Hsia C J
Hemosol Inc., Etobicoke, Ontario, Canada.
Prog Clin Biol Res. 1989;319:339-49.
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.
血红蛋白（Hb）经5'-磷酸吡哆醛（PLP）修饰并由戊二醛（GA）聚合以产生聚合吡哆醛化血红蛋白（Poly-PLP-Hb），目前是基于血红蛋白的红细胞替代物的主要候选者。然而，输血后血尿和过高的氧结合亲和力与Poly-PLP-Hb有关。这些现象尚未得到解释。在本通讯中，我们表明，已知能将Hb的氧结合亲和力降低至生理水平的吡哆醛化作用，也会抑制随后GA对Hb的聚合作用。我们将与Poly-PLP-Hb相关的血尿和高氧亲和力归因于这些未聚合的Hb物种的快速清除，使具有过高氧结合亲和力的聚合程度较低、吡哆醛化程度较低的物种留在循环中。我们提出了PLP抑制Hb聚合的机制，并讨论了我们的发现对制备作为红细胞替代物的聚PLP-Hb的质量控制的影响。
