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Welcome, we just finished today the part belonging to the enzymes, which can be motivated by
the presence of the Vanadium.
So, how vanadium can get inside the cell, how vanadium can show some interactions with
different important biological
processes. So, basically today will be talking about the interaction of all these groups
related to the vanadium; so the part 4 of
Vanadium Enzymes. And if we consider some of these as the model compounds, because the
particular active site, what we can
have in the biological system. So, if we have the active site in the biological system,
and some of these positions having some
useful donor atoms, like nitrogen, like oxygen or any other useful group, which can be identified
by different techniques like,
structure or other spectroscopic signatures. So, how a particular active site can go for
the vanadium interruptment and how the vanadium can go for several important
reactions, which can also be mimicked in the laboratory by synthesizing some related model
compounds. So, the synthesizes and
characterization of these model compounds, play some important and interesting role in
understanding several important aspects
related to vanadium chemistry. That, if we just simply consider whether this active site
is participating or catalyzing some
important reaction where electron transfer play some important and major role.
Then we should have a related model compound, where the environment the coordination environment
compared to the active
site environment, where definitely these groups are the immediate donor atoms, which are bond
to the metal center, the metal ion
center. But in case of model compound these are the useful donor atoms, can be nitrogen,
can be oxygen and how this particular
donor atoms can be a part of the ligand system; it can be a part of the ligand system.
And when the metal center is not present that means, several other oxygen, oxygen or nitrogen
donor atoms may be available
there, may not be originating from the same ligand system; that means, the same proteins
backbone. But some other small groups
can enter over there, where the same passage of the metal ion that means, the passage of
metal ion as vanadium can also be
studied very nicely. So, is model compound plays some vital and important role, in understanding
the type of chemical reaction,
which is being catalyzed by these vanadium centers, for electron transfer or some atom
transfer reactions. So, if it is an atom transfer, so we can also
see the same atom transfer reaction with the help of these model compounds. So, one
such example for that is that, when these model systems can have some water as the ligand.
And if water is occupying a position
which is correspondingly trans to the oxo group, which is important for the labialization
from the strong trans influence. So, we
have chosen one such system, which is reported in the literature also, that if we have these
backbones, as a saleslady high
backbone with bromine substitution to the para position of the phenol oxygen. And which
is being condensed with one mole of
glycine, so we get very simple O A, O N O tridentates ligand.
So, this is one part of the cavity, what we are just talking about that this particular
part is available for coordination of the
vanadium. So, if the system the cell can par meet, the entry of vanadium center to this
particular part. So, vanadium can go and
immediately form three bonds, one is this vanadium oxygen, second is this vanadium nitrogen,
and third is this vanadium oxygen
bond. So, the same is also true, when vanadium is bond to this particular ligand system in
a typical coordination compound. So, what happens there that immediately depending
upon the major of the vanadium salt, what we are using over there,
immediately this vanadium is coordinated to this tridentate ligand. So, the binding of
this tridentate ligand is very important, so
model compounds we can have from the choice of this ligands, so first of these is a simple
tridentate ligand. So, why we are
taking this particular tridentate ligand is that, we have this oxygen nitrogen oxygen
binding, and vanadium is forming three bonds
to that. And we will we do not know what other positions would be, and what are these positions
will come and bind to the
vanadium center. So, this particular phase is it is tridentate to vanadium, and two more
positions are occupied by two other
groups which are unknown, which can be x or which can be y.
So, this particular species that means, x and y you already know all this thing that,
x can be our very good substrate species, so
when this ligand bond system that means, the vanadium is there, and ligand was already
present there. So, depending upon that
these V L species can have two to three positions vacant, it is not vacant in the true sense,
it can be occupied by water molecules,
which is present in the system. And which is already there when vanadium is bond to
these water molecules to give us the
corresponding ACO compound. So, these vacant sites can go for bending this x and some other
reagent this y can be our reagent. So, there are positions where the substrate
can bind to directly to the vanadium center, the reagent can also bind to the vanadium
center. And in the next step, these two that means, the reagent and substrate can react
to give rise to our product. So, product is
formed from there, so very important thing is that how this tridentate ligand is binding
to the vanadium center. So, we all know that depending upon the flexibility
of the ligand backbone, we can have two different types of binding, one is
meridional binding; that means, this three can bind to the vanadium and they are in the
same plane. So, when they are not in the
same plane, the same tridentate ligand occupy one particular phase, so if they occupy one
particular phase, we call these as a
corresponding facial binding. So, the choice of ligand is therefore, can dictate us whether
we should take a corresponding
tridentate ligand, which can bind in meridional fashion. Or the same tridentate ligand, which
can go and bind the metal center in
the facial mode.
So, in this particular case, what we see that, this particular ligand as well as the other
ligand, where we have some different part
of the glycine derivative. We have some alcohol part also to check whether, this vanadium
has higher affinity for this carboxylate
oxygen; this is the carboxylate oxygen or it has some binding affinity to the alcohol
oxygen. So, when you get the compound,
when you synthesize the compound, and characterize the compound. We can identify that vanadium
has more affinity for the
carboxylate oxygen, rather than the alcohol oxygen.
Because, these to have different p k values, and the basicity of the remaining oxygen,
what is getting from there as O minus has
also different, so vanadium will have direct affinity for binding to the carboxylate oxygen.
So, when these three positions are
blocked in a meridional mode, we can have three other remaining positions. And these
three remaining positions are interestingly
shifted over there, that if we get the immediate vanadyl-oxygen. Because, vanadium compound
very easily formed the
corresponding vanadyl complex, it is directly coming from the oxygen of the water molecule
also. So, initially if we have the
vanadium water bond, then after deprotonation, it goes to vanadium hydroxide; and then finally,
to vanadium oxo bond. So, when oxo is there, and if we just see
that three of these are coming from the ligand, fourth is also another aqua molecule. So,
initially when this dotted water molecule is not present, we have a situation, where
the geometry of the coordination environment
can be considered as a square pyramidal one. So, if this particular vanadium oxygen bond
is not so short, and if we cannot have a
corresponding pyramidal distortion of the geometry.
This water molecule can come opposite to that of our vanadium center with respect to the
oxo group, and quickly start interacting
with the water molecule. Similar thing also happens this is compound number 5, where this
vanadium instead of water
coordination, it can bind to some alkoxide anion. So, this is an ionic coordination and
also during hexa coordination, it has some
weak coordination from the water molecule trans to that of our vanadium oxygen double
bond. So, this particular occupancy that means,
why this water molecules should be there or not that is being dictated by the oxo group.
So, this particular presence of this oxo group, if it is not transforming from oxo to hydroxide
or hydroxide to aqua molecule. This
oxo function can weaken the corresponding vanadium oxygen bond coming from the water
molecule trans to this vanadium
oxygen double bond. So, what we get that we can make these compounds
in the vanadium plus 5 oxidation state. So, initially what we get if we the
your ligand is tridentate dinegative in this form, this ligand, this L if we can have charge
on this oxygen, and charge on this
oxygen, we can have a corresponding compound of the ligand, where L is giving rise to two
negative charges. So, vanadium is
there, so we can have 2 negative charges from the ligand, and also since it is coordinating
with the oxo, so vanadium oxo can also
2 negative charges. So, immediate neutralization of 4 negative
charges by vanadium 4 plus. And if it goes for one more step towards oxidation, it can
go to vanadium in 5 plus oxidation state, so modeling of this particular oxidation state
is very easy. And we can have the
corresponding vanadium pentavalent compound that means, vanadium in plus 5 oxidation state.
If we can have NO 4 donor set,
in roughly trigonal bipyramidal coordination geometry, so what should be the most preferred
coordination geometry. So, instead of this particular square pyramidal
or octahedral geometry, the info O donor set, here also we can have 3 oxygen, and
to 5 oxygen anion. So, this is an NO 5 donor set, this is also NO 5 donor set for an octahedral
geometry around this vanadium as
well as on this vanadium. But if we can have a NO 4 donor set around the same vanadium
center, it can distort itself to a
corresponding trigonal bipyramidal geometry, which is a preferred geometry, for this particular
vanadium center. And we also see we can compare this vanadate
groups or vanadate anions to that of our phosphate. And the phosphate anions
will see in case of phosphate is hydrolyte reactions that this vanadium center will have
some preference for trigonal bipyramidal
geometry, compared to square pyramidal geometries. So, here the this particular labialization
that means, the presence of
vanadium oxygen bond, how they are weakening the corresponding vanadium water group can
be seen. If we determine the corresponding single crystal
x-ray, structure of this synthesize compound in a good crystalline form. And
determination of these vanadium oxygen bond this particular bond, this dotted bond we
find that the corresponding bond distance
for this vanadium oxygen bond, lies in the range of 2.28 to 2.35 Armstrong, which is
clearly a bigger value a longer value. Where
we see that the normal distance falls in the range of 1.98.
Because, within the same system we can have another bond which is this particular vanadium
oxygen bond, which is cis to this
vanadium oxygen double bond, but this bond is pretty shorter in the range of 1.98 Armstrong,
compared to these bond, which is
in the range of 2.35 or 2.28. So, this particular bond is pretty weak, and when substrate comes
and bind this particular centre it
immediately can displace; these two positions that means, either these two water molecules
can be replaced. One can be considered as the binding of x
the substrate and another can be bond as the corresponding reagent, for the usable
transformation centre at the vanadium site.
So, interestingly also that this particular vanadium complexes, if they go for some amount
of interaction, what we see that already
we have this vanadium oxygen double bond, and we can have other groups. So, if the plane,
the square plane is formed from
three other donor atoms, one is nitrogen and two oxygen, and this other oxygen. So, if
five positions are occupied, and if one of
these positions can be taken up by the corresponding substrate molecule.
And we see that this particular centre having some vacant site that means, this particular
area or this particular space is very
important such that, we can consider a corresponding binding of peroxide anion. So, we have seen
large number of vanadium
compound, whether it is in the living organism or in some model compound that vanadium is
forming a corresponding peroxide
bond. In this particular fashion that means, in cis mode and it is forming a very tight
bonding pattern for a three membered ring. Because, this is a corresponding three membered
ring for the corresponding coordination of both the oxygen atom, instead of any
such bridging type of coordination involving two vanadium centers. So, we can have these
and this particular group, basically this
peroxide compound which has a corresponding charge of 2 minus. So, the vanadium peroxo
compound is very important. This case, and we should have sufficient vacant
space such that, the peroxide anion can go and bind to vanadium in this form. So,
once it is bond we have this oxygen and this oxygen, so we need further stabilization.
So, if possible that means, this particular
linkage is not very much stable, compare to our oxo binding, oxygen binding or nitrogen
binding. So, to stabilize this particular
peroxo group to the vanadium site, we need some other type of interactions which can
stabilize the enter vanadium peroxo
fragment.
So, what is that, we see that in this particular case, this vanadium peroxo group, and we already
know that it has two negative
charges, so some residual delta negative charges are there, which is present on these oxygen
atoms. And if we have some group
attached to this ring of the ligand system that means, if we have some ortho NH 2 function,
so this NH 2 groups if they are
available. So, when it forms corresponding complex, this NH group is in close vicinity
to this particular, and it can form some
hydrogen bonding interaction. So, through such hydrogen bonding interaction, this particular
vanadium peroxo species can be
stabilized. And that also give us some important information,
that if this particular group is your reagent, and if this particular vanadium
peroxo reagent can show some hydrogen bonding interaction on the substrate molecule. Then
this particular substrate can be
reacted towards this activated peroxo anion, which is bond to the vanadium group. Similarly,
not only the NH 2 function of the
ligand system, but simple water molecules. So, if we have water molecules as well as
protons present in the systems, like that of
our pyramidal structure of the ice molecule. So, one water molecule over here, which is
already hydrogen bonded to another molecule of water. And we can have the
corresponding proton either this is bond to this carboxyl function, so if the carboxyl
function which is already bond to the
vanadium centre, have instead of O minus group it can have the OH function. And this OH function
can be stabilized by this fast
water group of these water dimmers. So, this is the water dimmer which is getting stabilized
through hydrogen bonding through
internal hydrogen bonding between two water molecules.
And this oxygen further shows hydrogen bonding interaction with the OH group of the , and
the peroxide linkage showing some
other type of hydrogen bonding interaction which is different from compound 9. That means,
this hydrogen is forming interaction
with both the two oxygen atoms of the peroxide groups, so it is a different type of stabilization
of the vanadium peroxo unit. So,
not only this stabilization helps this particular entity, but it also helps the presence of
the OH function or the carboxyl end of the
ligand. Because, in the long polypeptide chain on
the protein chain, we can have several of such OH groups attached to the polypeptide
backbone, it can be originating from the amide backbone or it can be originating from the
corresponding carboxyl backbone. So,
these backbone hydrogen atom available on oxygen or nitrogen, if it is amide can further
be stabilized in the presence of water
molecules. And these water molecules can further interact with the peroxide to stabilize this
vanadium with respect to that of our
peroxide link. So, we call these interactions, these hydrogen
bonding interactions we all know that these interactions we call as non covalent
interactions. So, non covalent interactions are beyond the molecular interaction, so we
call them as the corresponding
supramolecular interaction. So, we have the vanadium compound is one molecule, and then
we can have some other part of the
species like this NH 2 or the water molecules, coming from the separate water molecules it
can be present in the system as the
lattice water molecule. Or some other water molecules which is trapped
within the crystal lattice for that, so this interaction with the ligand periphery
that means, the peroxide functions are present at the ligand periphery. Because this particular
part is blocked only the part which
is available for this hydrogen bonding interactions is that site where the peroxide linkage is
coordinating to vanadium. As already I mentioned that, if we can have
some vacant space or vacant area in this particular area, then only the peroxide can
show this sort of coordination to the vanadium centre, and which further shows hydrogen bonding
interactions with the water
molecules. So, hydrogen bonds in all these complexes plays some important role is stabilizing
the entity, where we can have the
direct coordinate bond between vanadium and the peroxide anion. So, these peroxide groups
we can have, so in this particular
entity where we can have the corresponding vanadium, as the corresponding vanadium oxo
function, and the peroxo function, so
we can consider this as vanadium oxo peroxo species.
So, if we can go for some reaction, where we want to study the corresponding oxo transfer
reaction, we can see that this
particular oxo group can be transferred to some other substrate. So, substrates should
be there, and we can transfer the oxo group
to the substrate, in some cases if we have the species which is a composite of both the
oxo group, as well as the peroxo group. We
can see that whether this particular oxygen atom is being transferred from vanadium centre,
from this oxo end or from the peroxo
end. So, several of these reactions, these peroxidase
activity we have seen, which has been obtained, in case of vanadium chloro
peroxidase, vanadium bromoperoxidase species where the vanadium peroxo group is interacting
with the corresponding Cl minus
and Br minus, which is found from the marine origin.
So, if we consider the same oxo transfer reaction to bromide that means the bromoperoxidase
activity. Or if we just consider the
corresponding oxo transfer reaction on the sulfide group, we can see that they are all
catalyzed by the oxo vanadium species
through some hydroperoxo intermediate. That means, initially if we can have a non oxo
vanadium compound, that non oxo
vanadium compound can be transformed to some oxo vanadium compound.
And that oxo vanadium compound can interact with hydroperoxides, forming the corresponding
stabilization of the peroxide unit.
Either the neat peroxide anion or the protonation of one end giving the hydro peroxide unit,
which is originally started giving us
through the hydrogen bonding interaction of the peroxide anion to some hydrogen bond donor.
So, what we see that this these
particular corresponding transaction state, where now the vanadium is present in a trigonal
bipyramidal geometry, not in some
square pyramidal geometry or octahedral geometry; but it is present in a typical trigonal bipyramidal
geometry. So, all these species are very important that
means, if we can have this nitrogen, we can have these as one donor atom, and
another is to this site, but also if we have the simple nitrogen atom from the protein
chain. And this particular position can be
occupied by simple hydroxide group, this is oxo group, this is a second hydroxide group,
and this is O, this is the third hydroxide
function, and it can go for deprotonation giving O minus.
So, if they react with hydrogen peroxide, what happens that when hydrogen peroxide is
bond to the vanadium centre, this
position of this nitrogen getting changed, it is coming from this particular position
is occupying, this particular OH group. And
nitrogen is over here this oxygen O minus is moving over here, and one new water molecule
is coming over there, and this has
been converted to a corresponding vanadium oxo function. And which is trans to this particular
water molecule that we have seen
just now. That the labialization of this water molecule
in a typical octahedral environment is due to the presence of this vanadium oxygen
double bond or the vanadium oxo form. So, from a trigonal bipyramidal geometry, we move
to a octahedral geometry, because
this particular bond is little bit squeezed one, and this we can also consider as a one
bond. So, if we consider this as one bond, so
which is the trigonal plane and these are the two sites for the trigonal bipyramidal
geometry. Otherwise, we can consider if these two are
considered as two bonds, this can be considered as a typical example of octahedral
geometry. So, when we put some proton that means, this particular peroxide anion is getting
protonated, and the centre what is
generated over there is our vanadium oxo plus hydroperoxide anion. So, this not the simple
peroxide anion, this is now the
hydroperoxide anion, so this hydroperoxide anion is useful to react, so this is the most
reactive species. And this reactive species is basically responsible
for interacting with the substrate group, if the substrate is the bromide anion
which can supply this particular HO group, this is the giving you HO Br species. So,
OH group is coming from here, and this
peroxide group due to this particular reaction is going back to this oxo hydroxide species.
So, peroxide species is therefore, no
longer will be present over there, so this peroxide group is getting consumed over there.
And we have the corresponding transformation of Br minus to HO Br. Similarly, this oxo
can transfer to the sulfide group R 2 S,
so sulfide group is also taking this HO plus species. That means, this particular part
of the peroxide, hydroperoxide unit giving rise
to this immediate attack on the sulfur. And finally, to the sulfoxide formation, so that
we know that how we can transfer this
oxygen atom to simple dimethyl sulfide group, to form the corresponding dimethyl sulfoxide.
So, dime reducates reactions we already know that dime, so reducates type of reaction where
the sulfides are getting transformed
to sulfoxides, can also be seen through this sort of reaction where vanadium is interacting
through a vanadium oxo peroxide unit.
Therefore, the presence of all these three groups that means, the presence of this nitrogen,
presence of this oxo group, and the
presence of these peroxide linkages are important for the reaction, where we transfer this HO
plus unit to Br minus or S R 2 unit. So, if we just consider what is this nitrogen,
if this nitrogen we can consider that the corresponding immune nitrogen of the ligand
system in the model compound, or this nitrogen can be considered as a corresponding enzyme
nitrogen of the histidine, and the
nitrogen function of the model compound. So, the presence of this nitrogen is crucial,
and which is important. Because in all these
cases, whatever species we are getting in the form of the oxo hydroxo species, which
is reacting with the substrate molecule is all
these cases not only the vanadium oxo peroxo unit is present, which is all the time bond
to the nitrogen. And this nitrogen is coming from the enzyme
histidine or it is coming from the immune group of the nitrogen ligand. So, all these
vanadium oxo peroxo species, we have some unique nitrogen donor atom, so this is therefore,
crucial for all these compounds, we
can have the specific nitrogen donor, which can control the reactivity, And these nitrogen
can come from the enzyme also, and
this can also come from the model compound.
So, what we see next that, some of these vanadium compounds can show some insulin like effect,
so the concern condition where
insulin is responsible for glucose metabolism is very important. And this particular biomolecule
can handle can tackle the
corresponding degradation of glucose molecule, in the case of glucose metabolism reaction.
So, the effect of this insulin can be
mimicked, if we consider some vanadium compound, some important vanadium compound can be a
good substitute of this
particular insulin compounds by showing some insulin type of effects.
So, what we know that in this particular case, the action of insulin which is responsible
for our carbohydrate, and lipid
metabolism in our body, when insulin is enactive in our body is not interacting. We can have
some diabetic condition that means
the insufficient carbohydrate metabolism and lipid metabolism, so action of this insulin
molecule is important. And how it is
acting on this carbohydrate or lipid molecule is that, during this interaction a syringe
of signaling processes are taking place. That means, when insulin is entering into
the system, it can give rise to some signaling process; and that signaling process is
responsible for the assimilation of the glucose or the carbohydrate molecule to the system.
So, basically this particular insulin is
interacting with the insulin receptor system, so there are some receptor sites and those
receptor sites are useful to bind this insulin
molecule, and this insulin goes and interact with these insulin receptor site.
So, if we can have some equivalent vanadium compound of that nature which can function
as insulin, so, these vanadium
compounds can have some property of interacting to these receptor sites. So, that we see that,
some of the vanadium compounds
which are of very special type, and we can choose these vanadium compound from a large
number of such vanadium compounds,
varying from one particular ligand system to the other.
In this case, these vanadium compounds show some insulin like effect and therefore, can
show some enhancement of the effect
of insulin by two step things, one is the phosphor relation of the insulin receptor.
Because how this particular molecule that
means, the vanadium compound which is a synthetic compound, coordination compound of vanadium
can go and interact with
the insulin receptor through the corresponding phosphor relation state.
And in some case it can inhabit the protein phosphatases that means, the proteins phosphatases
are responsible for phosphate
hydrolysis reaction. And if we are able to inhabit or stop the corresponding hydrolytic
reaction of these phosphatases, we can
consider that these vanadium compounds are useful in inhabiting the phosphatases activities
on the phosphate extract groups. So,
therefore, this action of insulin is directly related to the corresponding interaction with
the insulin receptor, and vanadium
molecules with some interacting sites which we have seen. In that, it can interact with
some site, where it can show some
hydrogen bonding interaction, in a similar fashion this synthetic compound can show some
interaction with that of our receptor
site.
So, we can see that very simple compound that means, the vanadium sulfide not a complex,
metal complex, so vanadyl sulfide is
the corresponding typical inorganic compound where we have the vanadium oxygen group. So,
we have the vanadyl function, so
vanadyl function is present and therefore, in this particular case this V O is present as 2 plus. And in this particular
case also what
we have seen in the compound, where we have the corresponding ligand environment this
was our ligand. So, you have the ligand environment, and in
this ligand environment we have the same vanadyl unit is present. So, this is a bigger
molecule or rather complex molecule, and if we consider that this should go and pass the
cell membrane to entire into the cell to
show some interaction, which is similar to that of our insulin molecule. Before that
if we just consider that the simple vanadyl
compound where the vanadyl sulfate. So, we can check whether the vanadyl sulfate with
V O 2 plus unit, can interact to the
corresponding receptor site for the insulin molecule.
So, when we use vanadyl sulfate, we see that the simple vanadyl sulfate can show some glucose
control activity with some people
or it is on the experimental animals, like rat it can experimented on some rat to see
that the type two diabetes can be controlled
by the simple interaction with the vanadyl sulfide molecules. So, that gives rise to
the typical medicinal applications of these
vanadium compounds, so in vitro and in vivo studies both inside the cell, and outside
the cell. We can study the corresponding activity for
glucose control of these vanadium compounds of two different types of patients; one
is type one diabetic patients, and another is type two diabetic patients. In the formal
case they have the corresponding insulin
deficiency that means, their pancreas cannot produce sufficient amount of insulin to control,
the glucose metabolism, and in the
second case it has some insulin tolerance. So, both this two types can be seen whether
they can show some affect, if we use vanadyl sulfate as a medium for controlling the
glucose. So, they can stimulate the glucose intake into the cell, so how we can go and
we can put the glucose inside the cell, so
glucose should enter into the cell; and then we can go for the degradation of the glucose,
and thus it can lower the corresponding
blood glucose level of the diabetic patients. So, these diabetic patients have high blood
glucose level, and this high blood glucose level can be counter acted, if we can take
the glucose inside the cell, and we can go for the metabolism. And in this process it
can thus interact with the glycol genesis, and
glycogenolysis, so in this two cases which is also related to lipogenesis where the lipolysis
are hydrolyzed. So, all these hydrolysis
reaction that means, the glucose hydrolysis reaction, and the lipid hydrolysis reaction
can be controlled by the simple
administration of vanadyl sulfate. So, some of these sites can be activated, and through
that activation we can see that, it can
show some corresponding mimetic reactions.
So, insulin the molecule which can produce in Langerhans’ islets or pancreas, so there
are some site where pancreas is responsible
for the production of insulin, and basically this is a peptide hormone. And it has a typical
organic molecule only having a peptide
backbone only, and which regulates the glucose and fatty acid or the lipid metabolism. So,
insulin is responsible for both the
glucose and fatty acid metabolism, and if we can have shortage of insulin we cannot
see the corresponding control of this glucose
metabolism. So, this is a typical flowchart for several
of this complex reactions, and where we see that the signaling cascades we have
considered that during this particular interaction, it shows some signaling pathway. So, signaling
cascades are important, and
where we have the phosphatester bond which is responsible for showing that signaling
process. So, in the first step in figure a that
means, this part of figure which shows that, this is our insulin molecule, so this hormone
is coming and within the cell membrane
it is coming and this is our receptor site. So, this particular part is the extra cellular
part and this is the intra cellular part. And this particular part is responsible to
put this
particular glucose molecule inside the cell, so when this insulin coming and sitting comfortably
on the receptor site, and receptor
site has some tyrosine part which is very important. And this tyrosine part which is
basically responsible for showing this
particular receptor site, whether this phenol group this is the OH function. Whether this
OH function is phosphorelated or not that
basically gives us some information, whether this insulin can come over here.
And whether this particular gate, this is a gate for the entry of the glucose molecule
from the extracellular site to the intracellular
site, so in this particular case this PTP is nothing but protein tyrosine phosphatases.
So, PTP that is Protein Tyrosine Phosphatases
is the corresponding enzyme, showing the corresponding phosphatase activity. That means, if we have
the oxygen phosphorous
bond of the phosphate ester, the PTP can interact with these and can break this oxygen phosphorous
bond showing the phosphor
hydrolysis reaction. So, this phospho ester reactivity can be seen,
if we can break this particular oxygen phosphorous bond, so during that process
when we have this oxygen phosphorous bond, it shows the corresponding signal pathway.
And this signaling pathway can open up
this particular gate and this through this particular path we basically this arrow shows
which is nothing but the transport reaction
path. So, basically this path when the gate is open insulin is sitting over here, so when
the gate is open the glucose molecule can
come and enter through this gate. So, here was the glucose, here in the figure
a, so in figure b we have the glucose molecule which is entered in the extra intra
cellular a region, and this particular one molecule when it is entered within the cell
system can go for the corresponding burning
process that means, the glucose is metabolized. So, glucose metabolism can only take place,
where we can have this particular
glucose molecule inside this particular cell. So, this PTP basically, this PTP then if it
can walk on this oxygen phosphorous bond
can responsible for this corresponding metabolism. So, insulin basically giving us some information
that when insulin seats over there, the gate opens up and glucose can enter inside
the cell. So, in the figure c, where we see that the insulin is not there the gate is
closed, and the PTP, if the PTP is available the
PTP can work on this and which can click the corresponding ester bond, so the PTP is active.
And the activity of the PTP is
responsible for the breaking of this oxygen phosphorous bond, giving rise to the corresponding
tyrosine unit, tyrosine that means,
the bearing the phenol group, and the phosphate anion.
So, this situation we do not like, so if this situation is there we require the insulin
to come over here to open up the gate, so if PTP
is active it should break the corresponding bond, and if this bond is no longer there
the signaling cascade is stopped. So, what
happens that if we have some vanadium compound, see the vanadium compound is there and which
can pass through the
membrane. And this vanadium can go inside with some modification which is curly bracketed
vanadium, and which is square
bracketed vanadium. So, some modification on the vanadium compound
can take place through it is passage through the cell membrane, and this
vanadium can interact with the PTP. So, the enzyme PTP is now interactive with the vanadium,
and this vanadium compound can
be considered as the corresponding phosphatase inhibiter. So, this phosphatase inhibiter
that means, this PTP molecules will no
longer be utilized for breaking this OP bond of the phosphor ester.
So, OP bond is will remain intact, and it shows the corresponding signaling process
that means, it can produce the giving the
signal to open up the corresponding gate. So, in absence of insulin only the presence
of this vanadium, which inhabits the
corresponding activity of the PTP. So, the gate is opened up and the glucose molecule
can enter inside the cell, and can go for the
corresponding metabolic pathway that means, the glucose molecule can be metabolized producing
carbon dioxide and water
molecule. So, this vanadium compounds therefore, showing
the same effect what we have seen, in case of the presence of the insulin
molecule, only thing that it basically inhibiting the corresponding action of this PTP molecule.
So, this PTP if we can go for the
corresponding inhibited design for that, so we engage this PTP with this vanadium, so
it is no longer available for the hydrolysis
reaction. So, insulin mimetic behavior, we can see from
this vanadium compounds and the entire scheme basically what we have discussed
just now, can represent simplified is very simple form of signal pathway, which is induced
either by the insulin or by the
vanadium. So, this path, this dotted line this dotted line the signal pathways can be
seen only, when we have insulin in our system
or we can have the corresponding vanadium compound within the system.
So, if we have the cell membrane, it contains the trans membrane receptor for insulin, and
which is basically the corresponding
tyrosine kinase. So, this tyrosine kinase is responsible for insulin docking, an insulin
is docking is nothing but insulin is coming
and sitting at the receptor site of the insulin, and tyrosine is getting basically phosphorelated
and in during this phosphorylation it
gives rise to a complicated signal transduction cascade.
So, the dotted line what we are showing in the previous scheme is that, it is basically
a corresponding signal transduction cascade
pathway. And this phosphorylation can be counteracted, if the PTP which is responsible for the hydrolytic
rupture of the
phosphoester bond that means, the phosphatester hydrolysis reaction, and during this phosphatester
hydrolysis reaction, the signal
process is taking place. So, this particular hydrolysis reaction is
fully effective in absence of insulin or in case of insulin tolerance, so how we can control
this hydrolytic reaction, so we bring the vanadate; so the vanadate can come and enter
the cell via some phosphate and sulfate
channels. So, these are not some receptors sites, unlike the insulin molecule, insulin
need some receptor site through that receptor
site insulin can enter the cell, but in case of vanadium these are the phosphate and sulfate
channels, which are very important
channel sites. And through those phosphate and sulfate channels,
vanadate can enter into the system, and through that entrance the vanadate
inhibits the phosphatases, and one such mechanism is that inhibition of PTP by vanadate only.
And which allows the
phosphoester bond, and thus the signal transduction to remain intact, the signal transduction
should remain operative which
allows the gate to open, and which can bring the corresponding glucose molecule within
the cell for glucose metabolism. So, that
is the basic function for all these vanadium compound for glucose control, and which is
showing some corresponding insulin
mimetic activity. Thank you very much.