The Proton Bohr Factor of Native and Crosslinker Treated Hemoglobins - Its Possible Significance for the Efficacy of Hemoglobin Based Artificial Oxygen Carriers

Abstract

Especially the (alkaline) proton Bohr effect seems to provide an important self regulating mechanism of the organism to deliver specifically oxygen into tissues suffering from O2 deficit. In this way these tissues switch from aerobic to anaerobic metabolism, get lactacid, thereby shifting oxygen hemoglobin binding curve to the right and thus facilitating the oxygen release. The higher the absolute value of the proton Bohr factor (: delta logP50/ delta pH) is the better this mechanism works. To get one characteristic number the proton Bohr factor at pH 7.1 is taken. This pH in blood is about a lower limit for organism and human blood has at this pH its maximum proton Bohr factor which is about -0.5. When designing a hemoglobin based artificial oxygen carrier such a high or even a higher proton Bohr factor should be aimed at. But bringing human hemoglobin into extracellular milieu decreases the said proton Bohr effect down to -0.31; about the same values have bovine and porcine hemoglobin under these conditions. Before native hemoglobin can be used as an artificial oxygen carrier outside the red blood cells, they must be crosslinked; otherwise they are cleared quickly by the kidneys. Reaction of human and bovine hemoglobin with the crosslinkers DIBS (2,5- diisothiocyanatobenzenesulfonate) and DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonate) decreases the proton Bohr effect once again substantially down to about -0.1 irrespective of the degree of polymerization (monomer and hyperpolymer). Proton Bohr factors of reaction products from various hemoglobins and different crosslinkers evaluated from measurements of other investigators largely confirm the findings of this study.(ABSTRACT TRUNCATED AT 250 WORDS)