# Structural Biochemistry/Catalytic Strategies/Metal Ion Catalysis
## Overview

Metal ion catalysis, or electrostatic catalysis, is a specific mechanism that utilizes metalloenzymes with tightly bound metal ions such as Fe$^{2+}$, Cu$^{2+}$, Zn$^{2+}$, Mn$^{2+}$, Co$^{3+}$, Ni$^{3+}$, Mo$^{6+}$ (the first three being the most commonly used) to carry out a catalytic reaction. This area of catalysis also includes metal ions which are not tightly bound to a metalloenzyme, such as Na$^+$, K$^+$, Mg$^{2+}$, Ca$^{2+}$.
Enzymes can catalyze a reaction by the use of metals. Metals often facilitate the catalytic process in different ways. The metals can either assist in the catalytic reaction, activate the enzyme to begin the catalysis or they can inhibit reactions in solution. Metals activate the enzyme by changing its shape but are not actually involved in the catalytic reaction.
First, the metal can make it easier to form a nucleophile which is the case of carbonic anhydrase and other enzymes. In this case, the metal facilitates the release of a proton from a bound water to produce a nucleophilic hydroxide ion and start the catalytic reaction. With the polarization of the O-H bond, the acidity of the bound water can increase. Equally important, the metal can promote the production of an electophile which in turn stabilizes negative charge on the intermediate. Also, metals can promote binding of the enzyme and substrate by acting as a bridge to increase the binding energy and orient them correctly to make the reaction possible.
Common metals that take part in metal ion catalysts are copper ion and zinc ion. The catalysis of carboxypeptidase A is a prime example of this catalytic strategy. The iron metal ion is also very common--from the binding of oxygen to hemoglobin and myoglobin, to participating as an electron carrier in the cytochromes of the electron transport chain, to even as a detoxifying agent in catalase and peroxidase.
Metal ions also have the ability to stabilize transition states, which makes them very useful in catalytic chemistry because it allows them to stabilize unstable intermediates that are still transitioning into a structure that's going to allow them to react with another substrate and form the final product. For example, in the presence of a tetrahedral oxyanion and another oxygen that is attached to a carbonyl functional group nearby that is also about to become nucleophilic as an intermediate, the metal ion can coordinate to these two neighboring anions and participate in charge stabilization.
Forming this Copper 2+ metal ion bridge allows both nucleophilic/anionic oxygens to be stabilized at the same time. It also positions this molecule in the appropriate geometry for breaking or forming bonds. Metal ions like these enable species to acquire a reactive role by coercing them to adopt unusual angles and bond distances.
Metal ions that are not tightly bound to a metalloenzyme, such as Na$^+$ and K$^+$ mentioned earlier participate as specific charge carriers in the membrane of our cells. For example, Na$^+$ and K$^+$ control the membrane's electrostatic voltage. They are ions that conduct the inside of our membrane's to have a net negative charge by the use of ion pumps and concentration gradients. Ca$^{2+}$ is also an important metal ion that controls and regulates the passing of neurotransmitters from one axon to the next in order to sound out signals throughout the body.