ferryl radical (·HbFe 4+ ) [5, 6]. The catalytic cycle known as the pseudoperoxidase reaction is represented by equations 1 to 3.…”

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

“…O xidative stress and the generation of free radicals are fundamental initiating mechanisms within the red blood cell (RBC) ultimately leading to morbidity and death from many inherited hemoglobinopathies, including sickle-cell anemia, SC disease, b-thalassemia, and HbE/b-thalassemia (HbE/b-thal) (114,200) (Fig. 1).…”

Role of Alpha Hemoglobin Stabilizing Protein Expression in Beta Thalassemia Patients

“…is an erythroid scavenger protein that quickly and reversibly binds to α subunit monomeric forms. It also enhance modulation of oxidation of heme iron and subunit folding [5] . AHSP, known as an alpha-hemoglobin ( α -Hb) chaperone which specifically recognizes the of α -Hb G and H helices, forming a steady complex with free α -Hb till it bind its β -subunits partner.…”