New Roles Assigned to the α1–β1 (and α2–β2) Interface of the Human Hemoglobin Molecule from Physiological to Cellular

Abstract

Cellular life is reliant upon rapid and efficient responses to internal and external conditions. The basic molecular events associated with these processes are the structural transitions of the proteins (structural protein allostery) involved.

New Mode (Molecular-Sensing) of Heinz Body Formation Mechanisms Inherent in Human Erythrocytes: Basis for Understanding of Clinical Aspects of Drug-Induced Hemolytic Anemia and the Like

“…The β chains thus acquire pH-dependent delayed autoxidation in the HbO 2 tetramer. The next role was suggested by our studies searching for similar phenomena in normal human erythrocytes under mild heating [17,32,33]. It seemed that tilting of the distal (E7) His in turn triggers degradation of the Hb molecule to hemichrome, and subsequent clustering of Heinzbodies within the erythrocyte.…”

“…Third, in contrast to the tetrameric human HbO 2 as O 2 -carrying protein in the blood, the monomeric bovine heart Mb (MbO 2 ) did not show any propensity for hemichrome formation over a wide pH range of 4.5 to 10.5 and over a wide temperature range from physiological to temperatures just before thermal unfolding. Fourth, in terms of pH-dependent biphasic autoxidation (k A f for the initial fast oxidation and k A s for the second oxidation) seen in acidic solutions, participation of a single dissociation group of an amino-acid residue (probably a His residue) with pK a =7.4 (at 37°C) appeared to have a key role in how the Hb Table 2: Summary of the mean ± standard deviation of transit time of blood samples (s) for a given transit sample volume (μL),redrawn from Sugawara et al [33]. Prior to application to MC-FAN, blood samples were subjected to mild heating at 37°C, 42°C and 45°C for 30 min, respectively.…”

“…Moreover, our recent measurements (UV/VIS spectrophotometry, isoelectric-focusing electrophoresis, and polyacrylamide gel electrophoresis) for autoxidation of human HbO 2 [33] revealed that only two valency hybrids, i.e., (α ). These had satisfactory-to-good consistency with those reported by Tomoda et al [15,[62][63][64][65][66][67].…”

“…The transit sample volume is therefore equivalent to the loss of the blood sample within the cylinder. Here we look into our in vitro findings on blood fluidity during mild heating using a MC-FAN (HR300; Hitachi Haramachi Electronics Co., Ibaraki, Japan) [32,33].…”

“…Herein we consider the results of our study investigating the formation of Heinz bodies in normal human erythrocytes [32][33][34]. Aliquots of freshly drawn venous blood from healthy donors were subjected to mild heating at desired temperature above 37°C for 30 min to investigate hemichrome formation and subsequent Heinzbody formation in normal human erythrocytes.…”