Fine tuning of polymerized pyridoxylated hemoglobin as a red blood cell substitute.
Hemoglobin (Hb), modified by pyridoxal 5'-phosphate (PLP) and polymerized by glutaraldehyde (GA) to yield polymerized pyridoxylated Hb (Poly-PLP-Hb), is currently the prime candidate for a hemoglobin-based red cell substitute. However, hematuria and excessive oxygen-binding affinity have been associated with poly-PLP-Hb after transfusion. These phenomena have not yet been explained. In the present communication, we show that pyridoxylation, which is known to reduce the oxygen-binding affinity of Hb to physiological levels, also inhibits the subsequent polymerization of Hb by GA. We attribute poly-PLP-Hb associated hematuria and high oxygen affinity to rapid elimination of these unpolymerized Hb species, leaving in the circulation the polymerized, less-highly pyridoxylated species with excessive oxygen-binding affinity. We proposed a mechanism for PLP inhibition of Hb polymerization, and discuss the implications of our findings for quality control in the preparation of poly PLP-Hb as a red cell substitute.
Hsia
C J
CJ
Hemosol Inc., Etobicoke, Ontario, Canada.
D001802:Blood Substitutes / Q000138:chemical synthesis*; D006454:Hemoglobins / Q000138:chemical synthesis*; D008970:Molecular Weight; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D001802:Blood Substitutes; D006454:Hemoglobins; C030939:polyhemoglobin-pyridoxal-5-phosphate; D011732:Pyridoxal Phosphate