Online edition:ISSN 2758-089X

Instability of Hemoglobin Molecule ― A Review. Part I.

The stability and solubility of hemoglobin (Hb) molecule depends upon an ordered tertiary structure and requires that each globin chain undergoes a minimum conformational changes. There are several processes by which the stability of hemoglobin molecule can be affected. Of many, the most common involves the replacement of those amino acids which are either in direct contact with heme group or in the viscinity of heme pocket. Substitution at the α1β1 contact can result in weakening of the linkages. Deletion of certain amino acids residues from a polypeptide chain of hemoglobin is known to disrupt the secondary structure of the molecule itself. The subunit structure can also be affected due to replacement of helical residue by a proline residue. In many cases the stability of the molecule is also associated with oxidative changes in the molecule producing methemoglobin. There are also examples in which the instability of Hb molecule is self-causing due to the change in size of the substituted amino acid residue. The present review deals with molecular basis of instability of 109 unstable hemoglobins reported to date and comprehensive hematological data has been presented on these variants in various tables for ready reference. Also an attempt has been made to classify these unstable hemoglobins according to their clinical manifestations. It will be noticed that many of the mutant exhibits a mild instability of the hemoglobin molecule but, there are examples in which the hemolytic process is severe and this can be directly correlated to a given substitution to its particular site or kind of amino acid substitution in the Hb molecule.

G. A. NIAZI, et al