Structural Biochemistry/Enzyme/Mechanisms

Types of Catalysis
Enzymes are proteins that catalyze a reaction by stabilizing the transition state and therefore, lowering the activation energy of the reaction. To achieve this, enzymes use different classes of reactions or catalytic strategies. The strategies used to catalyze a reaction are:

Covalent Catalysis

In this type of reaction, a nucleophile in the active site reacts with a reactive group in the substrate. The nucleophile is temporarily, covalently bonded to a substrate during catalysis.

Example: Chymotrypsin uses a strong nucleophile to attack a normally unreactive carbonyl carbon atom of a substrate. The nucleophile is briefly covalently attached to the substrate in catalysis.

Acid-Base Reactions

In this type of reaction a molecule other than water acts as a proton acceptor or donor.

Example: In the catalytic triad, the histidine residue polarizes the hydroxyl group on serine so that it is ready for deprotonation. When a substrate is present, it takes the proton from hydroxyl group of serine which makes the residue act like a base catalyst.

Catalysis by Approximation

In this type of reaction, two subtrates are positioned together on a single binding surface so that the formation of the new bond is easier, speeding up the reaction.

Example: NMP has a phosphoryl group transferred from ATP by an enzyme holding its two substrates together and aligning them to stabilize the transition state.

Metal Ion Catalysis

In this type of reaction, metal ions help the formation of nucleotides or the ion acts as an electrophile to stabilize a negative charge on an intermediate.

Example: Carbonic Anhydrase is an enzyme that contains a zinc ion which aids in turning water into a better nucleophile. The formation of a hydroxide ion speeds up the nucleophilic attack of CO2.

The type of strategy that is employed is based on the enzyme's structural properties and the reaction that the enzyme will catalyze. Many times a combination of strategies is used to in catalytic reactions.

Ping-Pong Mechanism
Ping pong reactions, or double displacement reactions, involve the release of one or more products before all of the substrates bind to the enzyme. This back and forth is where the reactions get the name ping-pong. A defining part of a ping-pong reaction is called the substituted enzyme intermediate, which has a temporarily modified enzyme that shuttles groups back and forth. An example of a double displacement reaction is as follows:

Aspartate + alpha-Ketoglutarate <-(with enzyme aminotransferase)-> Oxaloacetate + Glutamate

Though this reaction seems like a normal reaction with two reactants and two products, the order of events is what defines the reaction. First, aspartate binds to the enzyme. Then, (before alpha-Ketoglutarate binds), oxaloacetate is released. Now, alpha-Ketoglutarate binds to the enzyme-substrate complex. Last of all, these substrates react and glutamate is released and the enzyme reforms.

Sequential Reactions
This is a more orthodox description of an enzymatic reaction. Sequential reactions require all of the substrates to bind to the enzyme before all of the products are released. These can be further broken down into ordered and random sequential reactions. Ordered reactions have a specific order for which substrates must bind to the enzyme, whereas random reactions do not.

An example of an ordered reaction is as follows:

Pyruvate + NADH <-(lactate dehydrogenase)-> lactate + NAD+

In this reaction, the pyruvate must first bind to the enzyme before the NADH may react with it. Then, lactate is released first before NAD+ is released.

An example of a random reaction is as follows:

Creatine + ATP <-(creatine kinase)-> Phosphocreatine + ADP

In this reaction, the enzyme is not selective, and either Creatine or ATP can bind first. Similarly, either Phosphocreatine or ADP can be released first.