Hemoglobin Structure and Function

Hemoglobin Structure, Function, and Types

• Hemoglobin is a globular, transport, chromoprotein, and metalloprotein
• It is found within red blood cells and transports oxygen.

Hemoglobin Structure

• Composed of four polypeptide chains (globins) and four heme groups.
• Each globin chain comprises multiple amino acids arranged in a specific sequence (primary structure)
• The chains fold into a 3-D shape (tertiary structure), forming intricate helical structures (secondary structure).
• The four chains associate in a larger complex (quaternary structure).
• Alpha and beta are two types of globin chains.
• Alpha (a1 and a2) chains comprise 141 amino acids.
• Beta (b1 and b2) chains comprise 146 amino acids.
• Heme, a non-protein component, contains iron, crucial for oxygen binding.
• Heme has a porphyrin ring structure containing iron.
• The iron in heme can bind and release oxygen reversibly, facilitating oxygen transport.
• The globin chains are held together by non-covalent interactions.

Structural Levels of Hemoglobin

• Primary structure: The linear sequence of amino acids in each polypeptide chain.
• Secondary structure: The local folding of amino acid segments into α-helices.
• Tertiary structure: The overall 3-D folding of the polypeptide chain.
• Quaternary structure: The association of multiple polypeptide chains into a functional unit.

Structural Aspects

• Molecular weight of human hemoglobin is approximately 67,000 Daltons
• Normal male hemoglobin content: 14-16 g/dL
• Normal female hemoglobin content: 13-15 g/dL
• Normal hemoglobin (HbA) is primarily 97% HbA + 2% HbA2 +1%HbF
• HbA contains 2 alpha and 2 beta chains.
• Alpha chain: 141 amino acids.
• Beta chain: 146 amino acids.
• Hemoglobin F contains 2 alpha and 2 gamma chains.
• Subunits are held together by non-covalent bonds (polar, hydrophobic, and ionic interactions).

Quaternary Structure of Hemoglobin

• Hemoglobin tetramer is composed of two identical dimers, α₁β₁ and α₂β₂.
• The two globin chains within each dimer are tightly held together by inter-chain hydrophobic interactions.
• The two dimers are held together primarily by polar bonds, allowing some relative movement between the dimers.
• Weaker interactions between these mobile dimers result in differences in their relative positioning in Deoxyhemoglobin and Oxyhemoglobin

Helical Structure of Hemoglobin

• Hemoglobin has 8 helices (A through H).
• Heme is covalently bound to histidine at the F8 position in each globin chain.

Types of Globin Chains

• There are four globin chains (two alpha and two beta).
• The combination of these chains determines the type of hemoglobin.

Proximal and Distal Histidines

• Proximal (F8) and distal (E7) histidines are crucial for heme binding and oxygen transport.

Heme Structure

• Heme is a porphyrin ring complex containing iron.
• Iron in heme is ferrous (Fe²⁺).
• The porphyrin ring structure and associated organic components contribute to the red colour of hemoglobin.
• Heme is associated with hemoglobin, catalase, cytochrome, chlorophylls, Tryptophan pyrrolase.

T and R Forms of Hemoglobin

• T (taut) form: The deoxy form, with low oxygen affinity, stabilized by interactions between αβ dimers.
• R (relaxed) form: The oxy form, with high oxygen affinity, stabilized by interactions between αβ dimers.

Oxygenation of Hemoglobin

• Oxygen binding characteristics of hemoglobin change depending on allosteric modulators.
• Factors influencing oxygenation are: partial pressure of oxygen (PO2), pH, and 2,3-DPG (2,3-diphosphoglycerate)

Loading and Unloading of Oxygen

• The lower pH in tissues promotes O2 unloading and facilitates oxygen delivery to the tissues.
• In lungs, the process is reversed; oxygen is bound, protons are released, and combine with bicarbonate to form carbonic acid.

Iron within Hemoglobin (heme)

• Iron coordinates a molecule of oxygen.
• Iron coordinates to six atoms (4 planar and 2 in the middle)

Orientation of Iron

• In Deoxyhemoglobin (unbound oxygen), iron is displaced from the porphyrin plane

• In Oxyhemoglobin (bound oxygen), iron is coordinated planarity.

Functions of Hemoglobin

• Transports oxygen from lungs to tissues.
• Transports carbon dioxide and protons (H+) from tissues to the lungs.
• Acts as a buffer, maintaining proper pH levels.
• Found outside red blood cells in specific cells (e.g., dopaminergic neurons).
• Serves as an antioxidant and regulator of iron metabolism in varied tissues.

Non-Pathological Hemoglobin Variants

• Various forms of hemoglobin exist during embryonic and fetal development and adulthood.
• Gower 1, Gower 2, Hemoglobin F, Portland, Hemoglobin A.
• Hemoglobin A is the most prevalent form.

Explore the intricate structure and vital functions of hemoglobin in this informative quiz. Learn about the composition of polypeptide chains, heme groups, and how they work together to transport oxygen in the bloodstream. Test your knowledge on the types of globin chains and their roles!