Structure of Hemoglobin

     Hemoglobin is the life-giving substance of every red blood cell, the oxygen-carrying component of the red blood cell. Each red blood cell is nothing more than a fluid-filled sac, with the fluid being hemoglobin. Every organ in the human body depends on oxygenation for growth and function, and this process is ultimately controlled by hemoglobin. In 4 months (120 days), red blood cells with normal hemoglobin content submit to the rigors of circulation. Red blood cells are stretched, twisted, pummeled, and squeezed as they make their way through the circulatory watershed.

The hemoglobin molecule consists of two primary structures:

1- Heme

This structure involves four iron atoms in the ferrous state (Fe²⁺ ), because iron in the ferric state (Fe³⁺ ) cannot bind oxygen, surrounded by protoporphyrin IX, or the porphyrin ring, a structure formed in the nucleated red blood cells. Protoporphyrin IX is the final product in the synthesis of the heme molecule. It results from the interaction of succinyl coenzyme A and delta-aminolevulinic acid in the mitochondria of the nucleated red blood cells. Several intermediate by-products are formed, including porphobilinogen, uroporphyrinogen, and coproporphyrin. When iron is incorporated, it combines with protoporphyrin to form the complete heme molecule. Defects in any of the intermediate products can impair hemoglobin function.
2- Globin

This structure consists of amino acids linked together to form a polypeptide chain, a bracelet of amino acids. The most predominant chains for adult hemoglobins are the alpha and beta chains. Alpha chains have 141 amino acids in a unique arrangement, and beta chains have 146 amino acids in a unique arrangement. The heme and globin portions of the hemoglobin molecule are linked together by chemical bonds.

2,3-Diphosphoglycerate (2,3-DPG)

2,3-DPG is a substance produced via the Embden-Meyerhof pathway during anaerobic glycolysis. This structure is intimately related to oxygen affinity of hemoglobin. As 2,3-DPG increased, the affinity of hemoglobin to oxygen is decreased. 

     Each hemoglobin molecule consists of four heme molecules with iron at the center and two pairs of globin chains. The heme structure sits lodged in the pocket of the globin chains. Hemoglobin begins to be synthesized at the polychromatic normoblast stage of red blood cell development. This synthesis is visualized by the change in cytoplasmic color from a deep blue to a lavender-tinged cytoplasmic color. Of hemoglobin, 65% is synthesized before the red blood cell nucleus is extruded, with an additional 35% synthesized by the reticulocyte stage. Normal mature red blood cells have a full complement of hemoglobin, which occupies a little less than one-half of the surface area of the red blood cell.

Figure: Hemoglobin molecule: note four heme molecules tucked inside globin chains.