Good morning students. In the earlier classes we have all ready learned the glycolytic process,
TCA cycle, electron transport chain and oxidative phosphorylation and which completes the cellular
respiratory process. Now, during that process we have seen that how glucose is oxidized
and this flow of this pathway starts and it ends with this pyruvate and then it enters
to the TCA cycle and ultimately it ends with the oxidative phosphorylation process.
During this process we have also seen that how ATP is being generated in that process.
Now, we have also seen that NADH is playing a significant role in this glycolytic to oxidative
phosphorylation process. Today the topic of our discussion is pentose phosphate pathway
which is little bit different from that of the earlier metabolic pathways what we have
discussed. Now, in the earlier processes I have all ready
told that it is the respiratory process and this is the catabolic process. But, in this
today’s topic this pentose phosphate pathway, what we will be discussing here will have
some product which is different from the generation of NADH. Now, the product is the NADPH. Now,
we must know the difference between NADH and NADPH. Now, if we see this difference between
NADH and NADPH we can find that, when NADH is getting oxidized in these earlier processes
that cellular respiratory process ATP is generated. That means, the cell is getting ATP when NADH
is getting oxidized. But, the today’s concern is with NADPH which is acting as the electron
donor and it is the product which is the which is reductive biosynthetic pathway. And it
is helping in very many cellular activities going on inside the cell.
And today, I will be starting with pentose phosphate pathway and then I will be coming
to the glycogenesis and glycogenolysis. Now, let let us start with the pentose phosphate
pathway. Pentose phosphate pathway is otherwise known as phosphogluconate pathway or hexoes
monophosphate shunt. In this process, in this biosynthetic pathway, it generates NADPH and
pentose sugar that is five carbon sugar. If we see the entire pathway we can divide the
entire pathway into two distinct phases; the first is the oxidative phase in which, NADPH
is generated, in the second phase the non-oxidative synthesis of five carbon sugars are there.
This is the pathway which is alternative to the glycolytic pathway. While it does involve
oxidation of glucose, its primary role is anabolic then the catabolic process. In most
of the organisms this pathway is taking place in the cytoplasmic fluid of the cell. But,
in plant this particular step is taking place in plastid.
Now, as I have all ready told you that NADPH generation is there in this particular pathway,
what is the important of NADPH? Now, if we see the function of NADPH then, we can find
that this NADPH is acting as the reducing power carrier. That means during this metabolic
process during when the activities several activities are simultaneously going on within
the cell then, some molecules that we as a result of oxidative oxidation free radical
generation is taking place. Now, when free radicals are formed these free radicals are
harmful to the cell. What these reducing power carriers are doing? They are acting as the
scavenger of those free radicals which are produced during this reaction. NADPH is acting
as one of such antioxidant and it is playing a important role in cellular ant oxidation
process. I have also told you that another bi product is the five carbon sugar that is
the ribose sugar. And in our earlier classes we have all ready learned that, five carbon
sugars are very important as for as this nucleic acid is concerned. And if we see the structure
of nucleotide then we can find that in the nucleotide code structure this five carbon
sugar moieties are there along with that nitrogen group and as along and another phosphate group
is attached to that. This is the nucleotide and this sugar is the ribose sugar. In case
of RNA it is the ribose sugar and in case of DNA it is deoxyribose sugar.
So, this ribose sugar is playing a significant role in other biochemical reactions which
are going on inside the cell. So, if we see the pentose phosphate pathway it starts with
glucose and when glucose is converted to glucose 6-phosphate. This glucose 6-phosphate may
get diverted to different pathways. That means in a cell simultaneously different activities
are going on and this glucose 6-phosphate may take part, may get converted to fructose
6-phosphate and it can enter to this glycolytic process. When glucose 6-phosphate is converted
to glucose one phosphate, it enters to the synthesis of glycogen from glucose. Glucose
6-phosphate when it enters to and produce the product like 6-phosphogluconate, it enters
to this pentose phosphate pathway. And today, we will learn this particular pathway where
glucose 6-phosphate is producing the pentose sugar.
The As I have told you, that when in a cell oxidation reactions are going on simultaneously
I am telling that free radical generations are taking place and there this reduced glutothiones
which are there it is acting as antioxidant. Then this NADPH has got high demand for the
generation of super oxide that is neutrophils in the cell. It also helps in detoxification.
If we see the different biosynthetic pathway then we can find that, fatty acid biosynthesis
which takes place in liver in adipose tissues and in memory gland if there NADPH has got
a significant role. It has got also, it is playing this NADPH is playing also a significant
role in cholesterol biosynthetic pathway which takes place in liver and steroid hormone synthesis
which takes place within the cell that is in adrenal ovaries and testes. This NADPH
is playing a significant role and that is the reason why today’s pathway is so important
to learn.
As I have told earlier this glucose may enter to different pathways for doing different
metabolic activities in the cell. When glucose is glucose concentration is more in the cell
it can be used it can be stored in the form of glycogene which is stored in the liver.
Glucose can also oxidize and entered to this pentose phosphate pathway. Glucose can also
oxidize to form this pyruvate. And today’s lecture is how glucose is converted to five
carbon pentose.
Coming to the first step of pentose phosphate pathway, now as we have all ready seen that
glucose is converted to glucose 6-phosphate. So, glucose 6-phosphate when it under go some
reaction like glucose 6-phosphate in the presence of the enzyme glucose 6-phosphate dehydrogenase,
it produces 6-phosphoglucono delta lactones. Now, here one molecule of NADPH is produced
in this reaction. This is, this particular enzyme glucose 6-phosphate dehydrogenase is
playing a significant role which controls this particular pathway.
When 6-phosphoglucono d lactone is produced, it is getting converted to 6-phosphoglconate
in the presence of one molecule of water and the enzyme lactonase which hydrolyses 6-phosphoglucono
d lactone to 6-phosphogluconate.
When 6-phosphogluconate undergoes oxidative reaction it produces ribulose 5-phosphate.
Here another molecule of NADPH NADP is required to convert to NADPH in the presence of 6-phosphogluconate
dehydrogenase enzyme. Now here, dehydrogenation reactions are going
on, simultaneously carboxylation reaction is also going on. Here see 6 carbon molecule
is getting converted to 5 carbon molecule and a one molecule of carbon dioxide is being
released in this particular step.
When ribulose 5-phosphate is produced, ribulose 5-phosphate in the presence of isomerase enzyme
that is phosphopentose isomerase this ketopentose sugar is converted to aldopentose sugar. That
means ketose sugar is converted to aldehydic sugar. That means ribose 5-phosphate and here
this ribose 5-phosphate is formed.
This ribose 5-phosphate is formed in this oxidative phase of this pathway is incorporate
incorporated into various product products. But, any extra pentose phosphate is recycled
back to glucose 6-phosphate. This is particularly important in those tissues such as erythrocyte
that requires NADPH produced by this pathway. But, have a lesser requirement of a ribose
5-phosphate. The recycler process is essentially a process of cutting and pasting carbohydrate
molecules with different number of carbon sugars. Obviously 6 pentoses can be combined
to yield 5 hexoses. Each of the reactions is reversible in nature.
Now, when we are going to this non oxidative pathway then step one is this a ribulose 5-phosphate
which is there once again in the presence of this enzyme epimerase. That is a ribulose
5-phosphate epimerase enzyme can convert this ribulose 5-phosphate to xylulose 5-phosphate.
Now, this is that epimere epimera of these two sugars ribulose and xylulose. Both are
pentose sugar.
Now here when xylulose 5-phosphate and ribose 5-phosphate, this see here it is the ketopentose
and here it is the aldopentose.
Now when 5 carbon plus 5 carbon, now 5 plus 5 ten carbon under goes reaction that is in
the presence of transketolase enzyme; you see 5 plus 5 this 10 carbon sugar when under
goes this reaction it produce 1 3 carbon sugar and another 7 carbon sugar. So, 5 plus 5 is
getting converted to 3 plus 7, 10. So see the carbon balance here. In the presence
of the enzyme that is the transketolase so this enzyme what it does? Transketolase is
then moved to carbon unit of xylulose 5-phosphate, a ketose to ribose 5-phosphate and then it
becomes so when 2 carbon is coming from this sugar to this. Then it transforms its orientation
from 5 sugar to 7 carbon sugar. And that is the sedoheptulose sevenm phosphate and this
is and one glyceraldehyde three phosphate that is the three carbon sugar. Now, in the
third step what is happening? This seven carbon sugar which is there and this three carbon
sugar which is produced in this step undergo transaldolace reaction. Now when see once
again, this is seven carbon, this is three carbon and here this ten carbon. Once again
and it under goes reaction and it produce one C 4 sugar, another C 6 sugar. So, 6 plus
4 10, 7 plus 3 10. So, here these transaldolace reactions are going on and it produces one
4 carbon sugar and another 6 carbon sugar.
Now, here you see when this reaction is going on this transaldolace cut a three carbon fragment
from sedoheptulose seven phosphate and link it to the glyceraldehyde three phosphate yielding
one fructose 6-phosphate and one 4 carbon erythrose 4-phosphate. You see this is the
ketos sugar, this is a aldose sugar. Here is this aldose sugar and it is the ketos sugar.
Now, this fructose 6-phosphate can enter glycolytic process and this reaction is similar to that
catalysis the aldolysis in glycolytic pathway. In the next step this xylose 5-phosphate and
erythrose 4-phosphate.
So we have seen by xylose in a step xylose 5-phosphate and erythrose four phosphate.
This 5 plus 4 9 carbon sugar undergoes transketolace reaction in a presence of the enzyme transketolace.
It undergoes it its biotransformation and it produce that C 6 and C 3 that 1 3 carbon
sugar and another 6 carbon sugar.
Now here you see the transketolace then moves that 2 carbon unit of xylulose four phosphate
to erythrose 4-phosphate forming fructose 6-phosphate and glyceraldehyde three phosphate.
Both these three carbon and 6 carbon sugars we have all ready learned are the intermediate
of glycolytic pathway. A second round of the cycle would produce two molecules of glyceraldehyde
three phosphate which can be converted to fructose 1 6 bisphosphate by aldolace enzyme.
Some of the enter reactions then we can divide the entire p p p pathway into two distinct
phases; once is the oxidative phase, another is the non oxidative phase. In case of oxidative
phase, we have seen that glucose 6-phosphate is producing two molecules of NADPH, one molecule
of carbon dioxide and 6 carbon sugar is converted to 5 carbon sugar. This 5 carbon sugar under
goes this isomerize isomerization reaction and ribulose becomes ribose this aldose aldose
sugar. And here with this 5 carbon 2 5 carbon sugar one aldose and ketose origin, they undergo
different types of non oxidative reactions and we have see that there is a production
of C 3 C 4 C 5 C 6 C 7 etc sugar. And these are the intermediate and ultimately we have
seen that fructose 6-phosphate which is produced can once again rebound back to glucose 6-phosphate
or fructose 6-phosphate can enter to the glycolytic pathway.
So if we sum up this what are the outcome of this p p p pathway, that is pentose phosphate
pathway. The generation of reducing equivalents in the form of NADPH used in reductive biosynthesis
reaction within the cell, production of ribose 5-phosphate used in the synthesis of nucleotide
and nucleic acid, production of erythrose four phosphate this 4 carbon sugar which is
there is acting as the for the synthesis of aromatic amino acids. So, we can see that
each of the intermediates which are produced in this pathway is playing a significant role
in the living system.
Now, if we see the role of NADPH in a red blood cell; in red blood cells the major role
of NADPH is to reduce the disulfide form of glutathione to the sulfhydryl form. The reduced
glutathione is pertinent for maintaining the normal structure of a red blood cell for keeping
hemoglobin in the ferrous state. And red blood cells used this pathway to produce needed
NADPH to maintain the reduced iron and to maintain the concentration of reduced glutathione
and this is the major role of NADPH in the in blood.
Now, overall reaction if we see glucose 6-phosphate plus two molecules of NADP and one molecule
of H 2O is releasing a ribulose 5-phosphate plus 2 NADPH plus 2 hydrogen and one molecule
of carbon dioxide. In non oxidative phase, three ribulose 5-phosphate is giving one ribose
5-phosphate, two xylulose 5-phosphate which under goes further reaction to yield two molecules
of fructose 6-phosphate and glycerdehyde three phosphate which are the end product of this
p p p pathway.
Now, if we see the regulation of this p p p pathway, we can find that the entry of glucose
6-phosphate into pentose phosphate pathway is controlled by the cellular concentration
of NADPH. NAPDH is the strong inhibitor of glucose 6-phosphate dehydrogenase. That means,
in this way the reaction is being controlled by the this NADPH and 6 phospo dehydrogenate.
As NADPH is used in various pathway inhibition is relieved and the enzyme is accelerated
to produce more and more NADPH. The synthesis of glucose 6-phosphate dehydrogenase
is induced by the increased insulin or glucagon ratio after the high carbohydrate meal. So,
when high carbohydrate is being intake inside the body this insulin and glucagon, whether
glucose the body needs glucose or high concentration of glucose is there, whether glucose is to
be converted to glycogen, these two hormones are balancing this particular thing. And this
is the regulation of p p p pathway. And as I have told you, that this particular by the
bi-product of this particular cell cycle, this metabolic pathway is playing significant
role in the different metabolic activities. Now, let us say that how glycogen is being
synthesized when glucose is more in the body, in the cell. How glucose is getting converted
and getting stored in the liver by this process? So, we will learn that how glucose is converted
to glycogen.
As in my earlier classes, I have told you that glycogen is the storage food material
in case of animals. Now here, if we see that structure of glycogen, then we can find that
glycogen is a polymer of glucose residues which are linked by alpha one four glycosidic
linkages and alpha 1 6 glycosidic linkages. Now, when this branching is there, then it
is alpha 1 6 glycosidic linkage.
Now here, in the liver I have told you the synthesis and break down of glycogen is regulated
to maintain the blood glucose level and in muscle the synthesis and break down of glycogen
is regulated to meet the energy requirement of the muscle cell. That means, it is playing
that the glucose or glycogen is playing a significant role to supply the glucose in
different parts of the cell and glycogen is being stored. The glucose in the form of glycogen
is being stored in the liver cell and then it is or muscle and it is being released and
glucose is giving energy to the muscle.
Now, when we are talking about the different stages of glycogen synthesis then we can find
that glucose is getting converted to glucose 6-phosphate. This step is same to that of
the glycolytic first step of glycolytic process. Here you see, hexokinase is the enzyme. One
molecule of ATP is needed to carry out this reaction to first phosphorylate this glucose
6-phosphate that for phosphorylation process ATP is needed. And for higher cell glucokinase
is playing a significant role for conversion of glucose to glucose 6-phosphate.
Glucose six phosphate this is a very interesting step way step for these particular pathway
of glycogen synthesis. Glucose 6-phosphate in the presence of phosphoglucomutase is getting
converted to glucose 1 6-bis-phosphate which is a very unstable intermediate product and
ultimately it is producing glucose one phosphate.
Now see, this is the structure this is the mutase enzyme which has got one phosphate
group within this structure of this enzyme. This mutase enzyme has got its phosphate group
within it. Now, glucose one phosphate is there. So, glucose 6-phosphate is getting with the
donation of this phosphate group from this particular mutase enzyme. It is becoming glucose
1 6-bis-phosphate. That means, one position and six positions are phosphorylated. This
product is a very unstable product and this enzyme once again taking back of this phosphate
from the 6th position of this phosphate, is being taken up by this enzyme and it produces
glucose one phosphate in this particular step.
Now, when glucose one phosphate is produced one phosphate in the presence of uridyl transferace
enzyme is producing UDP glucose. That means uridyl diphosphate. This uridyl diphosphate
in the presence of pyrophosphate, it is releasing two inorganic phosphate. Now here, in this
step once this UDP glucose is produced the synthesis of glycogen is taking place.
Now say, for glycogen synthesis, glycogenin protein is playing a significant role. Glycogenin
protein if we see the structure, we will find that this protein moieties has got one tyrosinase
residue. And in this tyrosinase residue we know that one aromatic ring and one hydroxyl
group is there with this tyrosin. And this tyrosin when it comes with this UDP glucose
which is produced in the earlier step, this UDP glucose and this protein glycogenin protein
undergoes this reaction and here this hydroxyl group is getting binded with a first carbon
of these glucose moieties and UDP molecules are getting released. And these core moieties
this glycogenin protein is getting attached with this glucose moieties of this UDP glucose.
Now, it becomes UDP and glucose is getting attached with this glycogenin protein. Now
this way UDP glucose is going on supplying, this particular reaction to go forward.
Now every time this UDP glucose is coming in contact with this particular bonding and
this fourth carbon you see it is free. And in this way this new, new residues are coming
and getting attached.
See UDP glucose is here and it is supplying this glucose to this chain and this UDP this
glucose is getting attached to this and UDP is being released out of this particular reaction.
That means UDP glucose is acting as the glucose donor to this and in this way the chain length
of this glycogenin and one end is attached to the glycogenin protein and this way the
chain length is getting increased. And it is getting attached with the this alpha one
four glycosidic linkages. Now, if we see the glycogen synthesis now this way the synthesis
is taking place within the cell. Now a glycosidic bond is formed between the
anomeric C 1 carbon atom moieties derived from UDP glucose and the hydroxyl thriosine
side chain of glycogenin UDP is released as a product. So, see this particular reaction
here which is there you see this here this first carbon, this is the first carbon, this
is the second carbon. So, first carbon is getting linked with the tyrosinase this is
the hydroxyl group and it is getting linked with the first carbon. The fourth carbon is
getting free and when another residue is coming then it is getting linked with the first carbon
of another glucose moieties. And in this way alpha one four glycosidic linkages is formed
with this particular reaction.
Glycogenin is then catalyzes that glycosylation at C 4 of the attached glucose with UDP glucose
again being the glucose donor. The product is and O linked disaccharide with an alpha
one four glycosidic linkage. This process is repeated until a short chain of glucose
polymer is produced and alpha one four glycosidic linkages is build up. Glycogen synthase is
the enzyme which catalyzes the elongation of the glycogen chain. That means, how been
this chain length will be. Glycogen synthase catalyzes the transfer of glucose moieties.
That means in presence of this glycogen synthase enzyme, the supply of UDP glucose is continuing
and chain length is being determined to the hydroxyl C 4 of the terminal residue of the
glycogen chain to form alpha one four glycosidic linkages. The branching enzyme transfers a
segment from the end of the glycogen chain to the 6 hydroxyl group of the glucose residue.
So, this 6 hydroxyl group of the glucose residue and from here the branching of alpha 1 6 linkages
starts which completes the actual glycogen structure. So, one is the linear chain another
is the branch chain. And here this branching is taking place and this way the glycogen
is getting synthesized in the cell.
Now, glycogen synthase is the regulatory enzyme in the synthesis of glycogen. That means,
in glycogens synthesis that enzyme glycogen synthase is playing a significant role. The
enzyme is regulated by covalent modification and phosphorylation.
Now, if we see the regulation of glycogen glycogen synthase enzyme, we can find that
when glycogen synthesis phosphorylated it is inactivated. That means in the non-phosphorylated
form of glycogen synthase is the active form. And when it is getting inactive, that means
it is phosphorylated. It is similar to that of glycogen phosphorylase enzyme which is
active upon phosphorylation and inactive upon dephophorylation. And that thus glycogen synthase
and glycogen phosphorylase are completely different in its activities. So glycogen synthase
is playing a significant role in case of glycogen synthesis.
Now if we see the glycogen synthesis, we can find out this glucose 6-phosphate becomes
glucose one phosphate. Glucose one phosphate in the presence of UTP produces this UDP glucose
and PP i. This pyrophosphate in presence of water is giving inorganic phosphate. UDP glucose
now it supplies this glucose moieties to the glycogen moieties and this glycogen become
glycogen in plus one. And in this way there’s number of UDP glucose is increasing the chain
length of glycogen moieties. Glucose 6-phosphate plus ATP plus glycogen n molecules of glucose
moieties plus water molecule gives rise to glycogen n plus 1 plus ADP plus 2 P i. The
only ATP is used to store one glucose residue in glycogen.
So, this is the glycogen synthesis in the cell. Now if we see the glycogen break down
that means, when the cell is in need of glucose then glycogen is once again chopped down to
glucose moieties. Now how it is taking place? Glycogenolysis is a catabolic process which
involves the breakdown of glycogen to glucose units. a The pathway of glycogen breakdown
was elucidated by the studies of cori and cori. The formation and break down of glycogen
regulates the blood glucose level in the body.
Three enzymes are playing a very important crucial role in this glycogen break down process
which is the glycogen phosporylase, glycogen branching enzyme that is branching enzymes
are once again divided into two; one is called the transferase, another is the alpha 1 6-glucosidase
and third is the phophoglucomutase.
Now these three enzymes are playing a significant role in this process. Now how this glycogenolysis
takes place? Now in the step one, what is happening? The sequential removal of glycosyl
residues from the non-reducing end of glycogen molecules takes place. Glycosidic linkages
between the glycosyl residues is split by the orthophosphor phopharic acid. That means
inorganic phosphate orthophosphate is playing a significant role. Enzyme responsible for
this step is glycogen phosphorylase which is activated by phosphorylase kinase. Now,
this particular enzyme is very important as far as the breakdown of glycogen is concerned.
In case of glycogen synthesis, glycogen synthase enzyme was playing the significant role. But,
here in during this breakdown process glycogen phosphorylase in the presence of phosphorlyase
kinase is playing a significant role.
In the first step of glycogenolysis, we can see this is the one for glycosidic linkages
n number of such chains are there. In presence of orthophosphate and in presence of glycogen
phosphaorylase enzyme this it is getting this inorganic phosphate is occupying the first
position of this glucose. Glucose one phosphate is produced and here n number of this n minus
one glycogen residues are remaining. Glucose one phosphate is converted to glucose 6-phosphate
which can further enter to the metabolic pathway. The enzyme responsible for this particular
reaction is the phosphoglucomutase.
Now phosphoglucomutase is converting glucose one phosphate to glucose 1 6-bis-phosphate
and ultimately it is producing glucose 6-phosphate. You see here, as I have told you that phosphoglucomutase
is a very interesting enzyme. It contains some phosphate group within this and when
you see glucose one phosphate has got already one phosphate in the first carbon and here
this phosphate is being donated to the 6th position of this glucose and it becomes a
glucose 1 6-bis-phosphate. This particular product is a very, very unstable product and
immediately. What this mutase enzyme is doing? It is taking up the phosphate group from the
first carbon and it go it taking back this phosphate group once again to it donating
this phosphate to the 6-phosphate. And glucose one phosphate becomes glucose 6-phosphate.
So this is the reaction which is going on inside the cell.
Now this reaction is a reversible in nature. Released sugar is phosphorylated. No investment
of ATP is needed because inorganic phosphate orthophosphate is donating this phosphate
group. No ATP is needed in this particular reaction required and can enter to the glycolysis
directly. The phosphorylated product of glucose one phosphate cannot leave the cell.
While coming to the step two; we can see that glycogen chain is attached to the core glycogenin
protein is degraded into a limited extend by this phosphorylase enzyme. It fails to
break the alpha 1 6-glycosidic that means, the branching chain; straight chain and brach
chain it fails to break the branching chain by this alpha 1 6-glycosidic bondings are
there. Phosphorylase enzymes stops the cleaving of alpha 1 4-linkages when it reaches the
terminal residue which is 4 residue away from the branching point. This is very interesting
mechanism. Now, glycogen branching enzyme transfers the
three glucose residue from the four residue glycogen branching to the nearby branch. Now
here see 2 points; phosphorylase enzymes stop cleaving alpha 1 4-linkages till the four
residues are left in this process.
That means you see this is the alpha one four linkages. This is 1 6 and the 1 4-linkages
are there and this track chain is going on and this phosphorylase enzyme is cutting down
this and releasing this glucose moieties free from this branch until and unless four residues
are left. As long as four residues are left. It stopped its cleaving. That means here a
1 6-linkages are there. What then it is doing now? What it is doing it is now enzyme that
is that, transfer the three glucose residues from the 4 carbon chain. That means, this
three carbon sugar is now getting cleaved by this enzyme and it is getting debranched
and coming and getting joined to the nearby chain. So here, from the four glucose residues
were there. Three glucose residues were debranched by the enzyme the transfer is and it transfered
these three moieties to this linear branch remaining this one glucose with this alpha
1 6-linkages are there. Now glycogen debranching enzyme a transfer
this glucose three glucose residues to the four residues glycogen branch to the nearby
branch it is getting joined. These leaves on the donor branch a single glucose residue
which is attached or connected to the main chain by an alpha 1 6-linkage.
Here, this one glucose moieties which is left this glycogen branching enzyme b is now cleaving
this 1 6-glycosidic linkages and making this glucose moieties free. And it becomes once
again the linear chain and linear chain once again it will start breaking this particular
glycosidic, this glycogen molecule and giving a continuous apply of glucose to the system.
Now if we see the overall reaction, then we can find that you say this is the glycogenin
protein which is attached to this glycogen and glycogen has got a one four and 1 6 linkages.
So, one four linkages are the linear and it goes on chopping in a normal position. In
case of 1 6, this 1 6 is the branching and there after once again this 1 4-linkages are
there. So it starts cleaving from the non reducing
end of this sugar. And as soon as 4 carbon moieties are there, it stops its cleavage.
When 4 carbon moieties are left, then phosphoryl this debranching this enzyme a is now active
and it cleave the three carbon residue from this 4 carbon sugar moieties and it comes
and getting attached to this main chain. This any straight 1 4-glycosidic linkage and here
one glucose molecule is remains attached to with 1 6 glycosidic linkage. Now, when this
1 6-linkage is this sugar moieties is left then, once again glycogen debranchaning enzyme
b is active and here it cleaves this 1 6 branching leaving this glucose moieties free from this
branching chain and glucose moieties are getting free. And in this way this breakdown mechanism
is going on inside the cell.
So we have learnt the glycogen synthesis, glycogen breakdown. This glycogen synthesis
and breakdown is totally dependent upon the concentration and the availability of glucose
within the cell. Now if we see, the fate of glucose 6-phosphate which is there, so we
can see that this glucose 6-phosphate which is produced from either glycogen, this glycogen
is converted to glycogen, glucose one phosphate. Glucose one phosphate is once again converted
to glucose 6-phosphate and this glucose 6-phosphate under goes different reaction where in a muscle
cell or in a brain cell through glycolytic process it under it is converted it is getting
oxidized to pyruvate further. In under anaerobic condition pyruvate is getting converted to
lacktate. Pyruvate can enter to the TCA cycle with the release of a molecule of carbon dioxide
and acetyl coa is formed and TCA cycle starts that enters to the respiratory chain. Glucose
6-phosphate inside the liver, in the presence of glucose 6-phosphatase enzyme is getting
dephosphorylated and it becomes this glucose. And this glucose can now come to this blood
stream and it can go to the different part of the cell and it supplies the energy. Glucose
6-phosphate can also enter to this pentose phosphate pathway where glucose 6-phosphate
we have learned that how it is converted to 5 carbon sugar, ribose sugar and NADPH. So,
this is the overall effect of glucose 6-phosphate in the cell.
Now if we see the glycogen synthesis and breakdown; we can find that these are reciprocally regulated
within the cell. Now if we see, this the hormone epinephrine it is activating adedylade cyclase
enzyme which is in the active, in inactive form. With the release of this epinephrine
hormone it becomes active and it is becomes adenylade cyclase. Once this enzyme is active,
ATP is converted to cyclic a m p. Cyclic a m p when warmed it once again activates the
inactive protein kinase a two protein active protein. Kinase a when protein kinase is active,
it is regulating this phosphorylase kinase of this enzyme. And this phosphorylase kinase
under goes this then it is active it is undergoing the phosphorylase v form inactive form to
phosphorylase a form. And when we have seen that in the in the in the cell when phosphorylase
a is active. That means glucose under starting condition when body needs glucose then this
particular breakdown process is to be taken place. And in this phosphorylated form we
have seen that this particular enzyme is very active. That means this when body is under
starving condition this epinephrine hormone is the indicator and which is just switching
on and switching off the different active and inactive form of this enzyme. And this
phosphorylation and body is now getting continuous supply of glucose which is getting chopped,
which is getting broken down to glucose from glycogen and this way this is controlling
this particular pathway. Similarly, the this particular when reaction
starts, that means we have to also stop this glycogen synthase. Glycogen synthase we have
seen that, when this glycogen synthase is there that means it is converting glucose
to glycogen. But, body is in demand of this glucose. So, we cannot use this particular
enzyme this enzyme to be active. So what it is doing? This adenylate cyclase it is coming
this protein kinase up to protein kinase is active. Protein kinase is now inactivating
the glycogen synthase which is synthesizing, which is utilizing this glycogen synthesis
process and it gets stopped. So glycogen, glucose to glycogen formation is getting stopped.
And here when this body is under high demand of glucose, this phosphorylase a enzyme is
active. So, chopping down process and the breakdown process takes place and supply of
glucose in the body is taking place.
So in conclusion, what we can do, tell? That glucagon is helping when the body is under
starving state it stimulates glycogen breakdown inhibits glycogen synthesis. And when high
glucose body is having very high glucose, this fed state the insulin stimulate glycogen
synthesis and inhibits glycogen breakdown so that further concentration of glucose in
the cell is getting controlled. And in this way this pentose phosphate pathway glucose
synthesis and glucose breakdown is taking place in the cell. And it is also being controlled
simultaneously within the cell system. Thank you very much.