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2 kinds of enzyme inhibition
competitive inhibitor and noncompetitive inhibitor
competitive inhibitor
directly competes with binding of substrate to active site
noncompetitive inhibitor
binds enzyme at site other than active site and changes enzymes shape so that it becomes less active
effectiveness of an inhibitor has to do with what?
the affinity of an enzyme with inhibitor
there can be instances where there's high affinity to inhibitor vs. substrate due to difference in?
bulkiness of structures
one way to overcome competitive inhibition is?
increase amount of natural substrate which increases the likelihood if enzyme coming into contact with natural substrate
sulfa drugs block pathway for?
folic acid synthesis
you want to target?
pathways that bacteria cells have and we don't
low km = ?
high affinity
does an enzyme change the amount of free energy?
no
does an enzyme convert a non-spontaneous rxn into a spontaneous one?
no
noncompetitive inhibition induces?
conformational change
example of a noncompetitive inhibitor
heavy metals
3 major mechanisms of metabolic regulation
metabolic channeling, regulation of the synthesis of a particular enzyme and direct stimulation or inhibition enzyme
metabolic channeling is used more heavily in?
eukaryotic cells
in metabolic channeling you can?
move things around and compartmentalized
metabolic channeling
differential localization of enzymes and metabolites
compartmentation
differential distribution of enzymes and metabolites among separate cell structures or organelles
we associate compartmentation more with?
eukaryotes because we have more places to move things around
compartmentation can generate marked variations in?
metabolite concentrations
metabolic channeling allows us to operate different pathways?
simultaneously
metabolic channeling allows us to regulate transport of products from?
one pathway to another
eukaryotic organism folic acid catabolism is in?
mitochondria
eukaryotic organism folic acid is synthesized in?
cytosol
post-translational regulation of enzyme activity - 2 important reversible control measures
allosteric regulation and covalent modification
majority of regulatory enzymes used what reversible control method?
allosteric regulation
non-competitive inhibitors are a type of?
allosteric regulation
allosteric regulation is actively altered by?
small molecule
allosteric effector
binds noncovalently at regulatory site
allosteric effector changes shape of?
enzyme and alters activity of catalytic site
a positive effector?
increases enzyme activity allowing natural substrate to bind
a negative effector?
inhibits the enzyme
if a natural substrate neets an allosteric effector to bind with enzyme will it work without it? (example of a positive effector)
no
covalent modification of enzymes acts as an?
on/off switch for enzyme
covalent modification adds or removes?
functional/chemical groups
by covalently modificating something it?
changes activity of enzymes itself
advantages of covalent modification
respond to more stimuli in varied and sophisticated ways and regulation of enzymes that catalyze covalent modification adds second level
covalent modification glutamine synthetase of E. coli - made up of?
12 different subunits
glutamine synthetase is fully functional without?
adenylyl groups
glutamine synthetase in off when?
all 12 adenylyl groups are on
feedback inhibition is also called?
end product inhibition
why is it called end product inhibition?
when cells don't used end product the pathway to make it will get inhibited
inhibition of one or more critical enzymes in a pathway regulates?
entire pathway
pathway always regulates?
pacemaker enzyme
pacemaker enzyme is usually the?
1st enzyme in pathway
pacemaker enzyme catalyzes?
the slowest or rate-limiting reaction in the pathway
when a pathway shuts down does it shut down forever?
no only until end product concentration dies down
each end product in feedback inhibition regulates?
its own pathway and the initial pacemaker enzyme
if you see a branch point what does it mean?
it is another site for shutting down pathway
what happens if you there is a buildup of end product P but not end product Q?
end product P can shut down its own pathway without shutting down end product Q's pathway