3.5.1 Classification Based Upon Reaction Type

Introduction

Enzymes can be classified either on the basis of the reaction types that they catalyze or on the basis of the substrate which they act upon. The systematic nomenclature and classification of enzymes based on reaction types and reaction mechanism was given by the International Union of Biochemistry (in 1961). This is the most widely accepted system of enzyme classification.

Definition

Classification Based Upon Reaction Type: Enzymes are classified into six major groups based on the type of chemical reaction they catalyze. This system was developed by the International Union of Biochemistry (IUB) in 1961.

In simple words: Enzymes are grouped into six classes based on what type of reaction they carry out.

Core Concept

• Oxidoreductases
• Transferases
• Hydrolases
• Lyases
• Isomerases
• Ligases (Synthetases)

Detailed Explanation

1. Oxidoreductases

Definition: These enzymes catalyze oxidation/reduction of their substrate and act by removing or adding electrons or H⁺ ions from or to the substrate.

In simple words: Oxidoreductases catalyze oxidation-reduction reactions.

• They catalyze oxidation-reduction reactions.
• They remove or add electrons (e⁻) or hydrogen ions (H⁺).
• They are involved in energy metabolism.
• They often require coenzymes like NAD⁺, FAD, or NADP⁺.

Example: - Cytochrome oxidase oxidizes cytochrome. Cytochrome (reduced) Cytochrome oxidase→ Cytochrome (oxidized)

• Dehydrogenases
• Oxidases
• Reductases
• Peroxidases
• Catalases

2. Transferases

Definition: These enzymes catalyze the transfer of a specific functional group other than hydrogen from one substrate to another.

In simple words: Transferases transfer a functional group from one molecule to another.

• They transfer functional groups (e.g., phosphate, amino, methyl, acetyl).
• The chemical group transferred is not in a free state.
• They are involved in many metabolic pathways.

Example: - Hexokinase transfers a phosphate group from ATP to glucose. Glucose + ATP Hexokinase→ Glucose-6-phosphate + ADP

• Transaminases (transfer amino groups)
• Methyltransferases (transfer methyl groups)
• Acetyltransferases (transfer acetyl groups)
• Phosphorylases (transfer phosphate groups)

3. Hydrolases

Definition: These enzymes bring about the breakdown of large complex organic molecules into smaller ones by adding water (hydrolysis) and breaking the specific covalent bonds.

In simple words: Hydrolases break down large molecules into smaller ones by adding water.

• They catalyze hydrolysis reactions.
• They add water to break bonds.
• They are involved in digestion.
• They are essential for the breakdown of food molecules.

• Proteolytic enzymes – Breakdown proteins into peptones and peptides
• Pepsin
• Renin
• Trypsin
• Other digestive enzymes – Work in the digestive tract

• Lipases (break down lipids)
• Carbohydrases (break down carbohydrates)
• Nucleases (break down nucleic acids)
• Phosphatases (remove phosphate groups)

4. Lyases

Definition: These enzymes catalyze the breakdown of specific covalent bonds and removal of groups without hydrolysis.

In simple words: Lyases break bonds without using water.

• They break bonds without hydrolysis.
• They remove groups from substrates.
• They often form double bonds.
• They are involved in many metabolic reactions.

Example: - Histidine decarboxylase breaks the covalent bonds between carbon atoms in histidine forming carbon dioxide and histamine. Histidine Histidine decarboxylase→ Histamine + CO₂

• Decarboxylases (remove CO₂)
• Aldolases (break aldol bonds)
• Dehydratases (remove water)
• Deaminases (remove amino groups)

5. Isomerases

Definition: These enzymes bring about intra-molecular rearrangement of atoms in the molecules and thus forming one isomer from another.

In simple words: Isomerases convert one isomer into another.

• They catalyze intramolecular rearrangements.
• They convert one isomer into another.
• They do not change the molecular formula.
• They are involved in many metabolic pathways.

Example: - Phosphohexose isomerase changes glucose-6-phosphate to fructose-6-phosphate. Glucose-6-phosphate Phosphohexose isomerase→ Fructose-6-phosphate

• Epimerases (convert epimers)
• Racemases (convert D to L isomers)
• Mutases (transfer functional groups within a molecule)
• Cis-trans isomerases

6. Ligases (Synthetases)

Definition: These enzymes bring about joining together of two molecules. The energy is derived by hydrolysis of ATP.

In simple words: Ligases join two molecules together using energy from ATP.

• They join two molecules together.
• They require energy from ATP hydrolysis.
• They are involved in biosynthesis.
• They form new covalent bonds.

Example: - Polymerases are responsible for linking monomers into a polymer such as DNA or RNA. Nucleotide + Nucleotide DNA polymerase→ Dinucleotide + PPi

• DNA ligase (joins DNA fragments)
• RNA ligase (joins RNA fragments)
• Aminoacyl-tRNA synthetases (attach amino acids to tRNA)
• Carboxylases (add CO₂)

Summary Table of Enzyme Classification

Science Tidbits (from textbook)

How are enzymes named?

• Enzymes are named by adding "ase" to the name of substrate they act, e.g., proteases, lipases, etc.
• Enzymes are named according to the types of reaction they catalyze, e.g., oxidases, reductases, etc.
• Enzymes are named by taking into consideration both the substrate acted upon and the type of reaction catalyzed, e.g., DNA-polymerase.
• Some enzymes are named as per substance synthesized, e.g., rhodanese catalyzes synthesis of rhodonate from hydrochloric acid and sodium thiosulphate.

Intermediate Level

Classification in Detail

Sub-classes of Each Enzyme Class

Examples of Each Class

Enzyme Naming

Important Points

• 1. A systematic nomenclature and classification of enzymes based on reaction types and reaction mechanism was given by the International Union of Biochemistry (in 1961).
• 2. On that basis, all the enzymes have been classified into six groups:
• - Oxidoreductases
• - Transferases
• - Hydrolases
• - Lyases
• - Isomerases
• - Ligases
• 3. Oxidoreductases: These enzymes catalyze oxidation/reduction of their substrate and act by removing or adding electron or H⁺ ions from or to the substrate. For example, cytochrome oxidase oxidizes cytochrome.
• 4. Transferases: These enzymes catalyze the transfer of specific functional group other than hydrogen from one substrate to another. The chemical group transferred in the process is not in a free state, for example, hexokinase transfers a phosphate group from ATP to glucose.
• 5. Hydrolases: These enzymes bring about the breakdown of large complex organic molecules into smaller ones by adding water (hydrolysis) and breaking the specific covalent bonds. Examples are proteolytic enzymes which breakdown proteins into peptones and peptides such as pepsin, renin, and trypsin. Other digestive enzymes that work in digestive tract are also the examples of hydrolases.
• 6. Lyases: These enzymes catalyze the breakdown of specific covalent bonds and removal of groups without hydrolysis. For example, histidine decarboxylase breaks the covalent bonds between carbon atoms in histidine forming carbon dioxide and histamine.
• 7. Isomerases: These enzymes bring about intra-molecular rearrangement of atoms in the molecules and thus forming one isomer from another. For example, phosphohexose isomerase changes glucose-6-phosphate to fructose-6-phosphate.
• 8. Ligases (Synthetases): These enzymes bring about joining together of two molecules. The energy is derived by hydrolysis of ATP. For example, polymerases are responsible for linking monomers into a polymer such as DNA or RNA.
• 9. Science Tidbits: How are enzymes named?
• - Enzymes are named by adding "ase" to the name of substrate they act, e.g., proteases, lipases, etc.
• - Enzymes are named according to the types of reaction they catalyze, e.g., oxidases, reductases, etc.
• - Enzymes are named by taking into consideration both the substrate acted upon and the type of reaction catalyzed, e.g., DNA-polymerase.
• - Some enzymes are named as per substance synthesized, e.g., rhodanese catalyzes synthesis of rhodonate from hydrochloric acid and sodium thiosulphate.
• 10. Diagnostic uses of enzymes:
• - Aldolase: Progressive muscular dystrophy, viral hepatitis and advanced cancer of the prostate
• - Creatine Phosphokinase: Damage to muscle cells
• - Gamma-glutamyl Transpeptidase: In assessing liver function
• - Lactic Dehydrogenase: In differentiating heart attack, anemia, lung injury, or liver disease
• - Lipase: Damage to the pancreas
• 11. Venoms as enzyme inhibitors:
• - Snake venom is highly modified saliva that is produced by special glands of certain species of snakes.
• - Snake venom is a combination of many toxins (proteins) and different enzymes, use for the purposes like increasing the prey's uptake of toxins.
• - Snake venom inhibits cholinesterase to make the prey lose control of its muscles.
• - Venom is an inhibitor for an essential enzyme cytochrome oxidase in the cells.
• - Three distinct types of venom:
• 1. Hemotoxic venoms act on the heart and cardiovascular system.
• 2. Neurotoxic venom acts on the nervous system and brain.
• 3. Cytotoxic venom has a localized action at the site of the bite.
• - Venom occupies the active site of the enzyme or combining with the iron which may be present in the prosthetic group or which may be required as an enzyme activator.

Remember

• - Six classes of enzymes: Oxidoreductases, Transferases, Hydrolases, Lyases, Isomerases, Ligases
• - Oxidoreductases = oxidation-reduction; example: cytochrome oxidase
• - Transferases = transfer functional groups; example: hexokinase
• - Hydrolases = hydrolysis; example: pepsin, trypsin
• - Lyases = break bonds without hydrolysis; example: histidine decarboxylase
• - Isomerases = intramolecular rearrangement; example: phosphohexose isomerase
• - Ligases = join molecules with ATP; example: DNA polymerase
• - **IUB classification** = 1961
• - **EC numbers** = EC 1 to EC 6

Common Mistakes

• 1. Confusing the six classes – Each class catalyzes a different type of reaction.
• 2. Thinking hydrolases and lyases are the same – Hydrolases use water; Lyases do not use water.
• 3. Confusing transferases and ligases – Transferases transfer groups; Ligases join molecules with ATP.
• 4. Thinking oxidoreductases only remove electrons – They can also add electrons.
• 5. Confusing isomerases and lyases – Isomerases rearrange atoms; Lyases break bonds.
• 6. Forgetting the examples – Each class has specific examples.
• 7. Thinking all enzymes are hydrolases – Hydrolases are just one class.
• 8. Confusing the EC numbers – EC 1 = Oxidoreductases, EC 2 = Transferases, etc.
• 9. Thinking ligases do not require energy – Ligases require ATP.
• 10. Forgetting the IUB classification – The IUB classification was given in 1961.
• 11. Confusing the naming methods – Enzymes can be named after substrate, reaction, or both.
• 12. Thinking diagnostic enzymes are not important – Diagnostic enzymes are important in medicine.

Quick Revision

• A systematic nomenclature and classification of enzymes based on reaction types and reaction mechanism was given by International Union of Biochemistry (in 1961).
• On that basis all the enzymes have been classified into six groups:
• 1-Oxidoreductases: These enzymes catalyze oxidation/reduction of their substrate and act by removing or adding electron or H⁺ ions from or to the substrate. For example cytochrome oxidase oxidizes cytochrome.
• 2-Transferases: These enzymes catalyze the transfer of specific functional group other than hydrogen from one substrate to another. The chemical group transferred in the process is not in a free state, for example hexokinase transfers a phosphate group from ATP to glucose.
• 3-Hydrolases: These enzymes bring about the breakdown of large complex organic molecules into smaller ones by adding water (hydrolysis) and breaking the specific covalent bonds. Examples are proteolytic enzymes which breakdown proteins into peptones and peptides such as pepsin, renin and trypsin. Other digestive enzymes that work in digestive tract are also the examples of hydrolases.
• 4-Lyases: These enzymes catalyze the breakdown of specific covalent bonds and removal of groups without hydrolysis. For example histidine decarboxylase breaks the covalent bonds between carbon atoms in histidine forming carbon dioxide and histamine.
• 5-Isomerases: These enzymes bring about intra-molecular rearrangement of atoms in the molecules and thus forming one isomer from another. For example phosphohexose isomerase changes glucose 6-phosphate to fructose 6-phosphate.
• 6-Ligases (Synthetases): These enzymes bring about joining together of two molecules. The energy is derived by hydrolysis of ATP. For example polymerases are responsible for linking monomers into a polymer such as DNA or RNA.
• Science Tidbits: How are enzymes named?
• Enzymes are named by adding "ase" to the name of substrate they act, e.g., proteases, lipases etc.
• Enzymes are named according to the types of reaction they catalyse, e.g., oxidases, reductases etc.
• Enzymes are named by taking into consideration both the substrate acted upon and the type of reaction catalysed, e.g., DNA-polymerase.
• Some enzymes are named as per substance synthesized, e.g., rhodanese catalyses synthesis of rhodonate from hydrochloric acid and sodium thiosulphate.
• Diagnostic uses of enzymes:
• Aldolase: progressive muscular dystrophy, viral hepatitis and advanced cancer of the prostate
• Creatine Phosphokinase: damage to muscle cells
• Gamma-glutamyl Transpeptidase: in assessing liver function
• Lactic Dehydrogenase: in differentiating heart attack, anemia, lung injury, or liver disease
• Lipase: Damage to the pancreas
• Venoms as enzyme inhibitors:
• Snake venom is highly modified saliva that is produced by special glands of certain species of snakes.
• Snake venom is a combination of many toxins (proteins) and different enzymes, use for the purposes like increasing the prey's uptake of toxins.
• Snake venom inhibits cholinesterase to make the prey lose control of its muscles.
• Venom is an inhibitor for an essential enzyme cytochrome oxidase in the cells.
• There are three distinct type of venom that act on the body differently:
• Venom occupies the active site of the enzyme or combining with the iron which may present in the prosthetic group or which may be required as an enzyme activator.

60-Second Revision

• Six classes of enzymes: Oxidoreductases, Transferases, Hydrolases, Lyases, Isomerases, Ligases
• Oxidoreductases = oxidation-reduction; example: cytochrome oxidase
• Transferases = transfer functional groups; example: hexokinase
• Hydrolases = hydrolysis; example: pepsin, trypsin
• Lyases = break bonds without hydrolysis; example: histidine decarboxylase
• Isomerases = intramolecular rearrangement; example: phosphohexose isomerase
• Ligases = join molecules with ATP; example: DNA polymerase
• **IUB classification** = 1961
• **EC numbers** = EC 1 to EC 6
• Warning: Hydrolases use water; Lyases do not. Transferases transfer groups; Ligases join molecules with ATP. Each class has specific examples. The IUB classification was given in 1961. Enzymes can be named after substrate, reaction, or both. Diagnostic enzymes are important in medicine.