Enzymes

Enzymes are proteins that speed up the metabolic process in the body. All the functions require energy to perform in the human body. Energy comes from chemical reactions that happen inside each cell of the body. In each cell, mitochondria are the powerhouse that generates power from these chemical reactions. There are lots of chemical reactions that happen in our body and these reactions, catalysts are useful to make these reactions many folds faster in comparison to the normal reaction without catalyst. Enzymes are such biological catalysts or biocatalysts which make some impossible reactions possible in the human body. Enzymes help to initiate lots of reactions and give support to body functions like digesting food, muscle and nerve functions and many others.

Depending on their functionalities, there are many types of enzymes found in the human body.  Enzymes react on substrates and convert these substrates into products.

Classification and Nomenclature of Enzymes

There are different types of classification of enzymes based on their activity and amino acid sequence similarity. The classification of enzymes is based on different ways like recommended names, types of reaction, EC numbers and systematic names. In the systematic name classification, an attempt has been to make an unambiguous name of the enzyme based on the reaction that it catalyses. There are several genetic words related to the type of the reaction and these genetic words ending with “–ase” describe the name of the enzyme in systematic names and recommended names classification.

Based on some typical reactions these names are oxygenase, racemase, epimerase etc. EC number is one of the accepted terminologies to address enzymes. This is a four-digit number that identifies the enzyme by the reaction it catalyses. Nomenclature of enzymes in terms of EC numbers are developed by IUBMB (International Union of Biochemistry and Molecular Biology). The top-level classification of EC numbers is as below:

1. EC 1, Oxidoreductases: Enzyme catalyses oxidation and reduction reactions
2. EC 2, Transferases: Enzyme transfers a functional group
3. EC 3, Hydrolases: Enzyme catalyses the hydrolysis of various bonds
4. EC 4, Lyases: Enzyme cleaves various bonds by means other than hydrolysis and oxidation
5. EC 5, Isomerases: Enzyme catalyses isomerizing process in a single molecule
6. EC 6, Ligases: Enzyme catalyses the reaction which joins two molecules with covalent bonds
7. EC 7, Translocases: Enzyme catalyses the movements of ions and molecules across or within the membranes.

These are further subdivided depending upon the substrate, products and chemical mechanisms. These EC numbers do not reflect the sequence of the reaction. For example, two ligases with the same EC numbers can have different sequences even if they are catalysing the same reaction. Hexokinase enzyme with EC number EC2.7.1.1 is a transferase that adds a phosphate group to a hexose sugar, a molecule containing an alcohol group.

Cofactors 

Most of the metabolic processes happen in the cell where enzymes are very much required to make reaction rates of these processes fast enough to produce products in less time. In some cases, there is no need for additional components by enzymes to show full activity and they are alone sufficient to catalyse the reaction and convert the substrate into products. In some cases, enzymes need non-protein molecules to complete the catalytic reactions. These non-protein molecules, called cofactors, are either inorganic like iron or zinc ions, or organic molecules like vitamins or vitamin-derived molecules that do not bind with the enzyme. These cofactors are attached near the substrate-binding site that facilitates the substrate to bind with the enzyme.

Depending on the binding between cofactors and enzymes, they are of two types, namely, prosthetic groups and coenzymes. The prosthetic groups are tightly bound with the enzymes and do not get modified during the catalytic reaction whereas coenzymes are loosely binding with the enzymes and can modify themselves during the enzymatic reaction. Without cofactors, these enzymes are inactive and are termed apoenzymes or apoproteins. Once they bind with cofactors, they become holoenzymes or haloenzymes.

Coenzymes

Coenzymes are the organic attachments to enzymes that are loosely attached to enzymes and can modify during the catalytic reaction. They transport an organic or chemical group from one enzyme to another. Like enzymes, coenzymes can be reused numerous times and can become free once the catalytic reaction completes. Since coenzymes cannot be synthesized in the body they are extracted or acquired from closely related compounds like vitamins that are present in the diet. Though coenzymes and cofactors help the enzymes to carry out the chemical reactions they alone are not able to carry out the reactions.

Inhibition of Enzymes

In the human body, there are some chemical reactions, induced and catalysed by enzymes, which harm the normal functioning of the body. For example, fever, cold, cancer, fungal or bacterial infections etc. These diseases need curing before they harm the body. Enzyme inhibitors are useful for this purpose because they are the molecules that bind to the active sites of enzymes and decrease their activity. Due to the decrease in the activity of enzymes, enzyme-substrate formation suppresses and consequently prevents product formation. So it can be said that the enzyme activity is inversely proportional to the concentration of enzyme inhibitors.

More broadly, inhibitors are classified into two categories, reversible and irreversible. Reversible inhibitors attached to enzymes are those that form non-covalent bonds like ionic, hydrogen bonds or hydrophobic interactions, to the active sites of the substrate and deactivate or slow down the chemical reaction. For example, the drug methotrexate (used to treat some kind of cancer) stops the formation of new affected cells and once the use of the drug (after cure) is stopped the production of new healthy cells starts. Irreversible inhibitors are those that form covalent bonds with the enzyme and permanently inactivate the enzyme. Drugs like penicillin and aspirin are used as irreversible inhibitors.

Frequently Asked Questions on Enzymes

Q.1: How many types of reversible inhibitors are available?

Answer: There are four types of reversible inhibitors are available and they are competitive, non-competitive, uncompetitive and mixed inhibitors. The competitive inhibitors resemble the real substrate of the enzyme. The non-competitive inhibitors bind with enzymes on the site other than where the substrate binds. Though the activity of the enzyme is not affected its catalytic efficiency reduces. The uncompetitive inhibitors bind only with the enzyme-substrate complex and make this complex inactive. This is effective when the concentration of substrate is high enough. Mixed inhibitors bind with the enzyme at the same time as the substrate. This type of binding affects the enzyme-substrate binding. Though this situation can be reduced by increasing the substrate concentration it cannot be overcome.

Q.2:  Give three examples of cofactors that come from vitamins.

Answer: Cofactors are non-protein molecules that are required by the enzyme to act as an enzyme. These non-protein molecules are vitamins or vitamin-derived molecules. Vision, blood clotting and hormone production are some processes that require vitamin-based cofactors. These cofactors are:

• The retinal cofactor is required by enzyme opsins present in the eye and is responsible for vision. A retinal cofactor is the aldehyde version of vitamin A.
• Thiamin pyrophosphate, a cofactor, is derived from vitamin B1. This is a cofactor in the enzyme that is responsible for oxidative decarboxylation and transketolase catalytic reaction.
• Hydroxylase, an enzyme, catalyses the hydroxylation process of proline and lysine. It needs ascorbic acid, derived from vitamin C, as a cofactor.

Q.3: Which cofactor is responsible for bone remodelling and blood clotting?

Answer: Vitamin K, as a cofactor is required by gamma-carboxylases enzyme that catalyses the formation of proteins, osteocalcin and prothrombin, which are responsible for bone remodelling and blood clotting respectively.