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4 - Disorders of hemoglobin synthesis

Thalassemias and structural hemoglobinopathies

from Section 1 - General and non-neoplastic hematopathology

Published online by Cambridge University Press:  03 May 2011

By
Alexander Kratz  and
Jeffrey Jhang
Edited by
Maria A. Proytcheva
Alexander Kratz
Affiliation:
Columbia University College of Physicians and Surgeons
Jeffrey Jhang
Affiliation:
Columbia University Medical Center
Maria A. Proytcheva
Affiliation:
Northwestern University Medical School, Illinois
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Summary

Normal hemoglobins

Structure and function of hemoglobin

Hemoglobin consists of two alpha-like and two beta-like globin chains which combine to form a tetramer. The globin tetramer is hydrophilic on its surface, making the molecule water soluble. The center is hydrophobic, stabilizing the heme ring and the iron molecule in the ferrous state (Fe2+). Located in the interior of each globin chain is a heme ring with an iron molecule in the center. It is in the heme ring that oxygen binding and release take place. In addition to oxygen transport, hemoglobin also plays a minor role in the transport of carbon dioxide, and as a scavenger of nitric oxide (NO).

As the partial pressure of oxygen is increased, hemoglobin becomes saturated with oxygen. The partial pressure at which 50% of hemoglobin is saturated is called the p50. Normal subjects have a p50 between 23 and 27 mmHg. Binding of an oxygen molecule in one heme changes the tetrameric structure so that additional oxygen molecules are bound with greater ease; this property of hemoglobin is called cooperativity, and is dependent on interactions between the globin chains (“heme–heme interaction”). The oxygen dissociation curve for hemoglobin A is sigmoid shaped because of this cooperativity (Fig. 4.1) [1, 2]. The sigmoid shape reflects how oxygen binding is favored at high oxygen tensions (lungs) and is rapidly released at low oxygen tensions (tissues).

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Diagnostic Pediatric Hematopathology , pp. 57 - 74
Publisher: Cambridge University Press
Print publication year: 2011

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