Structural Biochemistry/Protein function/Heme group/Biological Roles of Metal Ions

Overview

Metal ions play an important role in biochemical processes. Because metal ions are positively charged ions that are stable in multiple oxidation states and can form strong yet conformationally changeable bonds, they become attractive catalytic substances.

Many biochemical reactions depend on the presence of metal ions, which are a part of coordination complexes. Those metal ions function to facilitate or inhibit biochemical reactions in the solution.

In Trigger and Control Mechanisms

Ions, such as Na⁺, K⁺, Ca²⁺, function as charge carriers. Because membrane ion pumps maintain a concentration gradients of those ions from the inside to the outside of the membrane, the movement of the ions would trigger mechanisms. The changes in concentration gradients are signals for nerve and muscle actions. These ions typically are used via intracellular and extracellular concentration differences to create a electric potential gradient. In doing so, ion channels can be controlled via a variety of chemical mechanisms. However, they are not responsible for conformational changes, but instead can cause a cascade of protein activation.

Na⁺
1. regulation of body fluids, including blood plasma, extracellular fluids in tissues
2. signal transduction in nerves and muscles
3. transmission of heat
4. transportation of nutrients and wastes

K⁺
1. trigger taste sensations
2. polarization of membrane: muscle contraction, transmission of nerve impulses
3. regulation of body fluids, including cell fluid, plasma

Ca²⁺
1. trigger for muscle contraction, neurotransmitter release
2. cancer prevention candidate

Catalytic Influences

Metal ions are able to promote reactions by providing appropriate geometry for bond breaking and bond formation. Many coordination sites in the molecules are tetrahedral, octahedral, or square-planar, but metal ions also provide other geometric variation, which enables reactions to take place. Metal ions, transition metals especially, are frequently utilized as a catalyzing group due to their extended octet. They are therefore able to create multiple interactions as well as ionization states that facilitate conformational changes to the protein. Furthermore, they are able to create coordination complexes with ligands, which are considerably weaker bonds than covalent and ionic bonds, but allow for ligand stabilization.

These metal ions participate in catalytic mechanisms in 3 main ways:

1. Binding to substrates to orient them properly for catalytic reaction.

2. Mediation oxidationo-reduction reactions via reversible changes in oxidation state of the central metal ion.

3. Electrostatically stabilizing or shielding negative charges.

Essentially, metal ions serve as a electron sink, much as protonation does. However, metal ions can be in high concentration without an effect on pH. For example, carbonic anhydrase facilitates the creation of carboxylate ion from water and carbon dioxide. It is initiated by the coordination bonding of OH^- to Zn²⁺. This stabilizes the negative charge on the oxygen and facilitates a nucleophilic attack on the carbon atom in carbon dioxide.

Some examples of metal ions used in catalytic reactions include include Fe²⁺, Fe³⁺, Cu²⁺, Mn²⁺, and Co²⁺.

Lewis Acid Behavior

Binding to a metal ion makes water molecule more acidic than free water molecule. Coordination to proteins enhances the effect even more, resulting in M-OH species that is able to further react with other biological substances. Mg²⁺ can activate phosphotransferases and phosphokinase, while Zn²⁺ and Ca²⁺ are able to catalyze hydrolysis of phosphates, serving as Lewis acids.

File:Active Site in Carboxypeptidzase A.jpg

Uncatalyzed hydrolysis rate constant is about ~10^-11 s^-1, while with enzyme catalyzing the reaction, reaction rate constant increases to k = ~10⁴ s^-1.

Carboxypeptidzase A has 307 amino acid residues. One Zn²⁺ ion is cleft on one side.

- Molecular weight = 34600 g/mol

- Egg-shaped

- Dimension: 50*38A

- Carboxypeptidase catalyzes the hydrolysis of c-terminal amino acid residues of the protein. It is released in pancreatic juice of animals for the digestion of proteins.

File:Carboxypeptidase.gif

Interaction with Small Molecules

Bending with small molecules enables metal ions to adopt unusual angles, bond distances, or specific geometry, and hence increases their reactivity. In hemoglobin and myoglobin, ferric ion is able to bind to oxygen, serving as a oxygen storage and transport. Oxygen molecules that bind to Iron metal ions is accompanied by the partial transfer of an electron from the metal ion to the oxygen. Their structure is best seen as a complex formed between ferric ion and a superoxide anion. Which is important than the heme-group stabilizes this binding or else superoxide is released into the body which could be biologically dangerous. Iron stabilizes this conformation in a strong ionic interaction which prevents this superoxide oxygen anion from leaving out of the blood cell.

File:Superoxide.gif

Oxidation-Reduction Reactions and Catalysis

Coordination by different ligands changes the reduction-oxidation potentials of a reaction, making it easier or, sometimes, more difficult to take place. The change in redox potential also enables electron transfer.

1. The reaction of O₂ -> H₂O is catalyzed by Fe²⁺, where Fe²⁺ -> Fe³⁺.

Similarly, N₂ is oxidized to flux NH₃O while Cu⁺ is reduced to Cu²⁺.

2. The reverse reaction mentioned above, H₂O -> O₂ is catalyzed by the valence charge of Mn.

3. Ribose is reduced to deoxyribose, a reaction catalyzed by Co⁺, where Co⁺ is oxidized to Co³⁺.