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Factors Affecting Enzymatic ActivityEnzyme InhibitionRegulation of Enzyme ActivityClinical Applications of EnzymesEnzymesFactors Affecting Enzymatic ActivityEnzymes are most active at an optimum temperature (usually 37C 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 Action6Optimum pH ValuesMost enzymes have an optimum pH of about 7.4In certain organs, enzymes operate at different pH values.

Enzyme ConcentrationThe rate of reaction increases as enzyme concentration increases (at constant substrate concentration). At higher enzyme concentrations, more substrate binds with enzyme. Substrate ConcentrationThe rate of reaction increases as substrate concentration increases (at constant enzyme concentration).Maximum activity occurs when the enzyme is saturated.

Enzyme InhibitionInhibitors: Are molecules that cause a loss of catalytic activity.Prevent substrates from fitting into the active sites.

E + SESE + P

E + I EIno P

Enzyme InhibitionReversible Competitive InhibitionA 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 InhibitionMalonate and Succinate DehydrogenaseMalonate: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 activityToxic 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 InhibitionIn 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 EnzymesProduced as zymogens in one organ and transported to another such as the pancreas when needed. Activated by removing small peptide sections.

Allosteric EnzymesAn 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 ControlA 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 EnzymesDiagnostic Enzymes The levels of diagnostic enzymes determine the amount of damage in tissues.

Serum Enzymes used in diagnosis of tissue damage

HepatitisA 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.HepatitisLiver 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.HepatitisClinical examples and case studies.What reactions are catalyzed by AST and ALT? What is the coenzyme?Case discussion:Hepatitis is an inflammation of the liverTransaminases (amino acids metabolism)Catalyze the transfer of -amino groups from amino acid to a -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 H2OAmino acid X + keto acid Y amino acid Y + keto acid XALT and AST

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