Chapter 12: Enzyme Kinetics, Inhibition, and Control Flashcards
Indicates the Progress of a Reaction as a Function of Time
A Rate Equation
occurs at high substrate concentrations when the enzyme is saturated
maximal velocity of a reaction, Vmax
is a measure of the affinity of the enzyme for its substrate
Km
another name for catalytic constant (kcat)
turnover number
the maximal number of molecules of substrate converted to product per active site per unit time of several different substrates to different products
catalytic constant (kcat)
a measure of an enzyme’s catalytic efficiency
kcat/Km
A better method for determining the values of Vmax and KM is
is Lineweaver–Burk or
double-reciprocal plot.
Most enzymatic reactions requiring multiple substrates and yielding multiple products
bisubstrate reactions
Reactions in which all substrates must combine with the enzyme before a reaction can occur and products be released are known as
sequential reactions.
Many NAD+ and NADP+ requiring dehydrogenases follow an what?
Ordered bisubstrate reaction
Some dehydrogenases and kinases operate through
random bisubstrate reaction
Group-transfer reactions in which one or more products are released before all substrates have been added are known as
Ping Pong reactions
In Ping Pong reactions, the substrates A and B do not what
encounter one another on the surface of the enzyme.
what enzymes react with Ping Pong
mechanisms
trypsin, transaminases, and some flavoenzymes
Substances that reduce an
enzyme’s activity in this way are known as
inhibitors
A substance that competes directly with a normal substrate for an enzyme’s substrate-binding site is known as a
competitive inhibitor.
are particularly effective inhibitors.
Transition state analogs
a citric acid cycle enzyme that converts succinate to fumarate,
succinate dehydrogenase
what inhibits succinate dehydrogenase
malonate
reduces the conc of free enzyme available for substrate binding.
A competitive inhibitor
what can overwhelm a competitive inhibitor.
concentration of substrate
significantly limits the production of the flu virus as a competitive inhibitor of influenza neuraminidase when is hydrolyzed to oseltamivir carboxylate in the liver
Tamiflu
hydrolyzes sialic acids of membrane
glycoproteins to help the viral particles escape from the host cell surface.
Neuraminidase
Comparing the KI values of competitive inhibitors with different structures can provide information
about what
the binding properties of an enzyme’s active site and hence its catalytic mechanism.
is the principle behind the use of ethanol to treat methanol poisoning
Competitive inhibition
are competitive inhibitors of dihydrofolate reductase.
Methotrexate and Trimethoprim
is used for cancer
chemotherapy
Methotrexate
is an effective antibiotic because it binds to bacterial dihydrofolate reductase nearly 100,000 times better than to the mammalian enzyme. It is used to treat certain urinary and middle ear bacterial infections
Trimethoprim
which need not resemble substrate, presumably distorts the active site, thereby rendering the enzyme catalytically inactive.
The binding of uncompetitive inhibitor
binds to enzyme sites that participate in both substrate binding and catalysis.
a mixed inhibitor
If the enzyme and enzyme–substrate complex bind I with equal affinity, then only Vmax is affected, a phenomenon that is named
pure noncompetitive inhibition.
does substrate binding reverse the effects of mixed inhibition
no
are non-competitive inhibitors of reverse transcriptase so they have been used to control HIV levels in AIDS.
Nevirapine or Delavirdine
is an uncompetitive and specific inhibitor of Type II 5-reductase, an enzyme that converts testosterone into dihydrotestosterone.
Finasteride
is believed to bind to the NADH cofactor of the enzyme.
Finasteride
how to control Enzyme availability
rates of synthesis and its rate of degradation controlled by the cell and is subject to dramatic changes over time spans
The amount of a given enzyme in a cell depends
rate of synthesis and its rate of degradation
can be directly controlled
through structural alterations that influence the enzyme’s substrate-binding affinity or turnover number
An enzyme’s catalytic activity
can cause large changes in enzymatic activity.
Allosteric mechanisms
ATCase is allosterically inhibited by
cytidine triphosphate (CTP)
it inhibits an earlier step in its own biosynthesis.
feedback inhibitor
allosterically reduce the activity of the catalytic subunits in the intact enzyme
The regulatory subunits
The most common covalent modification
reversible phosphorylation and dephosphorylation (the
attachment and removal of a phosphoryl group) of the hydroxyl group of a Ser, Thr, or T yr residue.
an important supplier of fuel for metabolic activities
glycogen breakdown
This is the rate-controlling step in the
metabolic pathway of glycogen breakdown
lycogen phosphorylase catalyzes the
phosphorolysis of glycogen to yield glucose-1-phosphate (G1P).
catalytically and structurally similar but genetically distinct enzymes from
the same organism;
isozymes also called isoforms
is regulated both by
allosteric interactions and by
phosphorylation/dephosphorylation.
Muscle glycogen phosphorylase
the phosphorylated
form of the enzyme
phosphorylase alpha
The dephospho form is called
phosphorylase beta
is inactive because it has a malformed active site and a surface loop that blocks substrate access to its binding site.
T -state enzyme
is allosterically controlled by the effectors AMP,A TP , and G6P and is mostly in the T state under
physiological conditions.
phosphorylase beta
is unresponsive to these
effectors and is mostly in the
phosphorylase alpha
A drug candidate that exhibits a desired effect is called a
lead compound
what makes a good lead compound
binds to its target protein with a dissociation constant (for an enzyme, an inhibition constant) of less than 1 μM. Such a high affinity is necessary to minimize a drug’s less specific binding to other macromolecules in the body and to ensure that only low doses of the drug need be taken
Even minor modifications to a drug candidate can result in what?
major changes in its pharmacological properties
uses the structure of a receptor or enzyme in complex with a drug candidate to guide the development of more efficacious compounds
Structure-based drug design (also called rational drug design
is the discipline within clinical pharmacology that broadly describes the changes in the quantity of drug and/or drug metabolite in various body compartments over time
pharmacokinetics
The most effective drugs are usually a compromise meaning
they are neither too
lipophilic nor too hydrophilic
