Chapter 8 ENZYMES: KINETICS Flashcards
the quantitative measurement of the rates of enzyme-catalyzed reactions and the systematic study of factors that affect these rates, constitutes a central tool for the analysis, diagnosis, and treatment of the enzymic imbalances that underlie numerous human diseases
Enzyme kinetics
In the blood, the appearance or a surge in the levels of particular enzymes serve as
clinical indicators for pathologies such as myocardial infarctions, prostate cancer, and damage to the liver
lists the initial chemical species (substrates) present and the new chemical species (products) formed for a particular chemical reaction, all in their respective proportions or stoichiometry
balanced chemical equation
The term often used to designate the reactants whose formation is thermodynamically favored
“products”
used to describe reactions in living cells where the products of reaction (2) are immediately consumed by a subsequent enzyme-catalyzed reaction or rapidly escape the cell, for example, CO2
Unidirectional arrows
describes in quantitative form both the direction in which a chemical reaction will tend to proceed and the concentrations of reactants and products that will be present at equilibrium
Gibbs free energy (change ΔG)
True or False
The sign and the magnitude of the free energy change
determine how far the reaction will proceed.
True
True or False
If ΔG^0 is a negative number, Keq will be greater than unity, and the concentration of products at equilibrium will exceed that of the substrates.
True
True or False
If ΔG^0 is positive, Keq will be less than unity, and the formation of substrates will be favored.
True
is independent of the mechanism of the reaction, and provides no information concerning rates of reactions
ΔG^0
The concept of the ____ is fundamental to understanding the chemical and thermodynamic basis of catalysis.
Transition state
also called the collision theory—of chemical kinetics states that for two molecules to react they
(1) must approach within bond-forming distance of one another, or “collide,” and
(2) must possess sufficient kinetic energy to overcome the energy barrier for reaching the transition state.
kinetic theory
The sum of the molar ratios of the reactants defines the ______ of the reaction.
kinetic order
is the factor by which the rate of a biologic process increases for a 10 degree celsius increase in temperature
Temperature coefficient
referred to as the variable reactant or substrate, can be determined by maintaining the concentration of the other reactants in large excess over the variable reactant
Kinetic Order
True or False
All enzymes accelerate reaction rates by lowering ΔGf for
the formation of transition states.
True
Catalysis by enzymes that proceeds via a unique reaction
mechanism typically occurs when the transition state intermediate forms a covalent bond with the enzyme
Covalent Catalysis
The rate of almost all enzyme-catalyzed reactions exhibits a
significant dependence on ______.
hydrogen ion concentration
Most intracellular enzymes exhibit optimal activity at pH values
between 5 and 9
Most measurements of the rates of enzyme-catalyzed reactions employ relatively short time periods, conditions that are considered to approximate ______
initial rate conditions
illustrates in mathematical terms the relationship between initial reaction velocity vi and substrate concentration [S]
Michaelis-Menten equation
used to determine the kinetic mechanism of an enzyme inhibitor
Lineweaver-Burk plot
The activity of impure enzyme preparations typically is
expressed as a
specific activity
is an exclusive property of multimeric enzymes that bind substrate at multiple sites
Cooperative Behavior
For enzymes that display positive cooperativity in binding
the substrate, the shape of the curve that relates changes in vi to changes in [S] is
Sigmoidal
originally derived to describe the cooperative binding of O2 by hemoglobin
Hill equation
In Hill equation, If n is greater than 1, the enzyme is said to exhibit
positive cooperativity
Compounds that mimic the transition state of an enzyme catalyzed reaction
transition state analogs
Compounds that take advantage of the catalytic machinery of an enzyme
mechanism-based inhibitors
the inhibitor (I) binds to the substrate-binding portion of the active site thereby blocking access by the substrate.
competitive inhibition
The structures of most classic competitive inhibitors therefore tend to resemble the structure of a substrate, and thus are termed ____
substrate analogs
____ acts by decreasing the number of free enzyme molecules available to bind substrate, that is, to form ES, and thus eventually to form product
competitive inhibitor
True or False
a competitive inhibitor has no effect on Vmax but raises
K′m, the apparent Km for the substrate.
True
is sometimes employed as an alternative to the
Lineweaver-Burk plot for determining inhibition constants.
Dixon plot
are substrate analogs that bind to the active site, preventing enzyme-substrate complex formation
Competitive inhibitors
substrate analogs transformed by the catalytic machinery of the enzyme into a product that blocks the function of the same catalytic subunit.
Suicide or mechanism based inhibitors
bind to the free enzyme and enzyme-substrate complex at the allosteric site and lower the catalytic efficiency of the enzyme.
Simple noncompetitive inhibitors
used both to distinguish between competitive and noncompetitive inhibitors and to simplify evaluation of inhibition constants.
Double-reciprocal plots
applies to mechanisms in which one or more products are released from the enzyme before all the substrates have been added
Ping-pong
involve covalent catalysis and a transient, modified form of the enzyme
Ping-pong reactions
Ping-pong Bi-Bi reactions are often referred to as
double displacement reactions
are used to complement kinetic analyses and to distinguish between ordered and random Bi-Bi reactions
Product inhibition studies
a drug needs to be resistant to degradation by enzymes present in the patient or pathogen
drug metabolism
Inhibitor looks like substraye and competes for same active site; Km is increased and Vmax has not changed
Competitive inhibitors
Inhibitor binds to another site different from active site; Km not changed; Vmax lowered
Noncompetitive inhibitors
Vmax/protein
- to compare impure preparations of same enzyme
Specific Activity
Vmax/mol of enzyme; to compare across homogenous enzymes
Turnover Number
Vmax/Number of active sites
Catalytic Constant
Type of Inhibitoon on HGM-CoA reductase; Dihhdrofolate reductase; Angiotensin converting enzyme
Competitive
Type of inhibition in Thymidilate synthase; cyclooxugenase; bacterial transpeptidase and monoamine oxidase
Suicide
