title: Pathway and mechanism of pH dependent human hemoglobin tetramer-dimer-monomer dissociations.
abstract: Hemoglobin dissociation is of great interest in protein process and clinical medicine as well as in artificial blood research. However, the pathway and mechanisms of pH-dependent human Hb dissociation are not clear, whether Hb would really dissociate into monomers is still a question. Therefore, we have conducted a multi-technique investigation on the structure and function of human Hb versus pH. Here we demonstrate that tetramer hemoglobin can easily dissociate into dimer in abnormal pH and the tetramer → dimer dissociation is reversible if pH returns to normal physiological value. When the environmental pH becomes more acidic (<6.5) or alkaline (>8.0), Hb can further dissociate from dimer to monomer. The proportion of monomers increases while the fraction of dimers decreases as pH declines from 6.2 to 5.4. The dimer → monomer dissociation is accompanied with series changes of protein structure thus it is an irreversible process. The structural changes in the dissociated Hbs result in some loss of their functions. Both the Hb dimer and monomer cannot adequately carry and release oxygen to the tissues in circulation. These findings provide a comprehensive understanding on the pH-dependent protein transitions of human Hb, give guideline to explain complex protein processes and the means to control protein dissociation or re-association reaction. They are also of practical value in clinical medicine, blood preservation and blood substitute development.
authors: Department of Biomedical Engineering, Ji Nan University, Guang Zhou, China.
authors: Yao-Xiong
authors: YX
authors: Huang
authors: Zheng-Jie
authors: ZJ
authors: Wu
authors: Bao-Tian
authors: BT
authors: Huang
authors: Man
authors: M
authors: Luo
mesh_terms: D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D006454:Hemoglobins