BIOC3021 #9 - Enzyme Regulation

Enzyme Specificity

The ability of an enzyme to catalyze only one particular reaction

Enzyme Specificity Hypotheses

1. Lock & Key Hypothesis: considers the enzyme to resemble the “lock” and the substrate the “key”

2. Induced Fit Hypothesis: considers the modification of an enzyme’s active site upon binding

Mechanisms of Enzyme Regulation

1. Reverse Reaction: conversion of product to substrate

2. Availability: substrates and cofactors

3. Genetic Controls: gene induction/repression

4. Covalent Modification: reversible attachment of chemical groups

5. Specialized Controls: zymogens, isozymes, and modulator proteins

6. Allosteric Regulation: an activator/inhibitor binds to the enzyme at a site different than the active site

Regulation of Enzyme Activity by Reversible Covalent Attachment of Phosphate Groups ➡ What allows phosphate group bonding?

Hydroxyl (-OH) on the R-side-chain allows phosphate group(s) to attach to the amino acid

Regulation of Enzyme Activity by Specialized Controls of Zymogens

Zymogens: inactive precursors of enzymes that acquire full activity by specific cleavage of one or more peptide bonds of protein

Examples of Zymogens

1. Insulin

2. Proteolytic Enzymes

3. Blood Clotting Factors

Insulin

Regulates glucose ➡ Generated by excision of a specific peptide from proinsulin

Insulin is split across the polypeptide chains…

A-Chain (21 amino acids) and B-Chain (30 amino acids) that are connected through 3 disulfide bonds

Proteolytic Enzymes

Break down dietary proteins ➡ Synthesized as zymogens in the pancreas and stomach

Ex. Activation of Chymotrypsinogen by Proteolytic Enzymes Process

• Chymotrypsinogen ➡ π Chymotrypsinogen

• π Chymotrypsinogen ➡ σ Chymotrypsinogen

• σ Chymotrypsinogen ➡ α Chymotrypsinogen

• α Chymotrypsinogen: fully active in breaking down dietary proteins

Blood Clotting Factors

Form blood clots ➡ Produced by activation of zymogens of clotting factors

Blood Clotting Factors have both the…

Extrinsic pathway (tissue factor) and Intrinsic pathway (contact activation pathway) converging at Factor X

Regulation of Enzyme Activity by Specialized Controls of Isozymes

Isozyme: Form of an enzyme that differs in its quaternary structure, with different numbers of distinct polypeptide subunits

Examples of Isozymes

• Lactase Dehydrogenase (LDH): exists as five different enzymes, which vary in their enzymatic properties

Types of Lactase Dehydrogenase

• Skeletal Muscle LDH: Mainly A4 isozyme, which produced lactice acid in anaerobic conditions

• Heart Muscle LDH: Mainly B4 isozyme, which uses lactic acid in aerobic conditions

Regulation of Enzyme Activity by Specialized Controls of Modulator Proteins

Modulator Proteins: Proteins that bind to enzymes, thereby influencing their activity

Examples of Modulator Proteins

• cAMP-Dependent Protein Kinase: Consists of catalytic (C) subunits that are enzymatically active AND regulatory (R) subunits that are modulator proteins that bind to the (C) subunits, inhibiting activity