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Page 1: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes
Page 2: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Factors Affecting Enzymatic Activity Enzyme Inhibition Regulation of Enzyme Activity Clinical Applications of Enzymes

Enzymes

Page 3: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Factors Affecting Enzymatic Activity

Page 4: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Enzymes are most active at an optimum temperature (usually 37°C in humans).

Enzymes show little activity at low temperatures. Enzymes lose activity at high temperatures as

denaturation occurs.

Temperature and Enzyme Action

Page 5: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

pH and Enzyme Action

Each enzyme exhibits peak activity at narrow pH range (optimum pH).

Enzymes contain R groups of amino acids with proper charges at optimum pH.

Enzymes lose activity in low or high pH as tertiary structure is disrupted.

Page 6: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Optimum pH reflects

the pH of the body

fluid in which the

enzyme is found.

pH and Enzyme Action

Page 7: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Optimum pH Values

Most enzymes have an optimum pH of about 7.4 In certain organs, enzymes operate at different

pH values.

Page 8: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Enzyme Concentration The rate of reaction increases as enzyme

concentration increases (at constant substrate concentration).

At higher enzyme concentrations, more substrate binds with enzyme.

Page 9: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Substrate Concentration The rate of reaction increases as substrate

concentration increases (at constant enzyme concentration).

Maximum activity occurs when the enzyme is saturated.

Page 10: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Enzyme Inhibition

Page 11: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Inhibitors: Are molecules that cause a loss of catalytic

activity. Prevent substrates from fitting into the active

sites.

E + S ES E + P

E + I EI no P

Enzyme Inhibition

Page 12: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Reversible Competitive Inhibition

A competitive inhibitor: Has a structure like the

substrate. Competes with the

substrate for the active site.

Has its effect reversed by increasing substrate concentration.

Page 13: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

A noncompetitive inhibitor: Has a structure different than

the substrate. Distorts the shape of the

enzyme, which alters the shape of the active site.

Prevents the binding of the substrate.

Cannot have its effect reversed by adding more substrate.

Noncompetitive irreversible Inhibition

Page 14: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Malonate and Succinate Dehydrogenase

Malonate: Is a competitive inhibitor of succinate

dehydrogenase. Has a structure that is similar to succinate. Inhibition is reversed by adding succinate.

Page 15: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Loss of all enzymatic activity Toxic substance (irreversible inhibitor) forms a

covalent bond with an amino acid in the active center. Prevents the substrate from entering the active

site. Prevents the catalytic activity.

Examples: insecticides and nerve gases inhibit the enzyme acetylcholinesterase (needed for nerve conduction).

Page 16: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes
Page 17: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Irreversible Inhibition In irreversible inhibition, a substance destroys

enzyme activity by bonding with R groups at the active site.

Page 18: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Zymogens (proenzymes)

Are inactive forms of enzymes. Are activated when one or more peptides are

removed. Such as proinsulin is converted to insulin by

removing a small peptide chain.

Page 19: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Digestive Enzymes

Produced as zymogens in one organ and transported to another such as the pancreas when needed.

Activated by removing small peptide sections.

Page 20: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Allosteric Enzymes

An allosteric enzyme is an enzyme in a reaction sequence that binds a regulator substance.

A positive regulator enhances the binding of substrate and accelerates the rate of reaction.

A negative regulator prevents the binding of the substrate to the active site and slows down the rate of reaction.

Page 21: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Feedback Control

A product acts as a negative regulator. An end product binds with the first enzyme (E1) in a

sequence, when sufficient product is present.

Page 22: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Clinical Applications of Enzymes

Page 23: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Diagnostic Enzymes

The levels of diagnostic enzymes determine the amount of damage in tissues.

Serum Enzymes used in diagnosis of tissue damage

Page 24: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes
Page 25: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Hepatitis

A 36-year old man was admitted to a hospital following episodes of nausea, vomiting, and general malaise.

His urine was darker than usual. Upon examination it was discovered that his liver

was enlarged and tender to palpation.

Clinical examples and case studies.

Page 26: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Hepatitis Liver function tests were abnormal:

Plasma ALT (Alanine aminotransferase) was 1500 U/L (6.0 – 21 U/L).

Plasma AST (Aspartate aminotransferase) was 400 U/L (7.0 – 20 U/L).

During the next 24 hours the man developed jaundice, and his plasma total bilirubin was 9.0 mg/dL (0.2 – 1 mg/dL).

A diagnosis of hepatitis was made.

Clinical examples and case studies.

Page 27: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Hepatitis

Clinical examples and case studies.

What reactions are catalyzed by AST and ALT? What is the coenzyme?

Page 28: Factors Affecting Enzymatic Activity  Enzyme Inhibition  Regulation of Enzyme Activity  Clinical Applications of Enzymes Enzymes

Case discussion:Hepatitis is an inflammation of the liver

Transaminases (amino acids metabolism)– Catalyze the transfer of α-amino groups from

amino acid to a α-keto acid through the intermediary coenzyme pyridoxal phosphate (derived from the B6 vitamin, pyridoxine)

– Amino acids enter into the Krebs cycle for oxidation to CO2 and H2O

– Amino acid X + keto acid Y ↔ amino acid Y + keto acid X

– ALT and AST


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