PPT Enzyme: Regulation Of Activity - Dr. Bonleon Flashcards
Cannot respond to an increase in substrate concentration
Maximal rate
Average intracellular concentration of their substrates tends to be close to the __________.
Km value
Changes in substrate concentration generate corresponding changes in ___________.
Metabolic flux
Coordinating metabolite flow and maintaining homeostasis in quiescent cells
Passive
Limited scope for responding to changes in environmental variables
Passive
Responses to changes
Passive
Mean concentrations of metabolic intermediates remain relatively constant over time
Dynamic steady state
With overall change in free energy that favors UNIDRECTIONAL metabolite flow
Coupled metabolic reactions
Pathway with a large overall negative charge in free energy
Unidirectional flow
Bends or kink (enzyme cat steps)
Unidirectional flow
Ability to maintain a constant intracellular environment despite changes in the external environment
Homeostasis
*Organisms respond to changes (external and internal)
Balanced, coordinated changes in the rates of specific metabolic reactions
Homeostasis
Ensures metabolic efficiency
Compartmentation
Simplifies regulation
Compartmentation
Anabolic and catabolic pathways that interconvert common products may take place in specific subcellular compartments
Compartmentation
Segregation of metabolic pathways
Compartmentation
One or more unique intermediates can permit opposing pathways to coexist even in the absence of physical barrier
Physical compartmentation
Enzymes discriminate between the structurally similar conezymes
Compartmentation
Quantity or catalytic efficiency dictates that the reaction or catalysis is slow relative to all others in the pathway
Ideal enzyme
Reduces metabolite flux through the entire pathway
Rate-limiting reaction
Increase in either its quantity of catalytic efficiency enhances flux through the pathway as a whole
Ideal enzyme
Catalyze the rate-limiting steps
Ideal enzyme
Constitute efficient targets for regulatory intervention
Ideal enzyme
Product of the concentration of enzyme molecules and their intrinsic catalytic efficiency.
Catalytic capacity of the rate-limiting reaction in a metabolic pathway
Influenced by both changing the quantity of enzyme present and by altering its intrinsic catalytic efficiency
Catalytic capacity
Enzymes whose concentrations remain constant over time.
Constitutive enzymes
Substrates or structurally related compounds that initiate their syntheis and depended on by other enzymes
Inducers
Way by which an excess of a metabolite may curtail synthesis of its cognate enzyme
Repression
Absolute quantity of an enzyme reflects the net balance between enzyme synthesis and enzyme degradation
Enzyme degradation
Net result of enzyme synthesis and degradation
Protein turnover
Body is in a state of ______________
Dynamic equilibrium
__________ and ___________ is a continuous process.
Synthesis and degradation
Enzyme levels respond to:
- Physiologic
- Hormonal
- Dietary
Proteolytic degradation influenced by presence of ___________, substrates, coenzymes or metal ions that alter protein conformation.
Ligands
Changes in ______ can alter ionization state of the substrate or the enzyme-binding site for substrate.
pH
Changes in _______ can alter ionization state at the catalytic site on the enzyme
pH
Changes in pH can alter _________ so that their conformation and catalytic activity change
Protein molecules
Rate of an enzyme-catalyzed reaction __________ in temperature up to an optimum point then it _______ because enzymes are THERMOLABILE.
Increase
Decrease
If the product accumulates, it can inhibit some enzymes.
Product inhibition
Limits the rate of formation of the product when the product is underused.
Product inhibition
Inhibition of an enzyme in a biosynthetic pathway by end products of that pathway not by “backing-up” of intermediates but from the ability of the end product to bind to and inhibit the enzyme.
Feedback inhibition
Intrinsic catalytic efficiency effected by binding of dissociable ligands.
Allosteric regulation
Serve long-term adaptive requirements
Changes in protein level
For rapid and transient alterations in metabolite flux
Changes in catalytic efficiency
Key regulatory enzymes (committed steps) subjected
Allosteric regulation
Activity modulated by binding of allosteric effectors to a site on the enzyme distinct from the active site
Allosteric regulation
Negative modulation of the committed step of a metabolic pathway by its end product.
Feedback inhibition
Prevents unnecessary production of an excess of end product by shutting down the pathway until more is needed
Feedback inhibition
End product binds at an ___________.
Allosteric site
*Distinct from the catalytic site of the target enzyme
If they enhance the rate of a reaction
Positive
Activators
Positive
If they decrease the rate of reaction
Negative
Inhibitors
Negative
Bear little or no structural similarity to the substrates of the enzymes they inhibit
Allosteric effectors
End product may acts as “______________”
Negative allosteric effector
Small molecule building blocks of macromolecules
Allosteric effectors
Typically inhibit the 1st committed step in a biosynthetic sequence
Allosteric effectors
End product typically only partially inhibits catalytic activity
Cooperative feedback inhibition
Effect of an excess of 2 or more end products may be strictly additive or greater than their individual effect
Cooperative feedback mechanism
Effectors are not isosteric with a substrate
Allosteric regulation
Lack of structural similarity between a feedback inhibitor and the substrate for the enzyme whose activity it regulates.
Allosteric regulation
Occupy another space
Allosteric
Physically distinct from the catalytic site
Allosteric regulation
Those whose activity at the active site may be modulated by the presence of effectors an allosteric site
Allosteric enzymes
Substrate saturation kinetics are competitive
K-series
The Km is raised without an effect in Vmax
K-series
Conformational change may weaken the bonds between substrate and substrate-binding residues
K-series
Allosteric inhibitor lowers Vmax without affecting the Km
V-series
Alterations in Km and Vmax result from conformational changes at the catalytic site induced by binding of the allosteric effector at the allosteric site
V-series
Primary effect may be to alter the orientation or charge of catalytic residues, lowering vmax
V-series
The addition of a phosphate group to a specific amino acid residue (Ser, Tyr, Thr) by specific protein kinases dramatically enhance or depress activity
Phosphorylation
May be dephosphorylated by specific phosphatases and reversible
Phosphorylation
Activities of some enzymes are regulated by the reversible addition of a nucleotide to a specific amino acid.
Nucleotidylation
An adenylated enzyme may be deadenylated by a specific enzyme and reversible.
Nucleotidylation
Some enzymes are synthesized as proenzymes or zymogens (inactive forms)
Proteolytic cleavage
Activated by being cleaved at a specific site in their polypeptide chain by specific proteases
Proteolytic cleavage
Digestive enzymes that hydrolyze proteins
Proteolytic cleavage
Blood clotting mediated by proteolytic zymogen activities of several serum enzymes
Proteolytic cleavage
Devoid of mechanistic implications
Feedback regulations
Mechanism for regulation of enzyme activity
Feedback inhibition
Virtually all reactions in the body are mediated by____________.
enzymes
____________ are protein catalysts that increase the rate of reactions without being changed in the overall process.
Enzymes
Enzymes selectively channel reactants (__________) into useful pathways.
substrates
Enzymes are ___________ increase the velocity of a chemical reaction.
catalysts
_____________ isolate the reaction substrate or product from other competing reactions m provide purposeful pathways.
Compartmentalization
