ENZYMES

CHEM 102 Learning Objectives

• Explain the role of enzymes in biological systems.
• Categorize enzymes based on reactions they catalyze.
• Explain different factors that can affect enzyme activity.
• Explain the mechanisms as to how enzymes can catalyze biochemical reactions.
• Describe inhibition and regulation of enzymes.

General Characteristics of Enzymes

• Catalysis: One of the most important processes in the human body, speeding up chemical reactions with a catalyst.
• Catalysts: Not consumed during a reaction, but help the reaction occur more rapidly.
• Enzymes: Biological catalysts in the body (derived from the Greek word “en” meaning inside and “zyme” meaning yeast).
• Enzyme Diversity: Each cell contains thousands of different enzymes, as almost every reaction requires a specific enzyme.

Structural Features of Enzymes

• Composition: Enzymes are mostly globular proteins, except ribozymes (RNA).
• Catalytic Power: Have high catalytic power, increasing reaction rates by a factor of 10^{20}.
• Hydration Example: Each molecule of an enzyme can hydrate 10^6 molecules of CO_2 per second.
• Specificity: Enzymes are highly specific in the reactions they catalyze and their choice of reactants.
• Cofactors: Many enzymes require a cofactor, which can be coenzymes or metal cofactors.

Cofactors

• Cofactors can be coenzymes or metal cofactors.

Nomenclature of Enzymes

• Naming Convention: Enzymes are commonly named based on the reaction they catalyze and/or the compound on which they act. For example, Lactate dehydrogenase catalyzes the removal of hydrogen from lactate.
• Exceptions: Some enzymes have older names (pepsin, trypsin, chymotrypsin) assigned before their actions were fully understood.

Six Major Classes of Enzymes

• Oxidoreductases: Catalyze oxidation and reduction reactions.
• Transferases: Catalyze the transfer of a group of atoms from one molecule to another.
• Hydrolases: Catalyze hydrolysis reactions.
• Lyases: Catalyze the addition of two groups to a double bond or the removal of two groups from adjacent atoms to create a double bond.
• Isomerases: Catalyze isomerization reactions.
• Ligases (Synthetases): Catalyze the joining of two molecules.

Enzymatic Activity

• Enzymes lower the activation energy of a reaction, making reactions faster.

Formation of the Enzyme-Substrate Complex

• ES Complex Formation: In an enzyme-catalyzed reaction, the enzyme (E) binds to the substrate (S) to form the ES complex.

Models of Binding the Substrate to Enzyme

• Lock-and-Key Model: The enzyme has a specific shape necessary to maintain the active site in the correct conformation for a particular reaction.
• Induced Fit Model: Substrate binding induces a conformational change in the enzyme, resulting in a complementary fit after the substrate is bound.

Nature of the Active Site

• Active Site Structure: The active site is a three-dimensional cleft or crevice formed by groups from different parts of the amino acid sequence.
• Common Amino Acids: The five most common amino acids in active sites (in order of dominance) are His > Cys > Asp > Arg > Glu. These are known as catalytic residues.

Factors Affecting Rate of Enzymatic Reaction

• Enzyme Concentration
• Temperature
• pH
• Enzyme Inhibition and Regulation

Enzyme Inhibition

• Enzyme Inhibitor: A substance that slows or stops the normal catalytic function of an enzyme by binding to it.

Enzyme Inhibition Types

• Irreversible Inhibitors: Inactivate enzymes by forming a strong covalent bond to an amino acid side-chain group at the enzyme’s active site.
• Competitive Inhibitors: Resemble an enzyme's substrate in shape and charge distribution, competing for occupancy of the enzyme’s active site.
• Non-competitive Inhibitors: Decrease enzymatic activity by binding to a site other than the active site, changing the enzyme's shape and affecting its active site.
• Uncompetitive Inhibitors: Decrease enzymatic activity by binding to the enzyme-substrate complex.

Regulatory Mechanism of Enzymes

• Regulation of enzyme activity within a cell is necessary because: (1) continually producing large amounts of enzymes for which substrate concentration is low wastes energy; and (2) a plentiful product is a waste of energy if the enzyme continues to catalyze its production.

Allosteric Enzymes

• Enzymes with quaternary structures containing two kinds of binding sites: one for the substrate and the other for the regulator (positive or negative).

Regulation of Enzymatic Activity

• Feedback Control: Activation or inhibition of the first reaction in a reaction sequence is controlled by a product of the reaction sequence (occurs for allosteric enzymes).
• Proteolytic Activation of Proenzymes: Proenzymes (zymogens) are inactive forms of enzymes that must be activated to perform catalytic functions. Pepsinogen, secreted by gastric chief cells, is converted by gastric acid in the gastric lumen to active pepsin.
• Covalent Modification: Enzyme activity is altered by covalently modifying the enzyme's structure through the attachment or removal of a chemical group to/from a particular amino acid within the enzyme’s structure.
• Isoenzymes: Enzymes that perform the same function but have different combinations of subunits and thus different quaternary structures.

Uses of Enzymes in Medicine

• Drugs that Inhibit Enzymatic Activity:
  • Angiotensin-Converting Enzyme (ACE) Inhibitors: ACE inhibitors inhibit the enzymes used to activate angiotensinogen to angiotensin, which increases blood pressure by narrowing blood vessels. The inhibition lowers blood pressure.
  • Sulfanilamide Antibiotics: Many bacteria need PABA to produce folic acid, an important coenzyme. Sulfanilamide acts as a competitive inhibitor to enzymes in the biosynthetic pathways for converting PABA into folic acid in these bacteria.
  • Penicillin: Penicillin inhibits bacterial transpeptidase, an enzyme that catalyzes the formation of peptide cross-links between polysaccharide strands in bacterial cell walls. Penicillin acts as a competitive and irreversible inhibitor for transpeptidase, weakening the bacterial cell wall.

Enzymes in Clinical Diagnosis

• Increased plasma levels of enzymes may indicate tissue damage, as a large number of enzymes are released from cells during normal cell turnover. The levels are normally fairly constant.
• For example, a certain isoenzyme for creatine kinase only occurs in the heart. Appearance of this isoenzyme in plasma is virtually specific for myocardial infraction (heart attack).