Lecture 12 – Enzymes I

Lecture 12 – Enzymes I

• Date: March 4th, 2025

• Reading Material: Biochemistry: Concepts and Connections, Chapter 8, Pages 233-250

Lecture Overview

• Disease for Today: Coenzymes and Pellagra

• Focus Topics:

  • Chapter 8 – Enzymes

    • Categories of enzymes: six categorizations

    • The kinetics of enzyme reactions

    • 1st and 2nd order reactions

    • Mechanism of enzymes speeding reactions

    • Role of coenzymes / cofactors

Disease of the Day - Pellagra

• Vitamin Deficiencies Overview:

  • Previously discussed Vitamin C and its deficiency leading to scurvy due to collagen breakdown

  • Nutritional diseases like Pellagra are rare but still occur, particularly in disadvantaged populations

• Key Terms:

  • Coenzymes/Cofactors:

    • Compounds associated with enzymes at or near the active site, essential for metabolic processes

  • Vitamins:

    • Organic molecules needed in small amounts for health, often serve as cofactors

Pellagra - Mechanism

• Vitamin B3 (Niacin):

  • Functions by producing

    • NAD+ (Nicotinamide Adenine Dinucleotide)

    • NADP (Nicotinamide Adenine Dinucleotide Phosphate)

  • Both are significant cofactors in enzyme reactions

• Consequences of Niacin Deficiency:

  • Results in insufficient production of NAD+ and NADP+ for enzyme functions

Pellagra - Symptoms

• Classic Symptoms:

  • The three "Ds":

    • Diarrhea

    • Dermatitis

    • Dementia

  • Fourth "D": Death

• Reason for Symptoms:

  • Niacin is critical in:

    • High turnover cell areas (e.g., epithelial lining)

    • High energy demand cells (nervous system)

Pellagra – Historical Context

• Often tied to poor diets characterized by:

  • Low meat consumption

  • Corn-based diet without proper processing

  • Corn has lower tryptophan levels compared to wheat/rice

• Alcoholism Connection:

  • High alcohol consumption can lead to niacin deficiency via:

    • Poor dietary intake

    • Impaired niacin metabolism

Enzymes: The Basics

• Enzymes are biological catalysts; most are proteins

• Substrate and Product:

  • Substrate: act upon enzymes

  • Product: created by enzymes

• Catalyst Rules:

  1. Enzymes are not consumed in reactions

  2. Enzymes accelerate reactions

• Categories of Enzymes: Six main types

The Six Categories of Enzymes

1. Oxidoreductases

   • Catalyze oxidation/reduction reactions

   • Example: Alcohol dehydrogenase, binds NAD+

2. Transferases

   • Transfer functional groups

   • Example: Hexokinase (glycolysis)

3. Hydrolases

   • Cleave molecules using water

   • Example: Peptide bond cleavage

4. Lyases

   • Cleavage without water

   • Example: Pyruvate decarboxylase

5. Isomerases

   • Rearrangement of substrate structures

   • Example: Maleate isomerase

6. Ligases

   • Join two molecules

   • Example: Pyruvate carboxylase

Examples of Enzymes

• Amylase:

  • Classification: Hydrolase; breaks down starch using water

• Phosphoglucose Isomerase:

  • Converts G6P to F6P (no water used, rearrangement)

First Order Reactions - Basics

• Enzymes operate at specific rates: amount of product/substrate per unit time

• First Order Reaction:

  • One substrate becomes one product: A → B

• Rate measurement options:

  1. v = d[B]/dt

  2. v = -d[A]/dt

• Rate dependency:

  • Rate decreases over time as substrate concentration decreases

Second Order Reactions

• More complex reactions: A + B → C

• Rate equation: v = k1[A]m[B]n (m and n can equal 1)

• Rate-limiting step: the slowest substrate or enzyme in the reaction

Factors Affecting Reaction Rates

1. Order of reaction

2. Concentrations of reactants

3. Temperature

4. Rate constant (k)

• Enzymes facilitate transition from high free energy to lower free energy

Graphical Representation of Reaction Pathways

• Free Energy Diagram

  • Shows the transition state and activation energy

• Example of pyranose (glucose) conformation transitions presented

Rate Enhancement via Enzymes

• Enzymes can significantly increase reaction rates

• Uncatalyzed reactions can take years versus enzyme-catalyzed reactions which can occur in seconds

• Example: Hydrolysis of peptide bonds

  • Uncatalyzed: 1/2500 years

  • Catalyzed: 238 times/second

  • Enhancement: 1 x 10^13 times faster

Specific Examples of Enzyme Rates

• Arginine decarboxylase (ADC):

  • Uncatalyzed: ~1 billion years

  • Catalyzed: ~1000 times/second

Theory Behind Reaction Rates

• Active sites: Specific regions where substrates bind

• Enzyme Models:

  • Lock and Key: specificity based on shape complementarity

  • Induced Fit Hypothesis: Enzyme changes shape to stabilize transition state

Coenzymes and Vitamins

• Coenzymes: Bound ions or molecules aiding enzyme reactions

• Vitamins: Organic molecules required in small amounts for health

  • Often function as full or part of coenzymes

Important Coenzymes and Associated Vitamins

Metal Cofactors

• Essential trace elements for enzyme activity

• Facilitate crucial enzymatic reactions

  • E.g., Iron in redox reactions, Zinc in NAD+ binding

Metal Cofactors Table

Upcoming Class

• Continuing discussion of enzymes scheduled for Thursday

• Expect tests to be returned by then