Fine tuning of polymerized pyridoxylated hemoglobin as a red blood cell substitute.

Abstract

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.

• Authors: C J Hsia
• Journal: Progress in clinical and biological research (Prog Clin Biol Res) Vol. 319 Pg. 339-49 ( 1989) ISSN: 0361-7742 [Print] United States
• PMID: 2622918 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Substitutes
• Hemoglobins
• polyhemoglobin-pyridoxal-5-phosphate
• Pyridoxal Phosphate

Topics

• Blood Substitutes (chemical synthesis)
• Hemoglobins (chemical synthesis)
• Molecular Weight
• Pyridoxal Phosphate (analogs & derivatives, chemical synthesis)