ENZYMESCourse Title: Basic PharmaceuticalsCourse Code: ACCE 262Applied Chemistry & Chemical Engineering

SHAIKH ASHRAFUL ALAM

ENZYMESA substance produced by a living organism

which acts as a catalyst to bring about a specific biochemical

reaction.

Classification of Enzymes

OxidoreductasesTransferases HydrolasesLyasesIsomerasesLigases

Enzyme structure Enzymes are

proteins They have a

globular shape A complex 3-D

structure

Part of Enzyme

Enzyme

Pyruvate Dehydrogenase(active form) Inactive form(apo enzyme)

Prosthetic group

Cofactor(Inorganic or Metal ion)

Co-enzyme(Organic ion)

Properties of Enzymes

Most enzymes are proteinsThey are all biological catalystA small amount of enzyme can effect the change of a large amount of

chemical.Enzymes work is affected by temperature, pH and pressure.They can be destroyed by excessive heat.The reaction are reversible.

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Enzymes

FreeEnergy

Progress of the reaction

Reactants

Products

Free energy of activation

Without EnzymeWith Enzyme

Factors Affecting Enzymes

Substrate concentrationpHTemperatureInhibitors

Mechanism of enzyme action

Lock and key theoryInduced fit mechanism

LOCK AND KEY MODELThe lock and key model of enzyme action, proposed earlier this century, proposed that the substrate was simply drawn into a closely matching cleft on the enzyme molecule.

Substrate

Enzyme

Products

Symbolic representation of the lock and key model of enzyme action.1. A substrate is drawn into the active sites of the enzyme.

2. The substrate shape must be compatible with the enzymes active site in order to fit and be reacted upon.

3. The enzyme modifies the substrate. In this instance the substrate is broken down, releasing two products.

INDUCED FIT MODELMore recent studies have revealed that the process is much more likely to involve an induced fit.

The enzyme or the reactants (substrate) change their shape slightly.

The reactants become bound to enzymes by weak chemical bonds.

This binding can weaken bonds within the reactants themselves, allowing the reaction to proceed more readily.

The enzyme changes shape, forcing the substrate molecules to combine.

Two substrate molecules are drawn into the cleft of the enzyme.

The resulting end product is released by the enzyme which returns to its normal shape, ready to undergo more reactions.

Induced Fit• A change in the shape of an enzyme’s active site

• Induced by the substrate

Induced Fit• A change in the configuration of

an enzyme’s active site (H+ and ionic bonds are involved).

• Induced by the substrate.

Enzyme

Active Sitesubstrate

induced fit

Inhibitors

Inhibitors are chemicals that reduce the rate of enzymic reactions.

The are usually specific and they work at low concentrations.

They block the enzyme but they do not usually destroy it.

Many drugs and poisons are inhibitors of enzymes in the nervous system.

Two examples of Enzyme Inhibitors

a. Competitive inhibitors: are chemicals that resemble an enzyme’s normal substrate and compete with it for the active site.

EnzymeCompetitive inhibitor

Substrate

Inhibitorsb. Noncompetitive inhibitors:

Inhibitors that do not enter the active site, but bind to another part of the enzyme causing the enzyme to change its shape, which in turn alters the active site.

Enzymeactive site altered

NoncompetitiveInhibitorSubstrate

Use of Enzyme activators

Enzyme activators are molecules that bind to enzymes and increase their activity.

They are the opposite of enzyme inhibitors.

These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism.

Specificity of Enzyme

• Stereospecificity CH2COOH H-C-COOH

CH2COOH HOOC-C-H

Succinic acid Fumaric acid

Specificity of Enzyme (reaction specificity)

COOH COOH CH

CH2 CH CO

C.OH.COOH CO2 COOH

CH2 COOH

COOH

(+ CH3COOH) Decarboxylation

Citric acid

Pyruvic acid

Specificity of Enzyme (reaction specificity) Oxaloacetic acid

COOH COOH

CH2 CH2

CHOH CHNH2

COOH COOHMalic acid Aspartic acid

Enzymatic reactions of oxaloacetic acid

Specificity of Enzyme (substrate specificity)

NH2CONH2 2NH3 + CO2

H2O

Urease

Summary: Enzymes

• Enzymes work very rapidly and help to speed up biological reactions.

• Enzymes can be used multiple times (however they do degrade eventually).

• Enzymes can work in both directions of a chemical reaction.

• Enzymes have optimal temperatures and pH that they will operate. Beyond these optimum ranges they will either not work or become denatured (unfolded/breakdown).

• Enzymes are usually specific to one particular substrate.