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Structure and function of normal hemoglobins

Martin H Steinberg, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD


The structure and function of the normal human hemoglobins (ie, adult hemoglobin [hemoglobin A, HbA], hemoglobin A2 [HbA2], fetal hemoglobin [HbF], and the embryonic hemoglobins) will be discussed here, although fetal hemoglobin is discussed in greater detail separately. (See "Fetal hemoglobin (hemoglobin F) in health and disease".)

Abnormal hemoglobins are discussed separately. (See "Genetic disorders of hemoglobin oxygen affinity" and "Introduction to hemoglobin mutations" and "Unstable hemoglobin variants" and "Sickle hemoglobin polymer: Structure and functional properties".)


The study of hemoglobins, both normal and mutant, has provided fundamental insight into structure-function relationships of proteins in general and, in particular, the molecular basis of oxygen transport. The discovery that sickle hemoglobin has an abnormal electrophoretic mobility began the era of molecular medicine [1]. With the advent of recombinant DNA technology, research on hemoglobin provided early and important information about the organization and regulation of genes as well as insights as to how ontogeny affects gene expression [2].

Proteins with hemoglobin-like function (ie, hemoglobin motifs) can be found in the most ancient unicellular plants and animals and have evolved over hundreds of millions of years into gas transport proteins through the processes of gene duplication, conversion, divergence, and inactivating mutations [3]. In man, these processes have culminated in hemoglobin gene clusters on separate chromosomes (figure 1), whose expression is developmentally regulated [4]. (See 'Structure' below.)

All human hemoglobin genes contain three exons separated by two introns; the exons may encode distinct functional domains of the molecule. The tetrameric globular structure of hemoglobin is adapted to the physiology of complex organisms and their needs for regulation of oxygen delivery far better than the primitive globins hemocyanin or erythrocruorin, and single chain globins such as muscle myoglobin, cytoglobin, and neuroglobin.

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Literature review current through: Nov 2017. | This topic last updated: Sep 28, 2016.
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