3.1 Enzyme Structure

Enzymes are biological catalysts, primarily globular proteins, that accelerate chemical reactions. Their function is critically dependent on their specific three-dimensional structure.

General Composition

Most enzymes are globular proteins made up of one or more polypeptide chains. The linear sequence of amino acids folds into a specific secondary and tertiary 3D structure, which is essential for its function. The exception to this is ribozymes, which are enzymes made of RNA rather than protein. A key example is peptidyl transferase, found in ribosomes, which forms peptide bonds during protein synthesis.

Ultrastructure of Animal and Plant Cells→

The Active Site

The catalytic activity of an enzyme is confined to a small, specific region called the active site. It is a three-dimensional, charge-bearing cavity formed by a small number of amino acids, typically 3 to 12. These amino acids may be far apart in the primary polypeptide chain but are brought close together by the protein's folding. The substrate binds to the active site via weak, non-covalent interactions such as hydrogen bonds and hydrophobic interactions.

The active site consists of two functional regions:

• Binding Site: Composed of amino acids that recognize and form temporary bonds with the substrate, holding it in the correct orientation.
• Catalytic Site: Composed of amino acids that carry out the chemical conversion of the substrate into the product.

Cofactors and Enzyme Activation

Some enzymes require a non-protein component called a cofactor to be catalytically active. The cofactor assists in binding the substrate and may participate directly in the catalytic process. The attachment of the cofactor helps establish the final, functional shape of the active site.

$\text{Apoenzyme}+\text{Cofactor}=\text{Holoenzyme (active)}$

An example of enzyme activation is pepsin. Pepsin is secreted in an inactive form called pepsinogen. An additional polypeptide fragment blocks its active site. In the acidic environment of the stomach (HCl), this fragment is removed, converting the inactive pepsinogen into active pepsin.

Types of Cofactors

Cofactors are broadly divided into three categories.

1. Inorganic Ions (Activators)

Detachable metallic ions such as $\mathrm{F}{\mathrm{e}}^{2+}$, $\mathrm{M}{\mathrm{g}}^{2+}$, $\mathrm{C}{\mathrm{u}}^{2+}$, and $\mathrm{Z}{\mathrm{n}}^{2+}$. They bind temporarily to the enzyme, often along with the substrate. The enzyme hexokinase requires $\mathrm{M}{\mathrm{g}}^{2+}$ to phosphorylate glucose:

$\text{Glucose}+\text{ATP}\underset{{\text{Mg}}^{2+}}{\overset{\text{Hexokinase}}{\to }}\text{Glucose-6-phosphate}+\text{ADP}$

2. Coenzymes

Detachable organic molecules, often derived from vitamins. They also bind temporarily to the enzyme during the reaction. Examples include ATP, $\mathrm{NA}{\mathrm{D}}^{+}$ (Nicotinamide adenine dinucleotide), and $\mathrm{FAD}$ (Flavin adenine dinucleotide). The enzyme alcohol dehydrogenase requires the coenzyme $\mathrm{NA}{\mathrm{D}}^{+}$:

$\text{Ethyl alcohol}\underset{\mathrm{NA}{\mathrm{D}}^{+}}{\overset{\text{Alcohol dehydrogenase}}{\to }}\text{Acetaldehyde}+\mathrm{NAD}{\mathrm{H}}_2$

3. Prosthetic Group

An organic molecule that is covalently and permanently bonded to the enzyme. It does not detach after the reaction is complete. The heme group, an iron-containing porphyrin ring, found in enzymes such as cytochromes is a classic example.