Hello, welcome to the course Biochemistry
1 conducted by me Dr. S Dasgupta, Department
of chemistry Indian institute of technology
Kharagpur.
In this course we will be studying certain
aspects of Biochemistry starting from structures
and functions of Biomolecules right on to
Bioenergetics and Metabolism.
The topics we will be covering are structures
and functions of Biological molecules.
In that we will be considering Amino acids
and Proteins, Enzymes.
Under the Enzymes we will be considering the
mechanisms of specific enzymes move to Vitamins
and Coenzymes, Carbohydrates and Lipids, Nucleic
acids and their components.
The entire range of topics of this course
will be covered in their detail as is relevant
to this course.
Also we will be considering the Principles
of Bioenergetics with special reference to
carbohydrate metabolism.
The books we will be covering are common Biochemistry
books such as Stryer, Lehninger, Voet & Voet.
When we consider “The Central Dogma of Biology”
the first thing that comes to mind is DNA,
the DNA is the storage medium.
The Central Dogma of Biology goes like this
DNA ? RNA ? Protein.
We have a text that is comprised of DNA which
is the four basis of DNA that is the storage
medium and this is transcripted to RNA which
is the transmission medium that also is comprised
of four basis one of them being a bit different.
The RNA is then translated to the Protein.
The alphabet of DNA, RNA and Protein is slightly
different.
What is this alphabet?
In DNA we have four letters to the alphabet
the four letters are as you can here A, G,
T and C. These are the four letters that comprise
the alphabet of DNA.
If you look at the corresponding alphabet
of RNA you will see that we have U, C, A and
G.
When we go on to study the structure and contents
of Nucleic acids the structures of each of
this basis will be much clear but we have
to know that DNA and RNA are comprised of
these letters which actually represent nitrogenous
basis.
The Protein alphabet is a bit different the
Protein alphabet is some times represented
as a 3-letter code which we will see in a
moment or by the 1-letter code which is another
representation of the very same 3-letter code.
The Protein alphabet is comprised of twenty
unique letters that tell us what the Protein
sequence is.
We will understand what an Amino acid sequence
is once we get into the details of what is
a peptide bond and what is an Amino acid.
The first thing that we know or we try to
understand here is the carbon atom.
The Proteins are actually made of the Amino
acids that are linked by peptide bonds.
We will also see how a peptide bond is actually
formed and how these letters were linked together
to form like a sentence.
Each amino acid consists of: a central carbon
atom Ca so we have the central carbon atom
that is marked as Ca and we have an amino
group NH2 group, and we have the carboxylic
acid group which is -COOH and we also have
what is called an R group.
This R group is the side chain of the amino
acid.
And we also have the hydrogen atom.
This part is common to all Amino acids because
it has an amino group, it has an acid group,
it also has an H a hydrogen attached to it.
So we see this central carbon atom is actually
a chiral carbon which means it is asymmetric
which again means that there are four different
groups attached to this central carbon atom.
And since all amino acids have a common set
of groups here in the amino group, the hydrogen
atom and the carboxylic acid group.
The side chain differs from one amino acid
to another amino acid which can be different
atoms, different groups of atoms and this
is what actually distinguishes the various
amino acids.
Now we are going to consider the types of
R groups we can actually have.
If we look at the different forms of amino
acids that could be incorporated into proteins
as we mentioned earlier we have an amino group,
an carboxyl group, an hydrogen atom and we
also have an R group attached to it.
Now because of its chirality it can have an
L -form or a D –form.
Usually L -amino acids are incorporated into
proteins.
Now you understand that these side chains
the R group can differ in its size, it can
differ in its shape, it can differ in its
polarity.
There are twenty common amino acids which
have distinctive R groups with distinct properties
of size, shape and its polarity.
We will consider the amino acid side chains
by group in each case and you have to remember
the 3-letter code of the amino acid along
with their 1-letter code as well and obviously
you have to remember what the side chain comprises.
We have listed here is Glycine and Proline
which are unique amino acids.
The Glycine is the simplest amino acid because
the R group is just a hydrogen atom.
This hydrogen atom makes the central carbon
atom of Glycine symmetric because it does
not have four different groups attached to
it.
It was attached with two hydrogen atoms which
do not make it chiral anymore and this is
the only such amino acid.
So, if we look at the Glycine the side chain
the R group is attached to central carbon
atom and we have an amino group and also a
carboxylic acid group attached to it.
We have all the amino acids are in the form
of NH3+ and a COO- because at physiological
pH 
the –OH group looses its hydrogen atom due
to pk value of the carboxylic acid group and
this amino group is protonated which means
that it has an additional hydrogen atom making
this nitrogen positively charged and this
is called the zwitterion form of the amino
acid and it is 
represented in this fashion because we would
like to represent the amino acids as what
they would be at physiological pH.
The next unique amino acid is Proline.
The Proline does not have a distinct R group
attached to it but the R group is actually
linked up to the amino group here.
So the side chain -CH2 -CH2 -CH2 is actually
linked to the NH+ in this case.
So the a- carbon have attached with a hydrogen
atom, with a carboxylic acid.
But the Proline is being as an imino acid
instead of being an amino acid because it
has an imine group instead of an amine group.
So we have an imino acid where the side chain
bends on to itself to form Proline.
So these are the two amino acids that are
unique in their features.
The Glycine is being just because it has an
hydrogen atom as its side chain and it is
achiral.
And the Proline is being as an imino acid
because the side chain bends back upon itself.When
we represent the amino acids we represent
them in Zwitterionic form which is NH3+ and
COO- . Because this is how they would remain
at a physiological pH in normal solution.
The next group of Amino acids is hydrophobic
amino acids.
The Hydrophobic amino acids are comprised
of mostly of carbon atoms and hydrogen atoms
in their side chains.
So they would tend to be away from the solvent.
Usually the solvent being water or water based.
They would be away from water, not liking
to be in water so they would be Hydrophobic.
Here the simplest side chain having amino
acid is Alanine.
In which the 3-letter code is Ala and the
1-letter code is A. The side chain is a methyl
group so this is what we would say the R group.
Here again you recognize the Zwitterionic
representation of amino acid.
Then we come to Valine.
The Valine is a ß-branched amino acid.
Its side chain is -CH(CH3)2.
The next one we have is Leucine in which the
R-group is -CH2 -CH(CH3)2..So it is branched
at the ?-atom.
The way these are represented is that if this
is the Ca the next atom is the Cß beta which
is connected to 2 C?
atoms which would be a unique representation
of the amino acid Valine.If we look at Leucine
we would again have a unique representation.
We will consider this as Ca, the next one
which is attached to this is Cß and then
C?.
It is attached to the 2 Cd atoms in which
one is represented as Cd1 and the other as
Cd2.
The Alanine side chain has only a Cß-carbon.
So this code actually be represented very
clearly in a unique manner where each amino
acid has this zwitterionic part being common.
The chain could be represented by the types
of atoms that are attached to the Ca.
If you look at the Isoleucine we have the
side chain –CH(CH3) –CH2 –CH3.
So we have a Cß atom attached by one methyl
group and one ethyl group.
All these side chains are comprised of C and
H which makes them Hydrophobic in nature.
In the same way the Methionine can fall into
this category is well.
But it has a Sulphur atom and a methyl group
attached to the Sulphur atom in its side chain.
So we have a Ca attached with Cß which is
C?.
And this C? is attached to the Sulphur atom
and then we have a methyl group attached to
the Sulphur.
The Methionine along with another amino acid
Cysteine is the Sulphur containing amino acids.
They could be grouped together in a group
of their own or they could be considered in
this group as well.The next group that we
will be considering is the Polar amino acids.
The Polar Amino acids have an oxygen atom
or a nitrogen atom in their side chain.
And by virtue of having the hetero atoms like
the oxygen or the nitrogen in the side chain
is they can participate in polar interactions
not only among themselves but also with solvent
molecules.
So they can participate in Hydrogen bonding
which is extremely important in non-covalent
interactions in Proteins which holds a Protein
fold it together in the protein chain the
amino acid chain.
But the Polar amino acids are likely to interact
with the solvent.
In this interaction they can allow the oxygen
and nitrogen atoms to interact with the solvent
molecules or within themselves to form a network
and remain in solvent.
In contrast the hydrophobic amino acids are
unlikely to be on the surface of the protein.
So when we have an globally structure we will
see that there are certain side chains are
preferred to be on the surface of the protein
and there are certain side chains that are
preferred to be away from the solvent which
we have seen earlier would be the Hydrophobic
in nature.
Now, if you to look at the side chains that
are comprised this polar group of amino acids.
Each of these have an oxygen or nitrogen attached
to it.
We have of course the common part of amino
acid in the Asparagine side chain and in the
glutamine side.
These two amino acids have amide group in
its side chain.
The amide groups are -C(O)NH2 groups.
So this -CH2-C(O) -NH2 group comprises the
amide of Asparagine.
This -CH2 -CH2 -C(O)-NH2 group comprises the
amide of Glutamine.
Here the only difference is the Glutamine
chain is one carbon longer than the Asparagine
chain.
So here we have a -CH2 group that is the ß-carbon
attached to the a-carbon followed by a ?-carbon
that has attached with an oxygen atom and
then -NH2 group.
So in Aspargine the amide group has a single
ß-carbon attached to the a-carbon.
In Glutamine we have two -CH2 moieties in
the side chain.
We have Ca, Cß, C? and Cd carbons.
And this Cd is attached with oxygen by a double
bond and with a -NH¬2 group.
So in Aspargine and similarly in Glutamine
the oxygen, nitrogen can participate in Hydrogen
bonding which means if we have a specific
donor or an acceptor then this could participate
in Hydrogen bonding not only with other amino
acids but also with the solvent.
In this group the next amino acid is Serine.
The Serine is a small amino acid but a polar
amino acid.
The group it has is -CH2OH and this -OH can
participate in the Hydrogen bonding.
In this series Threonine is the next amino
acid.
It has a -CH3 group and a –OH group attached
to the ß-carbon so again it differs from
Serine.
The next amino acid in this group is Cysteine.
The Cysteine is another type of the amino
acid which has a Sulphur atom same as in Methionine
which also has a Sulphur atom but the Sulphur
was attached by a methyl group.
Here we have a hydrogen atom making this ethyl
so we have -CH2SH.The Histidine is a very
important amino acid.
Enzymes and the Enzyme mechanisms will be
covered in detail about the Histidine because
of its specific polarity or specific properties
of this side chain that is an amidazole group.
So again Histidine have a common amino acid
part.
In the side chain of Histidine have two nitrogen
atoms which are in part of the amidazole protein.
So the side chains of all these polar group
of amino acids have contained a hetero atom.
We will be considering the next group of side
chains are Acidic Amino Acids.
Earlier we looked at Asparagine and Glutamine.
The Aspargine has the -C(O)NH2group.
We know that an amide comes from a carboxylic
acid.
So the Asparagine comes from a specific carboxylic
acid.
Similarly the Glutamine also comes from a
carboxylic acid.
So we group them into Acidic Amino Acids and
we call these specific acids as the Aspartic
acid which gives rise to a Asparagine and
Glutamic acid which gives rise to Glutamine.
Now we have here is a -COO- group.
This -COO- group is apart from the actual
carboxylic acid that is common to all amino
acids.
This is part of the R group the side chain.
So the side chain in Aspartic acid also contains
a carboxylic acid group.
Similarly the side chain in Glutamic acid
also has the carboxylic acid group but it
has an additional -CH2 just as like in Glutamine.
Here in addition we have a pKa value.
If the pKa value is less than pH in a solution
then carboxylic acid is going to loose its
proton similarly the carboxylic acid looses
its proton but this amino group has not.
Because the pKa value of this amino group
is actually higher than physiological pH which
is why it has still kept its proton attached
to it.
But if we consider the physiological pH to
be 7.4 it means the pKa of this group is greater
than 7.4 and we will see how it is actually
something close to 9 or between 9 and10.
So if we have the pKa >7.4 this is going to
remain protonated but these carboxylic acid
cannot remain protonated.
So these are comprised as Acidic Amino Acids.
If there are Acidic Amino Acids it means that
there are also be Basic amino acids.
These are Lysine and Arginine.
Now we will look at the side chain groups
of the Lysine and the Arginine.
This is the long side chain of Lysine and
this is the side chain of Asparagine.
Now each of these two amino acids has different
pKa values.
The amino groups are still protonated because
of the pKa values are greater than the physiological.
So we have protonated nitrogens because the
physiological pH is 7.4.
And it did not reach the pKa value where this
is going to loose its proton.
So, here we have an additional amino group
apart from the common part of the amino group
because it is a Basic amino acid.
We have a guanidinium group in Arginine which
is part of the side chain and it has nitrogen
here, nitrogen here and nitrogen here.
So this is Lysine and this is Arginine.
Especially these are the residues preferred
to be on the surface of the protein especially
because of their properties.
So, if we look at the different structures
of the amino acids in which we have considered
specific groupings.
The different groupings are the GLYCINE and
the PROLINE which forms a group by itself
because of the uniqueness in their properties
and we have the other group the POLAR AMINO
ACIDS, we have HYDROPHOBIC AMINO ACIDS, we
have ACIDIC AMINO ACIDS 
and we have BASIC AMINO ACIDS.
There is another group of amino acids the
AROMATIC AMINO ACIDS.
The Aromatic amino acids are unique and Aromatic
in nature, under these we have three amino
acids namely Phenylalanine, Tyrosine and Tryptophan.
Here we have Phenylalanine.
As we have seen earlier the Alanine was just
a methyl group attached to the a-carbon.
But in this case one -H has been replaced
by a phenyl group so its name is Phenylalanine.
Of course it also has the common part of the
amino acid.
The 3-letter code for Phenylalanine is Phe
and the 1-letter code is F.
So we will get Phenylalanine by replacing
one -H with phenyl group in Alanine side chain.
So this is Aromatic in nature.
Then we have Tyrosine which is similar to
Phenylalanine but the only difference in the
side chain one hydrogen is replaced by an
–OH group.
So the Tyrosine can actually also be involved
in hydrogen bonding.
In the grouping of amino acids this could
also be put in a Polar group but it is already
grouped under the Aromatic amino acids because
of the presence of phenyl ring.
So the Tyrosine have a -CH2 and a phenyl and
an -OH attached to this phenyl ring.
In this group the other amino acid is the
Tryptophan.
It has an Indole ring attached to this –CH2.
This is very bulky amino acid as you can see
by the size of it and it is quite rare in
Proteins.
So it is not present in very large extent
in many of the Proteins.
The unique properties of these Aromatic amino
acids are makes the Protein 
useful in an analytical way.
All the Aromatic amino acids which are Phenylalanine,
Tyrosine and Tryptophan are absorbs the Ultra
violet (UV) light.
So their presence in Proteins can actually
be neutralized in this fashion.
This means they absorb UV light in the range
of 280nm.
Even though they have different ?max values
but we usually look at 280nm to identify a
Protein.
If a solution 
has a certain amount of Protein in it so we
can determine the amount of Protein present
in the solution by a consideration of the
number of Phenylalanine, Tyrosine and Tryptophan
that are present in the Protein chain.
So, if we monitor or if we find out the Absorbance
at 280nm we know that the extension coefficient
of the protein and we know the length of the
cell and we also know the absorbance at 280nm
which is also represented as A280 then we
can determine the concentration of the protein.
So the presence of these Aromatic amino acids
can help in determining whether the solution
is actually contained the protein or not.
We can also find out the content of the concentration
of the protein in solution by virtue of having
Phenylalanine, Tyrosine and Tryptophan.
In which the Ttryptophan has the highest extension
coefficient which means if you have a large
number of Tryptophan amino acids in the protein
you are going to have a larger absorbance
at 280nm.
But the presence of the Aromatic amino acids
themselves will give an absorbance at 280nm
which is how proteins are monitored in Biochemistry
laboratories.
The next thing we are going to look at is
a representation.
As we have seen already we have a carboxylic
acid group, we have an amino group, and we
have a hydrogen atom which is common to all
amino acids and we have a side chain, R. Here
the side chain is an amide group.
Asparagine and Glutamine are the amide group
having amino acids.
So the Glutamine side chain had two –CH2
groups.
The 2 –CH2 groups attached here.
This is a stick representation where the asymmetric
carbon is in green, the other carbon atoms
are in grey, the nitrogen atoms are in blue
and the oxygen atoms are in red.
If we look at the linking of these amino acids,
we know these amino acids are the building
blocks in the formation of proteins.
These building blocks have to be linked together
to form a protein.
They are linked together by a peptide bond.
Now the representation here is not zwitterionic
representation because the proton of the carboxylic
group is attached to it and this is the NH2
group.
In actual form it would remain as -NH3+ and
-COO-.
Here we have two R groups and the first amino
acid has an amino terminal, the other has
a carboxylic terminal.
So this is a di peptide because these two
amino acids were linked by a peptide bond.
This peptide linkage has a carbon with doubly
bonded oxygen and a _NH group.
But as we have here is the two R groups that
in the first amino acid which is on the left
hand side has an amino terminal.
so this is a di-peptide because the two amino
acids linked were by a peptide bond.
The original amino acids were missing an -OH
from the carboxylic acid side and missing
-H from the amino side to form a peptide bond.
These were makes an H2O molecule.
So the linking to two amino acids by the elimination
of H2O can form a peptide bond.
We will look into the features of the peptide
bond once we considered the protein structure
in general and the amino acid sequence.
But when these amino acids are linked together
on the left hand side you always have the
N terminus and on the right hand side you
always have the C terminus because this is
the way the proteins are formed where this
is the way they are synthesized.
So we have an amino terminal and we have a
carboxylic acid terminal.
The first amino acid is always has the NH3+
group attached to it and the last amino has
the -COO- attached to it acid in a protein
sequence or in a protein chain.
So this is a di peptide linked by a peptide
bond.
There are certain features of the peptide
bond unique to protein structure.
Here we have an amino acid the Glycine which
is having a Zwitterionic representation.
The Glycine is a unique amino acid where the
R group is H where this R is the side chain
representation of the amino acid.
Here now the R group is CH3 in case of the
Alanine and the R group is –CH2SH for Cysteine.
For Glycine we actually cannot distinguish
which is the R group because the hydrogen
is present and the hydrogen is also the side
chain.
So we have an -NH3+ and a -COO- and by eliminating
water into forming a peptide -C(O)-NH-.
So we have two peptide bonds a -C(O)-NH- and
a -C(O)-NH-.
So we have Gly -Ala -Cys in the formation
of a tri peptide.
And this can continue to form other peptide
linkages.
So we have a Ca and we have –NH3+ group
and 
we have -COO- group, we have H atom and an
R1 group is attached to this in the basic
structure of the amino acid.
If we look at other amino acid you would have
another –NH3+ group, we have -COO- and we
have H and we have R2 group.
So now when we combine these two amino acids
to form a di peptide we would have linked
these by a peptide bond.
So we have a -C(O) connected to -NH which
is coming from the second amino acid, we have
an a-carbon, we have R1and R2, the two hydrogen
atoms and the COO- group and –NH3+ group
in this di peptide.
So this particular linkage is known as the
peptide linkage.
Now we have linked the R1 and the R2.
In a representation of a protein it is not
very convenient to keep on writing all the
atoms together.
We already knew that the amino acids are the
building blocks in the protein sequence in
the primary amino acid sequence which are
linked together by the peptide bonds.
Now since they are just linked by the peptide
bonds.
Then it is not necessary to write the common
part of all the amino acids because these
are certain features that we already know.
We know that the first amino acid is going
to be linked with the -NH3+ terminal and we
know that the last one is going to be linked
with the -COO-.
So it is sufficient to write instead of writing
-NH3+ and -COO- in each case in a laboratory
fashion.
When we write a protein sequence all the information
we actually need is R1 and R2.
.Because we know each amino acid looks the
same but it differs only in R group.
So if we just know the R1 and R2 we need to
know about how they are linked together in
the protein sequence.
Suppose in this protein sequence if this is
one amino acid and this is the other amino
acid.
Then this first amino acid has to have the
–NH3+ attached to it and therefore3, 4 so
on and say to 120 will have the -COO– attached
to it.
And also we know that these linkages are nothing
but peptide bonds.
So here we need to know what R1 is, what R2
is, what R3 is and what R4 is so on up to
R120 in this sequence.
Here we just write either the 3-letter code
or the 1-letter code.
In the 3-letter code, if this first one were
a Glycine then we would write as Gly and it
is linked with for say Alanine which is represented
as Ala linked with acidic amino acid Aspartic
acid linked with a basic amino acid Lysine
and so on and so fourth the sequence represented
as Gly -Ala -Asp -Lys -•••••• because
when we have the Glycine and the Alanine and
the Aspartic acid so we know what are the
rest of the atoms are because we know the
side chain of the Glycine and we know the
side chain of the Alanine and so on and so
fourth.
If we write this in a one letter code it would
be G -A -D -K so just wrote as GADK you could
write those structure of this tetra peptide.
Similarly when we consider a whole protein
chain in this case say just one hundred and
twenty amino acids so the difference is in
the properties of the amino acids side chains.
Here the first property is the Size and shape
of the amino acid.
It is extremely important in its accommodation
in the protein.
The next property is the Charge on the protein
whether it is acidic or it is basic.
Next we look at the polarity whether it can
be involved in hydrogen bonding or is it a
polar amino acid.
Then the Hydrophobicity, where this amino
acid is likely to be located whether it is
going to be located in the centre of the protein
because its likes to be away from the solvent
or whether it is going to be likely to be
on the surface of the protein.
But we know that any hydrophobic amino acid
would prefer to be in the core of the protein.
The next one is the Aromaticity, the aromatic
amino acids that we are considered Phenylalanine,
Tyrosine and Tryptophan are important in imparting
UV properties to amino acids because these
are the one set that absorb UV light.
The proteins can be detected in solution due
to the presence of the Aromatic amino acid
which will absorb the UV light.
And from the Beer Lambert’s law we can find
out the concentration of the proteins.
Now the confirmation, as we have already seen
this is usually determined by the side chain.
We will see the most of the side chains are
linked by the single bonds.
Also we will see how rotation about the side
chains can actually bring about conformational
changes to the amino acid orientations in
the proteins.
And this change in confirmation or the change
in dihedral angles will allow us to look at
different properties of amino acids in the
way they interact with the other amino acids.
We also look at the propensity to adopt a
particular conformation.
What does it mean?
It means that if a protein were to have an
amino acid that would likely form a helix
or be part of a helix.
We will see whether it is likely to be in
a helix or it is likely to be in a sheet.
So, the summary of today’s lecture is the
different types of amino acids, the different
groupings of amino acids and the important
properties of the side chains of the amino
acids.
We were considered the central carbon atom
is the asymmetric carbon atom which is also
known as the a-carbon atom has linked to four
different groups.
These are hydrogen atom and amino group and
carboxylic acid group and a side chain that
is represented as R. We have twenty different
common amino acids each having these various
R groups.
The twenty amino acids have twenty different
R groups that differed largely in their properties.
We have different types of amino acids which
are grouped into the type of R group the type
of side chain that they have attached to them.
We have unique amino acids Glycine and Proline.
we have Hydrophobic amino acids and we have
Polar amino acids, we have Acidic and Basic
amino acids and we have Aromatic amino acids.
Methionine and Cysteine are Sulpher containing
amino acids and there are other sets we have
here is the hetero atoms oxygen atoms and
nitrogen atoms in them and the side chains
comprised entirely of carbon and hydrogen
making them hydrophobic in nature.
And lastly we look at overall properties that
we can consider together are the Size and
shape, the Charge, the Polarity, the Hydrophobicity,
the Aromaticity.
All of these will actually determines the
property of the protein in general.
Because we know that these amino acids are
linked by peptide bonds.
These linkages of the peptide bonds bringing
different types of amino acids together to
form a protein sequence.
We have seen the peptide bonds and we saw
how the amino acids were linked together by
the peptide bond and how we can actually represent
the protein sequence by just writing either
the 3-letter code one after the other or the1-letter
code one after the other.
Because we know that the first amino acid
will have N terminus and the last amino acid
will have C terminus which means that first
amino acid is going to have the -NH3+ attached
to it and the last amino acid is going to
have the -COO- attached to it to making up
the protein chain.
We will learn in the later classes how the
protein actually folds and how the hydrophobic
amino acids tend to remain in the centre of
the protein, thank you.
