Iron and Copper Roles in Biological Oxygen Transport

Hemoglobin Iron Environment and Geometry

The iron ion (Fe) in Hemoglobin (Hb) is in a square planar environment, bonded to four nitrogen (N) atoms of the porphyrin ring. The fifth coordination position is bound to a nitrogen atom from a histidine residue (perpendicular to the plane), and the sixth position binds O₂ in oxyhemoglobin. When oxygenated, the coordination geometry around the iron is essentially octahedral. In contrast, deoxygenated Hb has a five-coordinate, square pyramidal geometry, as the sixth position is vacant.

Role of Magnesium and Calcium Competition

Magnesium (Mg) is extremely important. It plays a role related to the Na⁺/K⁺ pump; the interior of the cell requires large amounts of K⁺ and low amounts of Na⁺. Mg facilitates the transport of K⁺ inward and Na⁺ outward. It is crucial for utilizing and transferring intracellular phosphate (e.g., in ATP hydrolysis). Additionally, Mg regulates intracellular calcium [Ca²⁺] levels. Therefore, when the magnesium concentration [Mg²⁺] is low, it can lead to an excess of intracellular [Ca²⁺], which may cause muscle cramps.

Hemocyanin Copper Center Characteristics

Hemocyanin contains copper (Cu) centers. When in the deoxygenated (deoxy) state, the copper is in the Cu(I) oxidation state. When it binds oxygen (oxy state), the copper is oxidized to Cu(II). The coordination geometry around the copper centers changes upon oxygenation; the text mentions trigonal bipyramidal, although the structure typically involves two copper ions bridging an O₂ molecule.

Plastocyanin: Distorted Tetrahedral Copper Center

This metalloprotein features a copper center that does not adopt a perfect tetrahedral or square planar geometry but rather a distorted structure between these two. This distortion is functionally important because plastocyanin acts as an electron transfer catalyst, cycling its metal center between Cu(I) and Cu(II) states. The distorted geometry lowers the reorganization energy required for this redox change, facilitating rapid electron transfer without high energy expenditure, as the structure is intermediate between the preferred geometries of Cu(I) (tetrahedral) and Cu(II) (square planar). The oxidized Cu(II) form of plastocyanin is characteristically blue.

Essential Metals in Biological Systems

An essential metal is one that is critically important for a biological process, for example, in transporting O₂ (like iron in Hb) or in catalyzing a metabolic reaction. Its absence leads to a functional alteration and subsequent illness. However, even essential metals can cause disease when present in excess, as these metals are typically required only in low concentrations.

The Cooperative Effect in Hemoglobin

Cooperativity in Hemoglobin (Hb) means that when one oxygen molecule (O₂) binds to one subunit of Hb, the affinity of the remaining subunits for O₂ increases, making it easier for them to bind O₂ as well. Conversely, when one O₂ molecule dissociates, the dissociation of O₂ from the other subunits is also facilitated.

Hb + O2 <=> Hb(O2)
Hb(O2) + O2 <=> Hb(O2)2
...
etc.

Dioxygen Binding to Hemoglobin: MO Theory

According to molecular orbital theory, the ground state of the dioxygen molecule (O₂) is paramagnetic, existing in a triplet state (with two unpaired electrons in degenerate π* orbitals). When oxygen binds to the iron of Hb, the binding geometry is angular. This binding is thought to involve a change in the electronic state of O₂ from triplet to a singlet-like state upon coordination, meaning the electrons become paired within the Fe-O₂ unit. Overcoming the energy barrier associated with this spin state change (reported here as 23 kcal/mol) is part of the activation energy for oxygen binding.

Ferredoxin Iron-Sulfur Clusters

Ferredoxins are proteins containing iron-sulfur (Fe-S) clusters involved in electron transfer. Common types include:

• [2Fe-2S] clusters: Two iron atoms tetrahedrally coordinated by two bridging sulfide ions and four cysteine residues.
• [4Fe-4S] clusters: Four iron atoms and four sulfide ions arranged in a cubane-like structure, with each iron typically coordinated by a cysteine residue.
• [3Fe-4S] clusters: A cubane-like structure with one iron vertex missing.

Cytochrome Classification and Properties

Cytochromes are heme-containing proteins primarily involved in electron transport chains. They are often classified based on the position of the alpha peak in their visible absorption spectrum in the reduced state:

• Cytochrome c: Alpha peak around 548-552 nm.
• Cytochrome b: Alpha peak around 555-560 nm.
• (Note: Cytochrome a typically absorbs around 600-605 nm, not 570 nm as perhaps implied).

Some cytochromes have the 6th coordination site of the heme iron blocked (e.g., by a methionine residue in cytochrome c), preventing them from binding external ligands like O₂ and making them suitable for electron transport rather than oxygen transport.