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This content explains the concept of enzyme inhibition, detailing how inhibitors decrease or block enzyme activity, and explores various types of inhibitors, their mechanisms, and their significant applications, particularly in drug development and medicine.
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so ladies and gentlemen you are all
welcome to my YouTube channel in today's
class we are going to look at the
concept of enzymes inhibition and uh
ladies and Gentlemen please if this is
the first time you are coming to my
YouTube Channel Please Subscribe and I
hope the class will actually
uh be of important to you and uh please
try to subscribe and join my YouTube
membership Community where you'll find a
lot of other interesting
videos and this PowerPoint as we can see
is not made by me it's made
Dr assistant
for so uh let's start with the lecture
so when we said an enzymes inhibitor
enzymes inhibitor so when you said
enzymes inhibitor we know that generally
enzymes is a molecules that
comvert the molecules that convert
substrate to product and enzymes is a
molecule that convert and enzy is a
molecule that convert a substrate so a
substrate here stand for S so enzymes
plus substrate will give partical and
enzymes substrate complex which will
later give us a free enzymes plus the
product so this is how enzymes catalyze
reaction so in a situation where you
have an inhibitor so an inhibitor is a
compound that usually decrease or uh
diminish the rate or velocity of an
enzyme catalyze reaction by infuencing
The Binding and O is turn over number so
generally enzymes inhibitor or an
inhibitor is a ules that when bind to an
enzymes is
decrease or block the activity of the
enzymes completely so it can either
decrease the activity that is the
velocity of the enzymes
or completely deactivate the enzymes
activity so that is what you call
enzymes inhibitor so it's a molecule or
it's a compound that when bind to the
enzymes it can either decrease or diminish
diminish
the velocity of the enzymes or the turn
over that is how speeds when you said
velocity it means house speeds the
enzymes is catalyzing the substrate to
product you can have the situation where
you can have an enzymes maybe
in one micro minute in one micro minute
maybe the enzyme is converting 100
substrate to product but in the presence
of an inhibitor the activity or the
velocity of the enzymes may be
decreased by maybe instead of converting
100 substrate to product it will end up
of converting maybe five substrates to
product so it means that the activity or
the turn over number of the enzymes is
decreased by the inhibitor so that is
what we call an inhibitor so this
inhibitor uh actually classified into
organic so it can be organic the
inhibitor can be organic or it can be in
organic so these are the actually class
of inhibitor it can be organic that is
maybe it's D from organic molecules or
it is an inorganic so
uh one very interesting things that we
should understand is that the enzymes
the enzymes can be sorry the inhibitor
can be trops like in so many cases in so
many cases most of the drugs that we
produce and the pharmacy IAL industry
there are Inhibitors of enzymes so uh
that is why understanding the knowledge
of uh inhibitor and enzymes is very very
essential in the area of Pharmacy and
medical Sciences because with the
knowledge of enzymes and enzyme
inhibition you can be able to develop a
new drugs for a particular disease and
also in addition so many drugs so many
drugs are enzyme inhibitor like for
example uh we have like Anin combating
enzymes it's an enzymes that produce
anint one unj tens two and anint tens
two is a constrictor so actually anint tensin
tensin
enzymes com enzy is an enzymes that is
associated with hypotension so if you
can get any mo that can block or that
can diminish or decrease the activity of
an converting enzy
to prevent conversion of an one to 2 it
means that the molecules can serve as
antihypertensive drugs so that is why
you need to understand that if you are
able to understand the enzymes they the
the the what the enzymes is actually
catalyzing and the products what are the
importance of the products that are
catalized by the particular in a system
is very very essential so if you're able
to do that if you are able to know that
them from there you will know whether
the enzymes is a very good Target in
terms of Dr design Discovery so it is
very very important to understand that
so many enzymes so many enzymes
Inhibitors there are drugs so that is
why as a student of medical Sciences you
need to understand the importance of the
Inhibitors try to understand how the
Inhibitors are what are they meant for
it is very very essential
and in addition some of these enzymes
they are some of these enzyme inhibits
they are antibiotics of course when you
said antibiotics remember there are
molecules that are actually involve in uh
uh
killing microorganisms especially
bacteria so antibiotics are the
molecules that
kills microorganisms so it cure disease
that are ass assciated with the
infection and of course remember that
some of the bacteria they are classified
as positive and gr negative bacteria so
the major molecules that actually
protect the
microorganisms especially bacteria from
any AAL attack is the pepti glycon that
is found on the cell of the bacteria so
there are some enzymes that are imported
in actually biosynthesis of fog glycan
on the wall of the on the cell wall of
the bacteria so there are so many
antibiotics like for example fyin and
pin there are drugs that inhibit the
enzymes called
transas the transes is one of the key
enzymes and the synthesis of
plycon so of course pheline is an enzyme
that inites the activity of transes and
as a result of that glycine cannot be
produced so iFly cannot be produced it
means that the solell of the bacteria
will not be actually built you canot the
cell will not be produced as a result of
that the microorganisms will die so we
should understand that some of the
antibiotics that are available in the
market they are enzymes Inhibitors and
of course some of the Inhibitors they
are toxins at what stage or at what uh
State can we consider an enzymes to be S
an enzyme init to be a toxins maybe that
is a particular enzyme that is very very
important for the survival of human like
for example let's just let me just give
a s an example of let's say aalin aalin
is an enzymes that actually degradate
aalin asalin is a neurotransmitter that
help in the transmission of information
between other part of the body to the
brand so if you can get any molecules
that can inhibit the activity of AAL so
what will happen it means that estalin
cannot be actually degradated to produce
the product which actually help in the
uh transmission of information between
the body and the brain so if you are
able to actually or if there is any
component can inhibit the activity of
those enzymes it means that it is a
toxins because it blocks an enzymes that
is very essential to the survival
of living organisms of a human being so
that is where we should understand that
like in so in so many cases let me just
give our examples of uh of some of the
anti some of the
toxins like for
example there is what you call uh
uh
uh incde some of the
insecticides they are toxic so if human
take them like for example like is a
insecto side that is called Pia so it's
an insecto side that if you take it it
will block the activity of some
important essential enzymes in human and
that is why it can lead to the death of
human so we should understand that some
of these Inhibitors they are
antibiotics then in addition the next
thing that we are going to look at is of
course some of these inhibitor they are
antimetabolites they are antimetabolites
what is antimetabolite when we said
metabolite there are molecules that are
involved in the metabolisms of
uh of some uh food product that we are
taking so you said antimetabolite it
means that there are molecules that
prevent the body to utiliz the metabol
that in the body some of them they are
natural products of enzymes reactions so
these are actually some of the
Inhibitors that are found in humans and
also their classical groups so some are
drugs some are antibiotics some are
antimetabolites some are natural
products so uh that is actually enzymes
Inhibitors enzymes Inhibitors it means
that there are molecules that prevent
the enzymes or that slow down the
activity of an enzymes or in some cases
it can even completely block the
activity of the
enzymes so then uh let's now look at the
types of enzymes Inhibitors so enzymes
Inhibitors are divided into three we
have one we have reversible inhibitor so
you said reversible Inhibitors it means
that it's a stage where or a types of
inhibitor where if the inhibitor is
removed from the enzymes the enzymes can
still continue with it activity like for
example if you have the inhibitor
let's say you have the inhibitor you now
have the enzymes plus the inhibitor so
when you have the
enzymes when you have the enzymes plus
the inhibitor to give us enzymes
inhibitor it means that at this point
when you have an enzyme inhibitor
complex it means that that is the the
substrate cannot bind so but in a
situation where the Inhibitors is
removed you will have your three enzymes
then plus the inhibitor then the enzymes
will actually uh go back and convert the
substrate so it means that it's a
reversible because when the Inhibitors
Inhibitors can be removed and the
activity of the enzymes will be restored
so that is
reversible enzymes inhibition and we
have two types of reversible enzymes
inhibition we have what we call
competitive inhibition we have non-c
compettive reversible enzymes init and
we have on
on competive
competive
enzymes inhibition so these are actually
three types of RS inhibition and then
the second other types of enzymes
Inhibitors we have a RS so you said
irreversible enzymes inhibition it means
that there are molecules that once they
bind to the enzymes then it means that
the enzymes will commit suicide the
enzymes will actually will not longer
reverse to not restore it is activity
because it is the Inhibitors is binded
to the enzymes using the calent process
but in the case of reversible
inhibitions why the enzymes actually
Resto it activity is because the binding
between the substrate and the inhibition
is using a noncovalent forces like
hydrogen bonding Bond force of
attraction and electrostatic so that is
why the Inhibitors can be removed and
then the enzymes can restore it is
activity but in the case of irreversible
because the inhibition between or The
Binding between the enzymes and the Inhibitors
Inhibitors
is using calent bonds so as a result of
that it is very very difficult it is
very very difficult to remove that types
of inhibitor from the enzyme so that is
why it is called suicide
Inhibitors and then the next time of
enzymes inhibition is allosteric so
generally enzymes they have other site
apart from the active site so we call it
aleric site so aleric site is a site
where the Inhibitors combin and
inactivate or activate the enzymes so
but in this case we are thinking about
Inhibitors so enzymes have aleric side
where the Inhibitors bind and then
decrease or block the activity of the
enzymes so uh this is actually these are
the types of the enzymes inhibition so
now we are going to look at them one
after the other so starting with actually
actually
reversible inhibition so in IR
reversible inhibition here the inhibitor bind
bind
noncovalently so that's why it is the
Inhibitors find noncovalent so you said
noncovalently it means that the
interaction is a weak interaction so
noncovalent interaction as I said from
the previous slide it can be hydrogen
bonding it can be Bond because of
Attraction it can be electrostatic force
of attraction so the Inhibitors V
noncovalently with the enzymes so if the
inhibitor is removed then the action of
the enzymes will be fully restored so
when the enzymes when the Inhibitors are
removed then it means that the activity
of the enzymes will be fully restored
to so generally an equilibrium is
established between the free inhibitor
and enzyme substrate and enzymes
inhibition complex and is defined by an
equilibrium constant and the equilibrium
constant is Ki which is called
inhibition constant so we have enzymes
plus substrate then we have enzy
substrate complex so generally an
equilibrium is established between the
uh the the free Inhibitors and the
enzymes of complex and of course the
activity of the enzymes is fully
restored on removing the Inhibitors by
dialysis so with just a simple dialysis
you can remove the inhibitor from the
enzymes active side because the
direction is very weak so
um so now let's look at of course the
types of enzymes inhibition so the types
the types of reversible enzymes
inhibition so we are starting with
competive so from the the word
competition it means that of course
there is a competition and of course the
competition in the case of this reverse
gr enzymes oh sorry competative
inhibition is between the inhibitor and
the substrate because the substrate and
the inhibitor they look alike like for
example now let's look at this this is
the enzymes this is the enzymes and this
is the substrate so look at the
substrate here
look at the inhibitor so if you look at
it clearly here you can see that the
enzymes and Inhibitors they look alike
so therefore the enzymes if the enzymes
is binded with the substrate then of
course the enzymes substrate complex
will be produced which is this and then
of course the free enzymes will be
generated and then finally the product
will be form but in the case of uh this
inhibitor when inhibitor bind to the
enzymes so there will be no catalysis or
it may actually decrease the catalysis
of the enzy and one very interesting
thing that we should understand that
inhibitor bind
reversibly the same site that the
substrate bind to so the inhibitor is
bind to the active side where the
substrate bind to and compete with the
substrate for The Binding so the
inhibitor is actually a substrate analog
it closely resembles the
substrates so it can be actually
reversed by increasing the concentration
of the substrate so uh one very
interesting things that we should
understand in these types of compettive
inhibition this if you have the
substrate and the inhibitor in the same
in the same
same
environment so
what will
determine whether the substrate will be
the one to find or the inhibitor so at
that point actually the concentration
matters if the concentration of the
Inhibitors is higher than the
concentration of the substrate then the
inhibitor will bind to the active
sides but if the concentration of the
substrate is higher than the
concentration of the inhibitor then the
substrate will B and then catalysis will take
take
so that is what happen
so of course this one is another example
so this is the inhibitor this is uh look
at it here this is an e this is the
substrate and this is the competive
inhibitor so you see in this case the competive
competive
inhibitor bite but of course here
increasing the concentration of the
substrate here by looking at how the
concentration of the substrate increase
here look at it here we have one
inhibitor one substrate so that is where
the inhibitor B but in this case we have
the concentration of the Inhibitors to
be very high so after increasing the
concentration of the inhibitor then the
sorry the concentration of the substrate
then the substrate will now removed it
will now remove the subst the inhibitor
and then the substrate will bind so that
is what happen that is how the
inhibition revers is is actually
reversed by increasing the concentration
of the substrate so of course here after
increasing the concentration of the
substrate then the inhibitor was
actually removed and then the substrate
pil so the degree of inhibition depend
on the concentration of the
substrate depend on the concentration of
the substrates and on the relative
affinities of the enzymes for
substrate and the inhibitor so you
should understand that actually in this
point or in this uh in the case of this
competitive inhibition concentration
matters a lot concentration matters a
lot if the concentration of inhibitor is
higher than that of the substrate then
the inhibitor will B but in the case
where the concentration of the substrate
is higher than that of the uh of the uh
of the the inhibitor and the substrate
will now bind so uh that is this so This
is actually a brief discussion on the compettive
compettive
inhibition so now let's look at how the
compettive inhibition work so you see in
this point we have an Appo enzymes which
is an active enzymes so we have the
substrate and we have the inhibitor so
substrates with B to the enzymes and of
course there will be an enzymes product
formation where the product will be
generated but now here look at it here
we now have inhibitor so the inhibitor will
will
now bind so if the inhibitor bind to the
of course active site then it means that
there will be no catalysis so this is
another example this a compettive
inhibitor and this is the prod and this
cells so we should understand that in
the presence of inhibitor because the
enzymes and the substrate are sorry the
enzymes and the inhibitor are conf for
the same poet or the same active SES so
this is actually what happen so the concentration
matters so now what happened if you have
a competative inhibition what happened
to the kinetic par parameters what
happen to the kinetic parameters so
generally in the presence of compettive
Inhibitors velocity generally
decrease the velocity generally decrease
you see this is the velocity decrease
therefore the effective concentration of
enzymes is
reduce and of course the km is increase
so remember that ladies and
gentlemen the lower the km the higher
the inity of enzymes toward the
substrate so if the km value increased
it means that the uh activity or the
Affinity of the enzymes toward the
substrate also decrease so this is what
happens so because km is increased then
the Affinity of the enzymes toward the
substrate is apparently decreased in the
presence of the inhibitor but V Max is
not affected so you should understand
that the kinetic parameters
in enzymology is KM and Vmax so in the
case of compettive inhibition Vmax
doesn't change it doesn't affect the
Vmax that is the maximum velocity but km
is affected by increasing it is
concentration so this is actually a
graphical presentation of
uh a graphical presentation of competive
inhibition so you see here this is using my
my
M you have the parabolic shaped
shaped
graph so this one no Inhibitors and this
inhibitor so it doesn't affect the V
Max but of course look at the km so the
km in the absence in of Inhibitors look
at it here it's very low but in the
presence of the inhibitor is increased
so this is the new km when the
substrates when the Inhibitors fine when
the absence of inhibitor is low so the
lower the concentration of course the
higher the Affinity of the m so but of
course we know that we this is a line w
box representation of the competitive
inhibitor of course in the presence of
inhibitor look at what happened but look
at the point where we have the P Marx
nothing ch
there is nothing change also here look
at it nothing change so that is the V
Marx it doesn't affect it here also look
at it where there is inhibitor and no
Inhibitors they still meet at the same
point so V Marx it doesn't affect it but
of course look at it here in the absence
of inhibitor look at the VX here sorry
km and also in the France of in look at the
the
K so you should understand that the Vmax
it doesn't change in the case of
competive Inhibitors but the
velocity of the Vmax sorry the km it is
actually increased thereby decreasing
the activity of the enzymes toward the substrat
substrat
so let's look at example here this is
malonate so malonate is a competive
inhibitor of su de hydrogenous
enzymes so we have of course the enzyme
is an enzyme that is an enzymes in
citric acid cycle
where the enzymes combat Sate to ferate
so the malonate here is an example of
competitive inhibitor
of suat so look at it the only look at
the structure of the subate and M and and
and
Bon it they looks similar they look very
similar so in the presence of this
inhibitor it will block the activity of
the suin the hydrogenous therefore the
suin will not be converted into
fate so look at actually this is
the enzymes so the enzymes is
here and this is the substrate and of
course we have subate enzymes complex
and then we have fumate was the but in
the presence of melanoid
melanoid
malonate the enzymes B to the malonate
and of course the activity of the
enzymes will be blocked therefore there
product to be produced so that is in the
inhibition so Al this is another example
antibiotic action of sulf drugs that is
sulfonamides it has a structural analog with
with
FL FL that is para
see the the enzymes
called teroid synes is an enzymes That
comat Power Plus 78
dihydro dihydro teric acids produce
folic acid and you know the importance
of folic acid it is very very
important in uh in developing baby during
during
Francy so the major enzymes in in the
par synthesis of folic acid and that is why
why
sometime because folic acid is very very
important especially during Francy so
generally you see that fragant wom in
some cases they are supplemented with
folic acid because it is needed for the
growing babies
so this power
power
plus 78
dihydro acid is converted into folic
acid in the presence of theid
entities but in the presence of the sulf
that is sulf it is having a structural
analog with the fiber with the F that is
amzo acids so it will now
bind with
the enzymes
therefore it will now inhibit the
bacterial enzymes so this is actually in
bacteria in bacteria the synthesis of
folic acid is in bacteria so but it's
not to humans human cannot synthesize
folic acid so generally human in human
we cannot synthesize folic acids so we
don't have these enzymes but if you want
to kill bacteria you can use the
sulphonamides to inhibit these enzymes
who can prevent the synthesis of folic
acid so as a result of that it will kill
hum so soorry it will kill the bacteria
so because we in humans we like these
enzymes that is why the sulfur drugs
will not affect us it will not affect us
because we don't have
enzymes and then so these are the
example of clinically
useful compettive Inhibitors that are
for disase treatment for example we
have STS an example of this St we have
example of this St we have
have
aob we have
have
Simas so they actually the Inhibitors
they are compettive Inhibitors that's
Target an enzymes called HMG Co reducts
and they are trtic use they actually
have to decrease plasma cholesterol
level and also it has antiy liid
agents so it reduce
the so another examples of uh this uh
Inhibitors we have uh
alool so we have
alool which also inhib which Target an
enzyme antin
oxidase so of course this alol because
stin Ox is one of the enzymes that
involve in the degradation of uh U uh
and the degradation of nucc acid to
produce uh uric acid and you know that
theout disease is associated due to
accumulation of uh due to accumulation
of uric acid which is the end product of
nucleic acid so using alool is a
competive inhibitor ofin oxidation that
use in the treatment of C disease and
you also have metet which is also a
competive inhibitor of dihydrofolate
reductors which also used in the
treatment of cancer and there is also
cup we have C we have C we have cup C to
and and and AF which is also uh a
competitive Inhibitors in Anin
converting enzyme so it inhibit Anin
converting enzymes which is used in the
treatment of high blood prev that is
hypertension remember that actually from
uh the previous slide we I actually
discuss about this so and combating
enzymes foru V constrictor which is an 2
so these are some of the Inhibitors or
drugs that are used to inhibit the
activity of the enzymes which actually
have lowering lowering blood frion we
have we have diomal which is also uh
init vitamin K epoxide redu enzymes and
used in the treatment of
anti-coagulant ser as
anti-coagulant so uh
this is actually examples of some drugs
that are comput Inhibitors and the
enzyme that they are targeting and their importance
importance
in the D in disease
treatment so um the next thing that we
are going to look at is a non-c
compitative inhibition so in the case of
non-c compitative Inhibitors in this
case the enzymes is not actually binding
to the active site the Inhibitors bind
at a side older than the active side of
the enzyme so it's not binding at the
to so in this case in the case of this
uh non-c compitative
inhibition the inhibitor it has no
structural resemblance to the substrate
so there is no structural resemblance
between the uh substrate and the
inhibitor so no comp competition for
binding so in this case there is no
competition for binding and of course
increasing the concentration of the
substrate it doesn't
relieve this inhibition it doesn't
relieve the inhibitor from Bing the
active side so the inhibitor and the
substrate bind at different sides and
therefore in this case the enzymes
combind to the substrate and as well as
the inhibitor to produce enzymes
inhibitor substrate complex so it's
possible to produce both enzymes in hio
complex and enzymes in hibo substrate
complex it is possible to produce both
the two so the enzymes inhibition
inhibito substrate complex
forms product at a slower rate than
enzyme substrate complex so therefore it
will slow the reaction very low
therefore the rate will be very low when
the inhibitors
to the sub string so the reaction is
slot but not Haled it usually not heed
it usually not block the reaction
completely rather it slow it it's it
slow the reaction very well so you see
this is actually the other site where
the Inhibitors bind and this is the site
where the substrate will
bind so therefore there is no
competition in terms of the ACT side
between the inhibitor and the
enzymes so uh then the next thing is of
course still under inhibitor so you see
this is the enzymes and this is the this
is where we have the inhibit this is the
inhibitor this is the substrate so this
is the enzymes active sides this is the
inhibition binding s so of course here
we can the substrate combined to produce
an enzyme substrate complex and will now
have the product but a situation the
enzymes substrate complex you can have
the enzyme substrate complex and then
the inhibitor at the same time bind to
produce the
enzymes substrate inhibition complex so
the product is formed at a slower rate
but not halted and you can also have a
situation where the Inhibitors will B
PRS like this and Then followed by the
substrate so you can have the two
cases so you can either have the
Inhibitors first bind to the substrate
or the substrate will first bind before
the inhibitor bind so you can have the two
scenario so what happened to the kinetic parameters
parameters
so in the case of KM the km remain
unchange so if the km remain onchange
then it means that the inhibitor do not
interfere with The Binding of the
substrate to the enzymes and the Vmax
decreases therefore the inhibitor cannot
be overcome by increasing the
concentration of the substrate so this
is what actually
using the
mement graph that is hyperbolic you see
this is the km this is the km so the km
it doesn't affect it the km doesn't
affect it and of course the V Marx
change loc at here it changed so as you
have as you have the Inhibitors the Vmax
change in the case of nonc competive
Inhibitors look at also using the line r
box plots you see that the km remain the
same it remain the same look at it here
and then the V marks change with the
inhibitor and with no inhibitor the V
Marx change so that is what happened in
the case
inhibitor so non comp example of non-competitive
non-competitive
Inhibitors we have heavy metals like for example
example
silver ion merury ion and Lead ion and
cile
sh of the enzymes that is in the the [Music]
[Music]
Sile T grow of the enzymes and then we
also have P which also
in which actually non competively
inhibits fsin we have inhibitor we have
ethanol or narcotic drugs that
inhibits acid
phosporus nonc
competively so this is actually what
happened in the case of non-competitive
inhibition so the next one is
uncompetitive inhibition so what
happened in the case of uncompetitive
inhibition in this case the inhibitor
bind only to the enzyme substrate
complex not to threee enzymes but you
see in the case of non-competitive
Inhibitors the inhibitor can bind to the
free enzymes and it can also bind to
enzyme substrate complex but in this
case uncompetitive
inhibition the Inhibitors usually V to
enzymes of complex not the free enzyme
and the inhibitor cause structural tion
it change the structure of the active
side of the enzymes so therefore the
enzymes become catalytically inactive
then the inhibitor can't be revised by
increasing the substrate concentrations
since the inhibitor doesn't compete with
the substrate for the same binding SES
so the inhibition of like for example
the inhibition of placental alkaline
phosp that
is call it enzymes
enzymes
by Alin so look at it this is an enzymes
so first the enzymes bind with the
substrates and then the substrate will
now bind soon so the inhibitor will now
bind to enzyme substrate complex so that
is why it is called uncom ination so
after the inhibitor B then it will now
distort it will now change the structure
of the enzymes active
sites so this is what happened you see
this is an enzymes so we have an enzymes
and the substrate so the enzymes first
look at it here the enzymes first but
the substrate then we now have enzyme
substrate complex and then we now have
the inhibitor and then the inhibitor
will now binds so after
that we now
have enzyme sub inhibition inhibitor
complex so in this case we have enzy
substrate and then we have enzy
substrate complex from the inhibitor
then we now have enzyme sub inhibition
complex so in this case the Vmax
decrease the km decrease then inhibitor
has no affinity for free enzymes it
doesn't have Affinity to free enzymes so
you see the km change both in the line w
box and the M menting graph the
km the km change and the VX change so
both the two change so that is what
Inhibitors so then the next thing that
we are going to look at is the
irreversible inhibition so irreversible
inhibition is the types of inhibition in
which the Inhibitors Vine covalently
with the enzymes so it is usually a
reversal so it can it can't dissociate
from the free enzymes it cannot
dissociate from the enzymes after
binding to the uh to the enzymes because
the bonding is very strong so the
inhibitor cause confirmational change at
the Active side of the enzymes
destroying their capacity to function as
a catalyst so once they inhibitor once
the reversible inhibitor B to the
enzymes cently it will now change the
conation of the enzyme active side
thereby it will now completely destroy
the enzymatic activity of the enzyme so
the catalysis of the enzy will be
completely dissociate and the enzy
activity is not reg as
dialysis or by increasing the substrate
concentration and of course a variety of
poisons such as
iodoacetate Organo prosate poisoning and
oxidizing agent act as a
inhibition so let's look at what happen
in the case of irreversible inhibition
in terms of the kinetics irreversible
irreversible
irreversible is similar to non compitative
compitative
inhibition where the V Marx decrease and
then the km no change there is no change
in km so you
see the km here Remains the Same but in
the presence of inhibitor look at what
happened in the absence of inhibitor the
Vmax change so Vmax change in the
presence of the
inhibit so these are the examples
of the irreversible Inhibitors we have
dium which actually uh
inhibits alides de hydrogenous and is
used in the treatment of
alcoholism we have cite which actually
uh inhibit cytochrome oxides and this
one it inhibit respiratory change so
when that is where we have cide
poisoning cide poisoning can even lead
to the dates a particular individual
because it affects cytochrome oxid which
is a key enzymes in respiratory so once
this enzymes is inhibited there will be
more energy no energy would be generated
and of course as a result that if
the care is not taking a person will die
there is a fuite also inhibit an and an
is the key enzymes in glycolysis so
therefore the glycolysis will be
inhibited so we have so many of them
here we have the iso profile
fluorophosphates which actually
inhibites serin protasis and acetal
estal acalin EST
and they are Ser as enough gas so these
are actually some of the example of
inors they are
function so then the next one of course
is suicide inhibition so it's a
specialized form of a with inhibition
also known as mechanism based Activation
so it make use of enzymes on reaction
mechanism to
inactivates to inactivate it so in this
case the inhibitor of a structural
analog a structural analog is converted
to a more effective Inhibitors with the
help of the enzymes to be inhibited so
the enzymes literally commit suicide
they utilize normal enzymes reaction
mechanisms to inactivate the
enzymes that is in the case of Sude is a
specialized form of irreversible
inhibition but in this case the
inhibitor use the course the enzyme's
own reaction mechanisms to activate the enzyme
enzyme
itself and of [Music]
[Music]
course in this case the enzymes
literally commit suicide
suicide
because they utilize normal enzymes
reaction mechanisms to inactivate the
enzymes these are the examples of the uh
suicide inhibitors
aspirin al alool
alool
Five Ur and of course these are the
products and these are the enzymes that
they targeted and these are the
example the suicide Inhibitors the help
in the treatment of
chosis also non
nonsteroidal and inflammatory drugs
cancer and
gouts so then the next thing is altic
inhibition so what is aleric inhibition
so generally enzymes have old
sides apart from the active SI so that
other site we call it Al aleric sight so
you see some enzymes possess additional
site other than the active site and the
site is called an aleric site e site
that is AIC side of our enzymes and they
are unique on o molecule so these aleric
effectors they are the substances that b
the aleric side and regulat the enzyme's
activity so in this case we can have a
positive althetic
effectors so if the positive althetic
effectors in this case the enzy
activities is increase so once the
molecule bind to the aleric side will
increase the activity of the enzymes but
we have a negative allosteric activators
or effectors what they are doing is when
this negative allosteric effectors B to
the active site then it will now inhibit
the activity or it will now decrease the
enzym activity and in the case of aleric
enzymes when the
altic uh molecules bind to the altic
side of the enzymes then the Shi of the
graph will change from the normal
molic Shi graph to give sigid C graph so
this is actually what happened in the
case where the inhibitor is not a
substrate analog and it is a Fally
reversible so when excess when excess
substrate is added then it will now
reverse The Binding and then the km is
usually increased and then V Max is
decreased in the case of aleric
Regulation so when an Inhibitors B to
the aleric site the configuration of the
active side is modified such as such
that the such that the substrate cannot
bind properly and as a result of that we
will now get a sigmoidal shift that is
how the sigmoidal shift of the
enzymes is
generated so you see km is increased and
V Marx is reduced you see the km here if
you look at the km
here you see in the absence of the
inhibitor and in the presence of
inhibitor look at how ites and then the
V Marx also decrease in the presence of the
the
inhibitor so
that is what happened in the case of
at how it works so we have active SES we
have the enzymes and we have the aleric
site so these the enzymes in the enzymes
we have active site and we have
allosteric site so when the allosteric
inhibitor bind to the active side bind
to the aleric side then it now distorts
the configuration of the active side of
the enzymes and as a result of that this
is the distorted active site then of
course the substrate will now bite so
the molecules can be altic regulators
and can be altic inhibitor so you see in
this case this is where we have
allosteric inhibitor so once the
inhibitor bind then it will now distort
the active side of the enzy so as a
result of that the activity of the
decase so these are the examples
of the
aleric examples of the allosteric
molecules you see here in this case we
have glycolysis the fat we have
glycolysis TC in the glycolysis we have
phosphorus one and the inhibitor that
bind to the aleric side of the one
a TP and citrate and the activator is a
positive aleric activator is so this is
how we have the Inhibitors and the
activators the enzymes they actually
activate or deactivate and the
pathway so let's look at the example you
see this is a phosphate where it's converted
converted
toose Six B phosphate is an enzym
callus one so you see uh the enzymes
here this is the catalytic subunit of
the enzymes and this is the Bing side
and this is the
inory subunit of the enzymes and this is
the EMP binding site so you see
here ATP is a
negativity and then m is
POS so the P of pfk is quary protein and
has two alic regulator side and a active
side so the two altic Regulators one is
for the activating and one for
inhibiting so you see here ATP in it is
regulatory binding side you once it CL
then it is this is a in inhibitory sub
unit and this is the activating sub unit
so The Binding side for the substrate
presently and impossible pit to the
catalytic activity has been lost because
once this ATP is actually binded then of
course the active side of the enzymes is
distorted so nothing the subet cannot
bind so it means that we lose the
activity of the enzy so now let's look
at this in this case look at it when we
have EMP bind so you see The Binding
side for the substrate presently and
excellent pamp form an excellent pit
when B and of course there will
be full catalytic ability of the
enzymes so that is actually for the
allosteric sit and then we also have
what you call uh feedback negative
feedback inhibition and end
product inhibition so there a
specialized type of aleric inhibition
and this is ired to control the
metabolic fat ways for efficient
cellular function so you said end
product of a metabolic reaction produced
in excess so when the end product of a
particular metabolic reaction is
produced in excess so it inhibit the
first regulatory enzymes in the Su so in
the end product inhibition we have a
situation where the Cod of a particular
like for example in glycolysis the end
product of glycolysis is ATP so when
this ATP is built off at the end then it
will now come back inhibit the first
enzymes of the glycolysis like for
example in glycolysis we have 10 enzymes
and the end product is ATV so when ATV
is producing enough enough it will now
come back to inhibit
the face enzymes or the regulatory
enzymes like for example in glycolysis
we have three regulatory enzymes so if
the n product of glycolysis which is ATP
inhibit the activity
of the enzymes the first enzymes or the
regulatory enzymes so that is described
as n product inhibition or negative feedback
feedback
inhibition so like for example let's
look at this
so in the negative feedback let's say
this D is the end
product and you see because it is the
end product now it's built up then it
now come back and actually inhibit the
face enzyme so that is what happen in
inhibition so these are actually
that end product ination we have him
which is the end product and the enzymes
to be inhibited we have all synthes and
the part is him synthesis we have
cholesterol which is the n product and
it meet HMG Co do which is the first
enzymes or the key enzymes in
cholesterol biosynthesis and the f Way
the pathway is cholesterol synthesis so
these are the some of the example of end
product that it repeats the face enzymes
or regulatory enzymes and the part way
are so this is actually uh some basic
comparism between all the
tree so all the form all form of the
Inhibitors all the form Inhibitors this
is just the summary so you can just look
at the summary and understand what how
one differ from one another as we
explained like for example in the
compettive inhibition the structural
similarity there's a structural
similarity between the inhibitor and the
substrates but in the case of nonmutated
inhibitor there is no structural
similarity and of course in the case of
irreversible inhibition the inhibitor
bind tightly to the enzymes by calent
Bond then in the case of althetic the
inhibitor B to the althetic side of the
enzymes and then the for the suicide
inhibition then the inhibitor make use
of the enzymes on reaction mechanisms to
inactivate it but for the end product
inition then the end product inhibit the
earlier enzymes of the fat so this is
just the differences between
them so now let's look at the importance
of enzymes in evion number one it's
helpful understanding the regulatory or
the regulation of
enzyme activity within the living C with
the living cells and it is also usable
in elucidating the cellular metabolic
fats by causing accumulation of enti
also it help in identification of the
catalytic or the functional GRS and the
active side of enzymes it also provide
information about substrate specificity
of enzymes it is also useful in to study
the mechanisms of of catalytic activity
and the enzymes Inhibitors after a f
application so DRS useful in medicine I
feel to be I feel punction by inhibiting
a certain en so most drugs are competitive
competitive
Inhibitors are competitive or suicide
Inhibitors so ladies and Gentlemen
please if you didn't join to my YouTube
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