BIOCHEMISTRY - L. Stryer - 1984

VOLUME 1

PART I. CONFORMATION AND DYNAMICS

CHAPTER 3. OXYGEN CARRIERS: MYOGLOBIN AND HEMOGLOBIN

Summary

Myoglobin and Hemoglobin are Proteins that function as oxygen carriers in vertebrates. Myoglobin facilitates oxygen diffusion in Muscle tissue and provides a local reserve of oxygen. Hemoglobin, contained within erythrocytes, serves as the primary oxygen carrier in the Blood. The capacity of these proteins to bind oxygen is due to the presence of a tightly bound prosthetic group, heme, within their molecular Structure. Heme is a substituted porphyrin with a centrally coordinated iron atom. The iron in heme can exist in the ferrous (+2) or ferric (+3) oxidation state. Only the ferrous form is capable of binding O₂.

Myoglobin consists of a single polypeptide chain of 153 amino acid residues (17.8 kDa) folded into a compact globular structure. The interior of the molecule is formed almost exclusively by nonpolar residues, whereas both polar and nonpolar residues are located On the surface. Approximately 75% of the polypeptide chain is arranged in $\alpha$-helices, comprising eight helical segments. The single ferrous heme group is nestled within a hydrophobic pocket, which protects it from oxidation to the ferric state. The iron atom of the heme is directly coordinated to a nitrogen atom of a Histidine side chain. This proximal histidine (F8) occupies the fifth coordination position. The sixth coordination position, on the opposite side of the heme plane, serves as the O₂ binding site. A second histidine, designated as the distal histidine (E7), is located in close proximity to this site. The proximal histidine enhances the oxygen affinity of the heme, while the distal histidine exerts a steric effect that reduces carbon monoxide binding. Furthermore, the distal histidine and other surrounding amino acid residues suppress The oxidation of heme to the ferric form.

Functionally active myoglobin can be reconstituted from a mixture of denatured (unfolded) apomyoglobin and heme. This refolding experiment demonstrates that the native conformation of myoglobin is predetermined by its Amino Acid Sequence; a analogous phenomenon was first established for Ribonuclease. The clustering of nonpolar amino acid residues in the interior of the myoglobin molecule provides the hydrophobic driving force necessary for The formation of its compact folded structure.

Hemoglobin is a tetrameric protein composed of four polypeptide chains, each containing a heme group. Adult hemoglobin A, the major hemoglobin in adults, has an $\alpha_2\beta_2$ subunit structure. Hemoglobin A₂, a minor adult hemoglobin, has the composition $\alpha_2\delta_2$, whereas fetal hemoglobin F consists of $\alpha_2\gamma_2$. Three-dimensional structures

The three-dimensional structures of the $\alpha$- and $\beta$-chains of hemoglobin bear a striking resemblance to that of myoglobin, despite significant differences in their Amino acid sequences. Comparisons of amino acid sequences across numerous animal species reveal that the positions of nine Amino Acids remain virtually invariant. This group of conserved residues includes several located near the heme group, notably the proximal and distal histidines. Another conserved feature is the pronounced Hydrophobicity of the interior of each subunit.