Chapter 5: Protein Function

Oxygen-Binding Proteins (Section 5.1)

This section explores the structure and function of proteins that bind oxygen, focusing on myoglobin and hemoglobin. These proteins are essential for oxygen transport and storage in biological systems, and their function is closely related to their structure and binding properties.

Oxygen-Binding Proteins

Myoglobin and Hemoglobin: Structure and Function

• Myoglobin is a monomeric protein found primarily in muscle tissue, where it serves as an oxygen storage molecule.

• Hemoglobin is a tetrameric protein found in red blood cells, responsible for transporting oxygen from the lungs to tissues and facilitating the return transport of carbon dioxide.

• Both proteins contain a heme group, which is the site of oxygen binding.

Heme Group Structure

• The heme group consists of a porphyrin ring coordinated to an iron (Fe2+) ion.

• The iron ion forms coordinate covalent bonds with the nitrogen atoms of the porphyrin ring and can also bind oxygen.

• In hemoglobin and myoglobin, the iron is also coordinated to a histidine residue from the protein (proximal histidine).

• Coordinate covalent bond: A type of covalent bond in which both electrons in the bond originate from the same atom (often seen in metal-ligand complexes).

Example: The imidazole side chain of a histidine residue donates a pair of electrons to the iron ion in the heme group, forming a coordinate covalent bond.

Comparison of Myoglobin and Hemoglobin

• Myoglobin has a single polypeptide chain and one heme group; it binds oxygen with high affinity and is not cooperative.

• Hemoglobin consists of four subunits (two alpha and two beta chains), each with its own heme group; it exhibits cooperative binding of oxygen.

• Cooperative binding means that the binding of oxygen to one subunit increases the affinity of the remaining subunits for oxygen.

Oxygen Binding: Equilibrium and Dissociation Constant

• The binding of a ligand (L, such as O2) to a protein (P) can be described by the equilibrium:

• The dissociation constant () is defined as:

• A lower indicates higher affinity of the protein for the ligand.

• The binding curve of myoglobin is hyperbolic, while hemoglobin's is sigmoidal due to cooperativity.

Regulation of Oxygen Binding

The Bohr Effect

The Bohr effect describes how changes in pH and CO2 concentration affect hemoglobin's oxygen affinity.

• Actively metabolizing tissues generate H+, lowering the pH and promoting the release of O2 from hemoglobin.

• Protons bind to specific histidine residues (e.g., His146), stabilizing the T (tense) state of hemoglobin and facilitating O2 release.

• This effect increases the efficiency of oxygen delivery to tissues where it is most needed.

CO2 Transport and Carbamate Formation

• CO2 produced by metabolism is exported from tissues in several forms:

  • As a carbamate attached to the N-terminus of hemoglobin subunits:

• Carbamate formation also produces a proton, contributing to the Bohr effect.

• Carbamate groups form additional salt bridges, further stabilizing the T state of hemoglobin.

• Most CO2 is exported as dissolved bicarbonate, formed by the enzyme carbonic anhydrase, which also produces a proton.

2,3-Bisphosphoglycerate (2,3-BPG) Regulation

• 2,3-Bisphosphoglycerate (2,3-BPG) is a negative heterotropic regulator of hemoglobin function.

• It is present at millimolar concentrations in erythrocytes and is produced from an intermediate in glycolysis.

• 2,3-BPG is a small, highly negatively charged molecule that binds in the central cavity of hemoglobin, stabilizing the T state and reducing oxygen affinity.

• This regulation ensures efficient oxygen release in tissues.

Summary Table: Comparison of Myoglobin and Hemoglobin

Additional info: The notes include diagrams of the heme group, the coordination of iron, and structural comparisons between myoglobin and hemoglobin. The Bohr effect and 2,3-BPG are key physiological regulators of hemoglobin's oxygen affinity, ensuring efficient oxygen delivery and CO2 removal in response to tissue metabolic activity.