Reactivity of the human hemoglobin “Dark side”

Abstract

Ligand binding to the heme distal side is a paradigm of biochemistry. However, X-ray crystallographic studies highlighted the possibility that O(2) and NO(2) (-) may bind to the proximal heme side of ferrous human hemoglobin (Hb) α-chains complexed with the α-hemoglobin stabilizing protein and to ferric human hemoglobin β-chains, respectively. Strikingly, the role generally played by the proximal HisF8 residue is played by the distal HisE7 side chain forming the trans axial ligand of the heme-Fe atom. This: i) brings to light that Hb may utilize both heme distal and proximal sides for ligand discrimination, ii) draws attention to the nonequivalence of α- and β-chains, and iii) highlights the possibility that partially unfolded Hb derivatives may display transient ligand-binding properties different from those of the native globin.

Resonance Raman in Vitro Detection and Differentiation of the Nitrite-Induced Hemoglobin Adducts in Functional Human Red Blood Cells

“…As was previously reported, because NO 2 − is an important biochemical signaling molecule and a source of the bioavailable NO, 20 the addition of NaNO 2 to the RBCs cannot be treated just as a way of metHb production. In vitro observation of previously reported, various stable Hb 3+ NO 2 5 and Hb 3+ NO 6 adducts after NaNO 2 treatment in functional RBCs may shed new light on the explanation of a complex autocatalytic reaction between oxyHb and nitrite ions. It was additionally reported on Hb standard that a nitrite ion may bind reversibly to ferriheme under physiological conditions.…”

“…Previous works suggested that several intermediates may be involved in this complicated, autocatalytic, free-radical chain reaction; however, later studies suggest that H 2 O 2 and NO 2 play the most important roles as initiator and autocatalytic propagator species, respectively . Some other species, besides metHb, such as, hemichromes, HbNO 2, or Hb 3+ NO/Hb 2+ NO, have also been reported to be generated from this well-recognized Hb–nitrite reaction. In those studies, metHb should be understood as the aquomethemoglobin (metHb–H 2 O), with hematin as a prosthetic group and water and histidine molecules as ligands in axial positions. , The crystal structure of the T-state and R-state human metHb–H 2 O has been previously reported …”

Cardiolipin-cytochromeccomplex: Switching cytochromecfrom an electron-transfer shuttle to a myoglobin- and a peroxidase-like heme-protein

“… CL facilitates allosterically NO and CO binding to horse heart cyt c (II) , which undergoes nitrosylation very slowly and carbonylation not at all in the absence of CL. In addition, CL induces NO binding to the proximal site of the cyt c (II) heme pocket (Scheme ). In contrast, CO binds to the heme distal site CL–cyt c (III) with a simple mechanism (Scheme ).…”