The quaternary structure of tetrameric hemoglobin regulates the oxygen affinity of polymerized hemoglobin |
| |
Authors: | Andre F Palmer Guoyong Sun David R Harris |
| |
Institution: | William G. Lowrie Dept. of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210 |
| |
Abstract: | This study focuses on the effect of the initial quaternary structure of bovine hemoglobin (Hb) on the physical properties of glutaraldehyde polymerized Hb (PolyHb) solutions. Tense (T) state PolyHb was synthesized by maintaining the pO2 of Hb before and after polymerization at 0 mm Hg. In contrast, relaxed (R) state PolyHb was generated by maintaining the pO2 of Hb before and after polymerization to >749 mm Hg. PolyHb solutions were characterized by measuring the pO2, methemoglobin (metHb) level, molecular weight distribution, O2 affinity and cooperativity coefficient. The metHb level of all PolyHb solutions was low (<2%). Analysis of the molecular weight distribution of PolyHb solutions indicates that in general, the molecular weight of PolyHb solutions increased with increasing cross‐link density. T‐state PolyHb solutions exhibited lower O2 affinity compared to unmodified Hb, whereas R‐state PolyHb solutions exhibited higher O2 affinity compared to unmodified Hb. In addition, the polymerization reaction resulted in a significant decrease in cooperativity that was more pronounced at higher cross‐link densities. All of these results were explained in terms of the quaternary structure of Hb. Taken together, our results yield more insight into the importance Hb's quaternary structure plays in defining the physical properties of glutaraldehyde PolyHb solutions. This information will be useful in designing optimized glutaraldehyde PolyHb oxygen carriers for various applications in transfusion medicine. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. 2009 |
| |
Keywords: | hemoglobin oxygen carrier blood substitute polymerization cross‐link quaternary structure glutaraldehyde polymerized hemoglobin |
|
|