Hello. So, today we will start from electron
transport proteins. In the first part we will
deal about some of the important
molecules, which are basically iron containing
proteins. So we will have iron containing
proteins, and we will think about the
functional role, basically which is very important
to know how iron is functioning therefore,
a different type of reactions. So we
will think about the functional role of the
central metal ion; that means the iron.
So, in all these molecules, it can play one
part as a structural role, and in some other
places what we have discussed earlier that
these iron containing proteins also function
as, storage and transport. And next is what
we will be talking today, is electron
transport, which we all know they are very
important molecules, cytochromes. So they
are present within the cell, which we all
know that they are the cytosols, and they
are very much colored; that means, they have
some chromophoric part, which is
responsible for color absorption, so they
are our cytochromes. And also we know their
function in dioxygen binding, in
hemoglobin, and myoglobin molecules. And we
will discuss little bit about their catalytic
function, which is also very important;
therefore, they are large and diverse in nature.
So, the main backbone of all these molecules,
are our prophyrin molecules. So, we will have
the porphyrin in the system, so the
heme proteins we all know. So, this porphyrin
molecules, they are giving rise to a four
nitrogen atoms to the iron center, and this
particular name has a origin for the Greek
word purple; the strongly colored. So, invisible
spectroscopy also helps us, the
presence of the cytochromosine fat. They have
been determined first, by knowing the corresponding
characteristics spectra of all
these molecules.
So they are all the porphyrin presents, and
which is a basic part of it, and this prophyrin
as the single unit as the perol, and we
have the tetra parole unit. So this tetra
parasol unit will get, so it has different
substitution positions. So, depending upon
the
different substitutions, they are of different
types, that we will see afterwards, but at
the same time, when people discovered
these molecules an interesting molecules for
the different activities, and one of them
has been identified as the protoprophyrin.
They have the typical nomenclature for their
different substitution, and some time they
have the historical origin also. So, when
this particular backbone have four methyl,
two vinyl, and two propionic acid; that you
should little bit remember, that what are
the different substitutions, because these
substitutions play some important role, while
we talk about some heme proteins, or
some heme b proteins in hemoglobin and myoglobin
and the cytochromes. So, when these substitutions
we have we get a heme b
molecule, and when people made this molecules,
they are also interested for laboratory synthesis.
So, we all the time you can
have, the corresponding molecule in the laboratory,
you make the molecules and how the meddle
complexes in this taking place,
in presence of the iron that people can compare.
So, this is also very simple reaction of four
molecules of petrol with respective aldehydes.
So when you use formaldehyde you get
CH2 designing; otherwise we can have also
some substitutions at these positions, so
all these positions can be occupied by this
R
CHO. So this particular basic unit it will
we can have. So, we have the four nitrogen’s
and these two have hydrogens only. So,
basically we get a ligand which is LH2 type,
so you have two nitrogens having, where in
protons and those two nitrogen’s can go
for the deprotonation, while it is complexing
with the iron center, when we gave for the
good for the corresponding heme protein.
So, this particular unit when we get. So,
we know already that, we get the heme proteins
when the ligand is here porphyrin. So, it
a microcyclic ligand. So, that porphyrin which
is coordinated to your iron, then one class
of molecules we will talk about which is
cytochrome p450. So, they are also heme containing
group of enzymes. So, there are some kind
of enzymatic reaction they can.
So, an enzymes then we all know how the different
metal ions can change the molecules. So, the
same porphyrin can be used, for
coordination to magnesium. So, when porphyrin
coordinated to magnesium. So, this particular
ligand is very useful to give you
chlorophyll. Then for one another type of
microcyclic in we get, which is one sort one
carbon sort or analog which is known as
corroles in vitamin B 12. So, we will have
the corroles which is present in vitamin B
12. So, it has one carbon sort of system,
so
one carbon shorter analog.
Then we have another group of molecules known
as corpins c o r p i n s, which is present
in cofactor f 4 30. So, which is highly
reduced porphyrin, but now it is coordinated
to nickel, and nickel is showing presence
of this microcyclic ligand corpin. A
important reaction which is present in the
active site in methyl co enzyme m reductase,
which is required in methane producing
bacteria, and is the last day for the production
of methane. So, in this the background when
we have, the four peroll units, and
four peroll units are connected to each other
and they give some implant coordination; that
means, when it is connected to iron,
you have four implant coordination which has
satisfied by four nitrogen in it, and another
group of molecules people have tried
and synthesized in the laboratory, which is
known as phthalocyanine, and here we get some
of these carbons substituted by
nitrogen.
So, they are known as nitrogen substituted
porphyrin. How they are substituted in the
back bone, what we have we have seen
that we have that methelene connector. So,
you have the peroll unit on the one hand,
and another peroll unit in the other hand.
So, basically some time also during the ligand
synthesis we can connect two peroll units
by a methylene or methine bridge, but
when these are substituted by nitrogen. So,
nitrogen and this double bond so these molecules
are known as therefore,
phthalocyanine people have tried to make all
these molecules, and their reactivity with
the different metal centre people have
tried, because all the time when we try to
give the compound, until and unless we make
the compound nicely and go for the
structural determination, we always relay
on the spectroscopic thing.
So, spectra will always compare. So, if you
have the model compound, and some of this
cytochromes or hemoglobin or
cytochrome p, p for pitied type of molecules.
We always try to compare those spectra with
the molecules compounds, and then
try to say that this has this environment
and that is giving some important reactions,
related to that iron centre, because we are
not going away further or far away from the
iron centre. So, what are our cytochromes.
So, ligand has been defined, or identified
that we have this particular ligand environment,
and within that ligand environment, as
we know from our knowledge form hemoglobin
or myoglobin type of molecule, that we have
the iron centre, and in most of these
drawings we will see that this is your porphyrin
plane. So, here heam the other form the plane
of this porphyrin rings, only this
particular part is available, and then we
have the fifth coordination site, and the
six coordination site. So, when we have these,
then here it is connected to some emmiter
jole side chain, emmiter jole side chain of
some of the long protein chain, which is in
this particular case is histidin 18. So, this
particular environment we all know that this
was present in the myoglobin molecules.
So, you have four coordination sides coming
from the microcyclic porphyrin ring, and the
fifth form the histidine emitter jolie ring
and this particular side six side was available
for binding to dioxygen molecule, but in this
particular case this is also connected by
methylene sulphur.
So, metheninin group we known that, amine
acid residue from the metheonine is s methyl
group then you have the c h two and c
h two function. So, this is methonine 80.
So, all this six coordination sides are fulfilled.
So, you have a nice octahedral iron centre,
and that iron centre will be responsible for
our electron transport. This will be responsible
for electron transport, but what is the
difference between these, with that of our
heme protein which is present, or the heme
is group is present in that myoglobin or
hemoglobin molecule that we can see, that
in this particular case, we have that iron
center, and this iron center is bound to four
nitrogen’s of the porphyrin ring. It is
very easy to draw, because we draw the four
porphyrin ring, and then we connect it, so
have
the unsaturation the positions. So, you have
no choice for the different substitutions
what we have seen, that we can have the
substitutions.
So, these are the positions. So, you have
one two three four five six seven eight, eight
positions for the different substitutions,
and
we basically number it, starting from this
carbon. So, if this is one, the next is two,
this is three. Then four five six seven eight
nine ten eleven twelve thirteen fourteen fifteen
sixteen seventeen eighteen this is nineteen
twenty, after this point twenty, then
this nitrogen is numbered as twenty one, second
nitrogen is numbered as twenty two, third
is twenty three, and then twenty four.
So, all the positions we have numbered. So,
numbering is very important, because most
of the cases, because the different types
of cytochromes if we say the a cytochrome
a cytochrome b cytochrome c d etcetera. So,
we will talk about only the substitutions,
because all these substitutions play some
important roll, particularly their (()) how
they bind and their corresponding shapes also.
So, when this particular cytochromes are there.
So, you have one is the methyl substitution
at number two, then you get
something, what is that sulphur. This is methyl,
this also sulphur, this is this is CH2 CH2;
that means, the propionic acid function
we all know, form the hemoglobin and the myoglobin
molecules. So, this is also a propionic acid,
and this is CH3, see if we just
simply recall that what is our heme b system?
In heme b system the upper porphyrin ring,
these two are different; the upper one,
this one and this one, those were having methyl,
as well as on the right hand side you have
the final substitution. Here it was
methyl but this your final substitution. So,
what is happening they are now, this is the
only difference with that of hemoglobin and
myoglobin molecules; that now you have a protein
chain. So, protein chain is coming close to
the porphyrin ring, and it has two
cystenal residuals, and those cystenal residuals
are attaching, or attacking rather to the
final ring, so final substitution.
So, you have a thioether linkage direct thioether
linkage with the protein chain. So, now your
porphyrin ring in your hand and that
is now embedded within the protein chain,
how the protein has only the castle residuals.
So, correctly disposed cystenalsulphur
residues what they are, and those are reacting
with this final group and this final group
. So, these two final groups are attacked
and you get a strong protein chain, and that
protein chain attached to the porphyrin ring.
So, what is the difference with that
molecule, is that cytochromes, the protein
varying two sulphur ends now covalently attached
to the microcyclic ring, which is
your porphyrin ring; that means, it is the
activity pattern and all the other things
will be completely different to that of your
myoglobin and hemoglobin molecules. So, this
particular one; that means, you have these
four groups from these, and you have
the fifth and the sixth positions from the
hystedine as well as the mythelene sulphur.
Now you have a typical octahydral
molecules in your hand, and that octahedral
molecules will basically give to us some electron
transport chain in mitochondria. So
we have mitochondrial electron transfer chain.
So mitochondrial electron transfer chaininvolving
our cytochrome. One molecule will study is
your cytochrome c. So, there are
large number of molecules. That basically
the difference between these is only in the
porphyrin chain. So, basically this is very
important chain, will start from some biological
using agent nicotenamyde and nelucotide in
the oxidized form. So, you have n a d
plus we write, and the other form is n a d
h it is a reduced form. So, so at one end
you have this then you have flavoprotein.
These are all biological reductance, so this
flavoprotein will then transfer the electron
to cytochrome b, then to 
cytochrome c 1 to
cytochrome c. So, there we have the cytochrome
c, where it is. So, these up to this point
we get that cytochrome. So, cytochrome
c what will use it has some important role
to play in the electron transfer chain in
the mitochondria; that it accepts electron
form
cytochrome C 1 and donate the electron to
some other molecule which have known as cytochrome
c oxidase, why these are
known as oxidase, because these are the responsible
for oxidizing your cytochrome c. So, on the
right hand side what we get. So,
it has high potential.
So, the cytochromes c oxidize can function
as an oxidizing agent, for your cytochrome
c, and it is a very complex molecules, little
bit we will see afterwards, that how cytochromes
see bearing iron beaingprophorineplay some
important role to oxidize
cytochrome c. And lastly this will end up
in dumping electron to O2 for our respiration.
So, the mitochondrial respiration what we
use, and we bond our glucose material or any
other food material. So, you bond this material;
that means, the glucose material,
with the help of your dioxygen molecules.
So, ultimately these dioxygen molecule is
accepting four electrons, and dioxygen
molecule will be converted to water molecule.
So, this is a long chain, and this particular
long chain, will see the different steps,
depending upon the difference in the corresponding
e zero values; the redox potential values.
So, all these molecules will have a
typical e half values. So, we have a characteristic
e half values for all these biological molecules.
So, those who are on the right hand side,
should be able to oxidize the species on the
left, because you know that this is the
strongest possible oxidant in your hand, and
some where here above this N A D plus, we
have the glucose molecule. So, glucose
is getting oxidized by your dioxygen molecule,
but we are not allowing this dioxygen molecule
directly, to react with the glucose
molecule; otherwise that will be a binding
process, so in a stepwise manner, depending
upon this electrons transfer chain.
So, this chain is required, such that you
can have in a stepwise fashion oxidation of
these glucose molecules or any other food
material by the dioxygen molecule, and depending
upon the difference in your differ e zero
values, we have the corresponding
required amount of free energy change at these
reactions, and those free energy change for
this different reactions, will be
utilized for our A T P synthesis. So, the
basic goal for getting all these things that
how we use the cytochrome c, and how this
cytochrome c is useful for all these reactions,
to produce our different amount of A T P molecules
for our energy purpose.
So, this interesting class of molecule, the
cytochromes are first discovered by a man
which is C A McMunn, you should know
little bit about the history, it is not very
old molecule, it was discovered in 1884 only.
Then the total characterization was made,
and people proposed that it has a corresponding
porphyrin ring or the iron ring, is done by
another man who is David Keilin, what
he did. He has a handmade spectroscope. So,
here has to relay on , the determination of
the spectral behavior, or the spectral
property of all this molecules. So, porphyrin
rings what we have seen, they have a very
strong and characteristic absorption
spectrum, and that characteristic absorption
if we are able to monitor. So, we have through
these handmade microscope, sorry
microscope we have the characteristic absorption,
and these characteristic absorption are known
as soret bands.
So, whenever there is a porphyrin in a system,
so in all the biological fluid or in the biological
liquid sample. If we suspect that
there is a cytochrome molecule; that means,
the porphyrin ring is there. So, we must detect
the corresponding solid band in to the
system, because in all these electron transfer
molecules involving there, they are responsible
for different types of oxidation, and
reduction reactions, because those reactions
are responsible for our very survival; that
means, respiration, how we utilize
dioxygen molecules for this respiration. So,
this particular system has, when we are getting
the characteristic absorption band. So,
we will get three different types basically
in that nature of the heme group. So, cytochrome
a we can have, cytochrome b we can
have, and as well as cytochrome c, and they
are first characterized in yeast cells.
So, these nature of these corresponding porphyrin
ring will tell us, that if we have a b type
cytochrome present, which is nothing
but a protoporphyrin nine. Just now I told
you that it would be protoporphyrin some numbers
is also tagged with it protoporphyrin
nine, and which is also present in hemoglobin,
same porphyrin, the porphyrin is also present
in our hemoglobin molecules. Then a
type cytochrome is a different one, with regard
to that of our substitution, and in this particular
case, we have a hydrophibic tail
of isoprene group. So, we have the isoprene
tail is present, plus a formyl group, in place
of our originally present methyl
substitutions. So, nothing is changing there,
only the substitution is changing from one
to the other. Then we have the final group
attached porphyrin nine for cytochrome c,
and we have a covalent.
Now the difference is that already we have
seen, that it has the final groups found,
present in the ring covalent bond, covalent
thioether bonds, with whom, with cysteine
residues of the protein. cysteine residues
of the protein. So, they all present, and
everywhere, not only in the mitochondria,
so they are known as basically the electron
transporters, who are responsible for
transporting electrons. So, they are basically
electron transporters, have already seen that
they are present in mitochondria, they
are also present in chloroplasts, then endoplasmic
reticulum, and different bacterial redoxchain
as well. So it is not only present in
the human system, is present in plant origin,
it is present in bacterial origin also. So,
in bacteria also they play the redox transfer,
so in bacterial, redox chain. So, we have
now iron centre, which is satisfied from its
all coordination demand; that means, they
are
all hexa coordinated. So, all six positions
are attached, to the ligand as well as the
other groups, coming from the protein chain.
So, we have the iron centre. So, it has only
option now, that it can settle between a oxidation
state of F e III and F e II, and at the
same time, will just talk about the corresponding
spin state, weather this iron center is in
the high spin state, or the low spin state,
and those spin states will be dictated by
the ethical binding donors; that means, the
donor atoms which are coming from the fifth
side, as well as from the sixth sides. So,
this thioether binding, the thioether sulphur
binding is a strong binding. So, that gives
us
only the option for low spin. So, we will
just settle between the iron three that is
the ferric iron, as well as the ferrous iron,
but
both of them are in low spin state. So, in
this particular case what we it have, it will
have one unpaired electron. So, it has one
paired electron. And at the same time it has
no unpaired electron.
And the porphyrin ring is given a charge of
l 2 minus from the deformation, because two
of the nitrogen atoms are barring the
hydrogen atoms. So, it has the l 2 minus in
this particular case, it has a formal charge
of 
plus one, and in this particular case the
formal charge would be zero. So, by settling
between these two, it will felicitate the
electron transfer. So it will be responsible
for,
until and unless some modification is taking
place, it will not go for a five coordinated
species, what we get for our myoglobin or
hemoglobin molecule; that means. One position
is vacant which is occupied by water molecule.
So, until and unless something
you do for these; that means, you take out
the thioether molecule or the hysterine residue,
you cannot transfer this particular
centre to a five coordinate at one. So, until
and unless you make it five coordinated, it
cannot bind to dioxygen molecule.
So, that will see afterwards for some other
type of molecules, that how you can make this
tetraperol nucleus to a five coordinated
one, which will be useful for binding the
dioxygen molecules. So, regarding the structure
of this porphyrin ring it is a basic
structure. I am just coming back again from
one structure to the another. So, if we just
simply able to draw in this form, the three
dimensional structure, bearing four petrol
unit which is a little bit different one,
what I have drawn right now. So you have these
nitrogen bearing rings here, then have other
two rings; that means, the petrol ring which
are bearing hydrogen. Similarly the other
one is also like this, they are connected.
So, what we have from just now is different.
So, it has a structure. So, two of these
terserinitrogen’s divide of hydrogen atoms
are pointing upward, and two N H groups are
pointing downwards, in a three
dimensional structure.
So, which is going to accept our iron centre,
which is supposed to be octahydral one in
the bear form also, when it is attached to
six water molecules. So, this is our OH2,
this is our iron. So, what will happen, so
this particular structure, which is known
as a
corresponding out of plane structure. So,
is also known as a deform structure, as a
seddling deformation, what is that, how it
is
known as this is then; that unprotonated nitrogen
atom, these are all unprotonated nitrogen
atoms. So, unprotonated nitrogen
atoms point up wards, and next the protonated
nitrogen atoms points downwards. So, the protonated
atoms point downwards. So,
what will happen next, that you bring this
iron above it.
So, these two nitrogens will be available
from the top only, so your iron will come
over here. So, we are bringing this on this.
So,
this is your iron, so it will form two bonds;
one with this nitrogen, and another with the
second nitrogen. So, it will have four
remaining water molecules, so this is a very
week interaction. So, iron centre is forming
by losing two water molecules. So, it will
immediately loose, two water molecules and
will sit above the particular porphyrin seddle
structure, and this particular structure
is also known and considered as this iron
is sitting atop complex, is known as sitting
atop complex. Then what will happen, this
next step is the important step; that means,
you can go for sequential depotonation of
the two nitrogen atoms; that means, this
hydrogen and this hydrogen one after another
will go. So is not a immediate one, but a
sequence, so sequential of the two petrol
nitrogen groups.
So, when they are depotonated, they will start
interacting with this iron centre, and ultimately
you get a metallated porphyrin, so
all four bonds are formed. So, it is not only
true for iron, but is also true for other
useful metal irons, which is giving rise to
some
important molecules like chlorophyll, or vitamin
B12 in case of corine molecule where we get
. So, now, the porphyrin is sitting
comfortably, within the cavity of the petrol
ring. So, within the ring, we get the corresponding
metallated porphyrin. So, this is the
way how these molecules are forming, the corresponding
complex with iron, with nickel, with cobalt,
and this will give rise to
your cytochrome molecule at the same time.
So, we have with this molecule 2 HCL ligands.
So, these axial ligands, play some important
roll that means form the position number 5
and 6, they basically control the
corresponding range of redox potentials. So,
the binding of these two groups; that means,
the binding form the fifth side, as well
as the sixth sides, which one is your histadin
18 and metheonin 80, this two you should remember
nicely. So, these two groups
basically control our ferrox potential, at
the same time, if we control the ionization
of the propionic acid side chain, because
you
still have two propionic acid side chain,
which have a typical values for the p k a’s.
So, in all these cases what we will see, in
all
these electron transfer chain, will just see
the detail of these; that means, whenever
there is transfer of electron from one side
to
the other; that means, in the biological system,
we have the membrane, and along these membrane
electron coming from one side
to the other, at the same time we will see
the proton is also going from one side to
the other.
So, proton is always playing some important
role to play, not only that in which direction
the electron is going, and how the
proton is of moving, in the opposite direction
or some time both of them are going together;
that means, the electron is moving, as
well as the proton is going for your deprotonation
and from the periphery of these porphyrin
ring. You have the two propionic
acid side chain, and those two propionic acid
side chains will go for the different deprotonation.
So, you have the microcyclic
ring, and here you have this chain, and here
you have the chain for the propionic acid
groups. So, this particular ligand, which
is
functioning as l 2 minus to the deprotonation
of the nitrogen atoms only. So, we are not
considering the corresponding protonation
as well as the deprotonation of the propionic
acid side chain, by depending upon the availablethe
p H value of the system; that
means, in which particular part of the cell,
or in the biological system where you have
a typical p H.
So this particular p H will control this corresponding
protonation level, of these protonic acid
side chain, so this is nothing but
your porphyrin. So, that particular protonation
will control our different e zero values.
So, this particular proton will also behaving
as a valve for your electron transfer, because
sometimes if it is a metal centre electron
transfer ,will see that iron 3 plus is
reducing to iron 2 plus, and we can have a
typical e zero value, and in the biological
system, if we are able to determine, the
corresponding p H, we all the time if it is
dependent on the corresponding proton gradient
or the p H. So, the e zero value we
have to report, against the different p H
values. So, this p H value you should also
know the corresponding buffered medium. So,
if you have a acidic buffered medium and if
you can have a basic buffered medium, you
will get two different e zero values. So,
basically the p H, the proton in the system
will control the corresponding e zero value,
whether you that cytochrome will accept
the electron, or whether that cytochrome will
donate the electron, within the environment
you can have the corresponding
protein chain and all other thing as well
as you have the corresponding proton gradient,
that will control the different e zero
values.
Thank you.
