Enzyme Regulation and Blood Clotting Quiz

Enzyme Regulation and the Blood Clotting Cascade

• Enzyme activity can be regulated by controlling enzyme quantity or enzyme activity.
• Enzyme quantity can be regulated by controlling gene expression through transcription, translation, or enzyme turnover.
• Enzyme activity can be regulated through substrate and product concentration, changes in enzyme conformation through allosteric regulation, covalent modification, association-disassociation, or proteolytic cleavage of proenzyme.
• Allosteric enzymes are multi-subunit enzymes with more than one active site for the substrate, and their V vs [S] plots yield sigmoidal rate curves due to positive cooperativity.
• Allosteric control occurs through allosteric modifiers that can be stimulatory or inhibitory, shifting the curve left or right.
• Phosphofructokinase (PFK) is an allosteric enzyme that catalyzes the first committed step in glycolysis and is inhibited by phosphoenolpyruvate and activated by ADP.
• Covalent modification, particularly phosphorylation, can significantly affect enzyme conformation or substrate binding and is reversible through the action of kinase and phosphatase.
• Proteolytic activation occurs through zymogens, inactive protein precursors that are activated by the removal of part of the polypeptide chain, such as blood clotting factors.
• Enzyme synthesis can be regulated by controlling the rate of transcription of mRNA, while regulated protein degradation can control the amount of an enzyme.
• Metabolic pathways can be regulated through feedback inhibition, feedforward activation, or counter regulation of pathways.
• The blood clotting cascade is a tightly regulated process that involves the activation of zymogens, amplification of an initial signal, feedback activation by thrombin, and termination of clotting by multiple processes.
• Mechanisms involved in the regulation of the blood clotting cascade include the presence of inactive zymogens at low concentrations, amplification of an initial signal, feedback activation by thrombin, and termination of clotting by the removal of activated proteins, proteolytic digestion, and the binding of inhibitor molecules.

Enzyme Regulation and the Blood Clotting Cascade

• Enzyme activity can be regulated by controlling enzyme quantity or enzyme activity.
• Enzyme quantity can be regulated by controlling gene expression through transcription, translation, or enzyme turnover.
• Enzyme activity can be regulated through substrate and product concentration, changes in enzyme conformation through allosteric regulation, covalent modification, association-disassociation, or proteolytic cleavage of proenzyme.
• Allosteric enzymes are multi-subunit enzymes with more than one active site for the substrate, and their V vs [S] plots yield sigmoidal rate curves due to positive cooperativity.
• Allosteric control occurs through allosteric modifiers that can be stimulatory or inhibitory, shifting the curve left or right.
• Phosphofructokinase (PFK) is an allosteric enzyme that catalyzes the first committed step in glycolysis and is inhibited by phosphoenolpyruvate and activated by ADP.
• Covalent modification, particularly phosphorylation, can significantly affect enzyme conformation or substrate binding and is reversible through the action of kinase and phosphatase.
• Proteolytic activation occurs through zymogens, inactive protein precursors that are activated by the removal of part of the polypeptide chain, such as blood clotting factors.
• Enzyme synthesis can be regulated by controlling the rate of transcription of mRNA, while regulated protein degradation can control the amount of an enzyme.
• Metabolic pathways can be regulated through feedback inhibition, feedforward activation, or counter regulation of pathways.
• The blood clotting cascade is a tightly regulated process that involves the activation of zymogens, amplification of an initial signal, feedback activation by thrombin, and termination of clotting by multiple processes.
• Mechanisms involved in the regulation of the blood clotting cascade include the presence of inactive zymogens at low concentrations, amplification of an initial signal, feedback activation by thrombin, and termination of clotting by the removal of activated proteins, proteolytic digestion, and the binding of inhibitor molecules.

Enzymes and Enzyme Regulation

• Enzyme regulation can occur through changes in enzyme quantity or enzyme activity.
• Allosteric enzymes are multi-subunit enzymes with more than one active site for the substrate, and their V vs [S] plots yield sigmoidal rate curves due to positive cooperativity.
• The allosteric site is where a small molecule, known as an allosteric modifier, can bind and alter the affinity of the catalytic site to the substrate, either stimulatory or inhibitory.
• Phosphofructokinase (PFK) is an important regulatory enzyme that catalyzes the first committed step in glycolysis and is allosterically inhibited by phosphoenolpyruvate and activated by ADP.
• Covalent modification, particularly phosphorylation, is a reversible process that can significantly affect enzyme conformation or substrate binding and is catalyzed by kinase.
• Proteolytic activation involves the activation of inactive protein precursors, known as zymogens, by the removal of part of the polypeptide chain, and many proteases are produced in this form.
• Enzyme synthesis is regulated by increasing or decreasing the rate of transcription of mRNA, while regulated protein degradation controls the amount of an enzyme.
• Feedback inhibition, feedforward activation, and counter-regulation of pathways are mechanisms that regulate metabolic pathways.
• The blood clotting cascade is an example of a tightly regulated process, with inactive zymogens present at low concentrations to prevent accidental clotting.
• Damage to blood vessels initiates a cascade of activation resulting in the formation of an insoluble fibrin clot, which is terminated by removal of activated proteins, proteolytic digestion, and the binding of inhibitor molecules.
• Learning outcomes from this lecture include being able to list major regulatory mechanisms that control enzyme activity, discuss the allosteric properties of key regulatory enzymes, define the term zymogen and give examples of enzymes that are derived from zymogens, and explain how activation of the clotting cascade leads to the formation of a fibrin clot.
• References for this lecture include Marks' Basic Medical Biochemistry, Medical Biochemistry, and Lippincott’s Illustrated Reviews: Biochemistry.

Enzyme Regulation and Cascade

• Enzymes can be regulated by changes in enzyme conformation, substrate and product concentration, and changes in the amount of enzyme.
• Allosteric regulation involves the binding of a small molecule, called an allosteric modifier, to the allosteric site to alter the affinity of the catalytic site to the substrate.
• Covalent modification involves the addition or removal of a chemical group to a protein, which can significantly affect enzyme conformation or substrate binding.
• Enzyme synthesis and degradation can also regulate enzyme activity.
• Allosteric enzymes are multi-subunit enzymes containing more than one active site for the substrate, which yield sigmoidal rate curves due to positive cooperativity.
• Some rate-limiting enzymes in fuel oxidation pathways are allosteric enzymes, and other molecules can also bind to sites distinct from the active site to increase or decrease enzyme activity.
• Zymogens are inactive precursors of proteolytic enzymes that are activated by the removal of part of the polypeptide chain, and many proteases are produced in this form.
• Feedback inhibition, feedforward activation, and counter-regulation of pathways are mechanisms that regulate metabolic pathways.
• Enzymatic cascades involve a sequence of successive activation reactions involving enzymes, characterized by a series of amplifications stemming from an initial stimulus.
• Protein kinases and phosphatases regulate enzyme activity by adding or removing phosphate groups from proteins.
• Phosphorylation can make certain enzymes more active and other enzymes less active, depending on the specific enzyme.
• The blood clotting cascade is regulated by inactive zymogens, amplification of an initial signal, feedback activation by thrombin, and termination of clotting by multiple processes.

Enzyme Regulation and Enzyme Cascades

• Enzymes can be regulated by changes in enzyme conformation through the binding of a small molecule called an allosteric modifier, which can either increase or decrease enzyme activity.
• Allosteric control is one form of enzyme regulation, as well as covalent modification and proteolytic activation.
• Allosteric enzymes are multi-subunit enzymes that contain more than one active site for the substrate, resulting in sigmoidal rate curves due to positive cooperativity.
• Phosphofructokinase-1 (PFK-1) is an example of an allosteric enzyme that is rate-limiting in glycolysis and is regulated by allosteric activators and inhibitors, such as ATP, AMP, fructose 2,6-bisphosphate, and citrate.
• Covalent modification, such as phosphorylation, can also regulate enzyme activity by introducing a bulky, charged group that affects enzyme conformation or substrate binding.
• Enzyme synthesis can be regulated by controlling the rate of transcription of mRNA, and alterations in enzyme levels resulting from protein synthesis are slower than allosterically or covalently regulated changes in enzyme activity.
• Enzyme degradation can be regulated by controlling the rate of degradation, and proteins can be tagged for destruction by the addition of ubiquitin.
• Zymogens are inactive precursors of proteolytic enzymes that are activated by the removal of part of the polypeptide chain, such as blood clotting factors.
• Feedback inhibition, feedforward activation, and counter-regulation of pathways are mechanisms that regulate metabolic pathways.
• Enzyme cascades involve a sequence of successive activation reactions involving enzymes, characterized by a series of amplifications stemming from an initial stimulus.
• Protein kinases and phosphatases can regulate enzyme activity by catalyzing the addition or removal of a phosphate group from Ser/Thr/Tyr residues in a protein.
• The blood clotting cascade is an example of an enzyme cascade that involves the activation of inactive zymogens at low concentrations, amplification of an initial signal, feedback activation, and termination of clotting by multiple processes.

Enzyme Regulation and Enzyme Cascades

• Enzymes can be regulated by changes in enzyme conformation through the binding of a small molecule called an allosteric modifier, which can either increase or decrease enzyme activity.
• Allosteric control is one form of enzyme regulation, as well as covalent modification and proteolytic activation.
• Allosteric enzymes are multi-subunit enzymes that contain more than one active site for the substrate, resulting in sigmoidal rate curves due to positive cooperativity.
• Phosphofructokinase-1 (PFK-1) is an example of an allosteric enzyme that is rate-limiting in glycolysis and is regulated by allosteric activators and inhibitors, such as ATP, AMP, fructose 2,6-bisphosphate, and citrate.
• Covalent modification, such as phosphorylation, can also regulate enzyme activity by introducing a bulky, charged group that affects enzyme conformation or substrate binding.
• Enzyme synthesis can be regulated by controlling the rate of transcription of mRNA, and alterations in enzyme levels resulting from protein synthesis are slower than allosterically or covalently regulated changes in enzyme activity.
• Enzyme degradation can be regulated by controlling the rate of degradation, and proteins can be tagged for destruction by the addition of ubiquitin.
• Zymogens are inactive precursors of proteolytic enzymes that are activated by the removal of part of the polypeptide chain, such as blood clotting factors.
• Feedback inhibition, feedforward activation, and counter-regulation of pathways are mechanisms that regulate metabolic pathways.
• Enzyme cascades involve a sequence of successive activation reactions involving enzymes, characterized by a series of amplifications stemming from an initial stimulus.
• Protein kinases and phosphatases can regulate enzyme activity by catalyzing the addition or removal of a phosphate group from Ser/Thr/Tyr residues in a protein.
• The blood clotting cascade is an example of an enzyme cascade that involves the activation of inactive zymogens at low concentrations, amplification of an initial signal, feedback activation, and termination of clotting by multiple processes.

Enzyme Regulation and Enzyme Cascades

• Enzymes can be regulated by changes in enzyme conformation through the binding of a small molecule called an allosteric modifier, which can either increase or decrease enzyme activity.
• Allosteric control is one form of enzyme regulation, as well as covalent modification and proteolytic activation.
• Allosteric enzymes are multi-subunit enzymes that contain more than one active site for the substrate, resulting in sigmoidal rate curves due to positive cooperativity.
• Phosphofructokinase-1 (PFK-1) is an example of an allosteric enzyme that is rate-limiting in glycolysis and is regulated by allosteric activators and inhibitors, such as ATP, AMP, fructose 2,6-bisphosphate, and citrate.
• Covalent modification, such as phosphorylation, can also regulate enzyme activity by introducing a bulky, charged group that affects enzyme conformation or substrate binding.
• Enzyme synthesis can be regulated by controlling the rate of transcription of mRNA, and alterations in enzyme levels resulting from protein synthesis are slower than allosterically or covalently regulated changes in enzyme activity.
• Enzyme degradation can be regulated by controlling the rate of degradation, and proteins can be tagged for destruction by the addition of ubiquitin.
• Zymogens are inactive precursors of proteolytic enzymes that are activated by the removal of part of the polypeptide chain, such as blood clotting factors.
• Feedback inhibition, feedforward activation, and counter-regulation of pathways are mechanisms that regulate metabolic pathways.
• Enzyme cascades involve a sequence of successive activation reactions involving enzymes, characterized by a series of amplifications stemming from an initial stimulus.
• Protein kinases and phosphatases can regulate enzyme activity by catalyzing the addition or removal of a phosphate group from Ser/Thr/Tyr residues in a protein.
• The blood clotting cascade is an example of an enzyme cascade that involves the activation of inactive zymogens at low concentrations, amplification of an initial signal, feedback activation, and termination of clotting by multiple processes.