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Factors Affecting Enzymatic Activity Enzyme Inhibition Regulation of Enzyme Activity Clinical Applications of Enzymes
Enzymes
Factors Affecting Enzymatic Activity
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
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.
Optimum pH reflects
the pH of the body
fluid in which the
enzyme is found.
pH and Enzyme Action
Optimum pH Values
Most enzymes have an optimum pH of about 7.4 In certain organs, enzymes operate at different
pH values.
Enzyme Concentration The rate of reaction increases as enzyme
concentration increases (at constant substrate concentration).
At higher enzyme concentrations, more substrate binds with enzyme.
Substrate Concentration The rate of reaction increases as substrate
concentration increases (at constant enzyme concentration).
Maximum activity occurs when the enzyme is saturated.
Enzyme Inhibition
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
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.
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
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.
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).
Irreversible Inhibition In irreversible inhibition, a substance destroys
enzyme activity by bonding with R groups at the active site.
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.
Digestive Enzymes
Produced as zymogens in one organ and transported to another such as the pancreas when needed.
Activated by removing small peptide sections.
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.
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.
Clinical Applications of Enzymes
Diagnostic Enzymes
The levels of diagnostic enzymes determine the amount of damage in tissues.
Serum Enzymes used in diagnosis of tissue damage
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.
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.
Hepatitis
Clinical examples and case studies.
What reactions are catalyzed by AST and ALT? What is the coenzyme?
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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