title: Effects of glutaraldehyde polymerization on oxygen transport and redox properties of bovine hemoglobin.
abstract: Crosslinking of bovine Hb (HbBv) with glutaraldehyde produces a mixture of low oxygen affinity (P(50)) tetrameric and polymeric Hb species (PolyHbBv). Under physiological conditions the P(50) of HbBv and PolyHbBv were 27 and 35 mmHg, respectively. The dependence of the P(50) on pH and chloride ions and the cooperativity (n(50)) of the protein were diminished as a result of glutaraldehyde modification. Rapid kinetic studies showed greater overall rates of oxygen dissociation (k(off)) with little or no change in the association of CO (k(on)) to the modified protein. The rate of nitric oxide (NO)-induced oxidation of the PolyHbBv was slightly lower than that of HbBv. Autoxidation rate of PolyHbBv was 1.4 times faster than that of HbBv. The reaction of hydrogen peroxide (H2O2) with the ferrous (Fe(2+)) and ferric (Fe(3+)) forms of the proteins led to the formation of a more stable ferrylHb (Fe(4+)) in the case of PolyHbBv. Glutaraldehyde polymerization of HbBv alters its normal allosteric mechanisms, autoxidation kinetics and other related redox properties, which may compromise its function and cause greater toxicity when used as an oxygen transport fluid.
authors: Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. alayash@cber.fda.gov
authors: A I
authors: AI
authors: Alayash
authors: A G
authors: AG
authors: Summers
authors: F
authors: F
authors: Wood
authors: Y
authors: Y
authors: Jia
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D005976:Glutaral / Q000737:chemistry* / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology
chemical_list: D006454:Hemoglobins; D011108:Polymers; D009569:Nitric Oxide; D010100:Oxygen; D005976:Glutaral