Good morning students. In our earlier classes we have discussed very many cycles path way
and we have also learnt that how respiratory process that catabolism is going on in any
living system. Today, we will be learning another new pathways, pathway which is going
on inside any living cell and it is playing a very important role as per as the living
system is concerned. And that is called the urea cycle. And today I will start with this
urea cycle followed by gluconeogenesis and it will be ended with glyoxylate path way.
So, let us start with urea cycle. Now urea cycle is otherwise known as ornithine cycle.
The biochemical reaction which is going on in every living cell including that animal
being and that produces urea from ammonia. This cycle is the first metabolic cycle discovered
by Hans Krebs and Kurt Henseleit in the 1932. In this particular cycle what we will be learning?
We will be seeing that how urea is being produced in the living system.
Now, ammonia which is released mostly by this living, by this amino acid is broken down
in the liver. Some of this ammonia is used in the biosynthesis of nitrogenous compound
and the remaining excess ammonia mainly present in the form of ammonium ion is found to be
toxic and at high concentration in the living system if it starts getting accumulated. It
has been seen that it causes brain damage. So, this particular bi product which is produced
inside the cell is to be removed. And how it is removed? It is removed through this
urea cycle.
So, ammonia has to be effectively removed from the cell because of this toxic effect.
This removal of this ammonia takes place in the following way: Incase of aquatic animals,
so I in the beginning only I have told you that in any living system this type of urea
cycle is present. So, incase of the aquatic animal, mainly these bony fishes; it directly
excretes ammonia into the surrounding water and this group of animals are called ammonotelic
animals. That means this are these are the group of animal they are secreting ammonia
directly to the surrounding and it is going out of the body system. Incase of terrestrial
vertebrates, including human so incase of our system what we do? How we excrete? It
is getting excreted in the form of urea and this is and these groups of animals are called
ureotelic animals. Incase of birds and reptiles where they convert this ammonia to uric acid
before excretion and that group of animals are called uricotelic animals.
So, these are the different variations. So, what we have learnt? We have learnt that this
ammonia can directly be released from the body. It may be converted to urea or it may
be converted to uric acid to the surrounding environment and it is going out of the system.
And when such type of metabolism and when such types of processes are going on inside
the system, we are we are detoxifying our body from this toxic accumulation. Today,
we will be learning how urea is being excreted from the system living system.
Now, if we see the structure of urea, it is the diamine of carbon, very simple structure
that is two amino group here attached to this C double bar O. In contrast to ammonia, which
is basic in nature urea is neutral and hence it is non toxic in nature. It is easily transported
in blood and excreted in urine. Urea is produced in a cycle sequence of the reaction called
as urea cycle. Its location if we see the location of this urea cycle then, in the lever
cell and sub cellular location that is if we further classify then, we can find that
it is partly taking place in the mitochondria and partly it is taking place in the cytoplasmic
fluid of the cell. So, you just see incase of glycolytic process we have seen that glycolysis
is taking place in the cytoplasmic fluid. Mitochondria is taking place in the, this
TCA cycle is taking place in the mitochondria. But, you see this urea cycle which is taking
place in partly in the mitochondria and partly in the cytoplasmaic fluid. So, this is the
particular cycle. Now, here if we see come in comparison to the other metabolic path
ways, what we already learnt that glyocolotic pathway when I discussed I told you that this
process is the ten steps process. In case of TCA cycle, I told that TCA cycle is the
eight steps process. And in each step we have seen that the roles of precursors are immense.
We cannot ignore.
In this particular urea cycle also we have seen that precursors are playing a significant
role in the five step process of urea cycle. Now, these precursors are carbon dioxide in
the form of bicarbonate. This nitrogen, how nitrogen nitro groups are coming? One is directly
derived from the ammonium that is N H 4 plus and second one is coming from the amino acid
that is, the aspartate. ATP molecules are playing a significant role in this urea cycle.
Incase of that respiratory process we have seen that how ATP molecules are generated
when this catabolic process is going on in the living system. Here, we will be seeing
that how ATP driven process is also simultaneously going on in the living system. And urea cycle
is one of such example. Now here, ATP is needed to carry forward this reaction. Water molecule
is also playing a significant role in urea cycle.
Now, as I have told you that urea cycle is a five step process and here different enzymes
are playing very important role in this particular cycle. If we see the different enzymes we
can find that carbamoyl phosphate synthetase one, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinate
synthase, argininosuccinate lyase and arginase enzymes are playing a vital role in this urea
cycle.
Now, at a glance if I give you the overview of this urea cycle then we can see that, initially
this ammonium ion and bicarbonate in presences of two molecules of ATP is produced carbamoyl
phosphate. And this carbamoyl phosphate is the first product of urea cycle. This particular
reaction is taking place in the presence of the enzyme called carbamoyl phosphate synthase
one. This particular reaction when it is going on, it produces two molecules of ADP and inorganic
phosphate. This particular step is going on inside the mitochondria of the cell. When
we are coming to the second step, carbamoyl phosphate and ornithine which are already
present in the mitochondria, it is producing citrulline and one inorganic phosphate in
the presence of ornithine transcarbamoylase. And here this step also taking place in the
mitochondria of the cell. As soon as citrulline is produced, citrulline is going out of this
mitochondria and it is coming to the cytoplasmic fluid of the cell. And citrulline in presence
of aspartate and one molecule of ATP is needed to go forward this reaction and it is producing
argininosuccinate and one AMP and inorganic phosphate. In the presence of this enzyme
argininosuccinate synthase and this reaction as I have mentioned that it is taking place
in the cytoplasmic fluid of the cell. Argininosuccinate in the presence of argininosuccinate lyase
this is the reaction when lytic process, breakdown process going on and it is once again forming
this arginine and fumarate and it is taking place in the cytoplasmic fluid of the cell.
Arginine in presence of water once again gets converted to ornithine and urea. Urea is going
out of the system and ornithine from the cytoplasmic fluid is once again entering to the mitochondria
to carry out this cycle. And this way continuously this cycle is going on inside any living system
and urea is generated and going out of this living system.
Now, I have told you the overview of this reaction. Actually how these reactions are
going on? This is a very simple pathway and here as I have told you the overview and then
we will come systematically each and every step and how this product and bi products
are produced, we will also see and learn. See here this carbon dioxide and ammonia in
presence of two molecules of ATP producing this ADP and P i and carbamoyl phosphate is
produced. See this carbon dioxide which is donating this bicarbonate and this ammonia
see here ammonia is there.
See this ammonia in the form of ammonium ion two molecules of ATP and one water molecule
is yielding carbamoyl phosphate along with the production of 2 ADP P i and 3 hydrogen
molecule. So, this is the first step of urea cycle.
Now here, you see carbamoyl phosphate synthase enzyme is playing a significant role in this
conversion process. Now, when this is getting converted it is this carbamoyl phosphate is
produced. This carbamoyl phosphate in presence of ornithine is converted to citrulline and
the enzyme which is playing a significant role is the ornithine carbamoyl transferase.
So here, you see this is producing this citrulline. This process up to this process it is going
on in the mitochondria of the cell. Here, as soon as citrulline is produced, citrulline
in presence of aspartate in and the enzyme argininosuccinate synthase is getting synthesized
in presence of one molecule of ATP and producing argininosuccinate. Argininosuccinate when
it is produced in the presence of the enzyme argininosuccinate lyase is once again splitted
into arginine and fumarate. This fumarate is I, we know that this fumarate is one of
the bi product of TCA cycle. So, this fumarate is entering to the TCA cycle and this arginine
which is another product of this particular cycle goes forward at in the presence of this
enzyme arginase it releases this urea from it and another product ornithine. This ornithine
is once again entering to this mitochondria of the cell.
Now, let us come step wise to this particular reaction that how these reactions are going
on and how the intermediate products and bi products are produced? In the first step we
have learned that bicarbonate and ammonium ion combine to form cabamoyl phosphate.
So, we have already learnt this carbamoyl phosphate formation where this bicarbonate
that is H C O 3 minus which is contributed by this carbon dioxide and from this ammonia
this ammonium ion is coming. So, these two products when they are coming, this bicarbonate
you see, this is the bicarbonate and when ATP molecule I told you that two molecules
of ATP are needed. This is two molecules of ATP. So, first molecule ATP is coming and
it is donating its phosphate group and it is producing carboxyphosphate. You see this
phosphate group is donated by this ATP and ADP production is there. That means this bicarbonate
is getting converted to carboxyphosphate. Now here, when carboxyphosphate formation
is there then ammonia in the form of ammonium ion is coming and playing a significant role.
Now, this ammonia is coming and it is forming the carbamic acid. That means this carboxyphosphate
now once again become this removal of phosphate group is taking place and it becomes carbamic
acid. When this carbamic acid is formed, another molecule of ATP is coming and donating its
phosphate to this carbamic acid and ultimately you see this carbamoyl phosphate is formed.
You see this is the phosphate and this is the carbamoyl group and carbamoyl phosphate
is produced which is the end product of this first step of urea cycle. Now, if we sum up
then this step comprises the three sub steps where phosphorylation of bicarbonate forms
the carboxyphosphate this is the first step. Reaction with ammonium ion with the carboxyphosphate
to form carbamic acid this is the second step. And finally, once again this carbamic acid
is getting phosphorylated. And finally, phosphorylation of carbamic acid to carbamoyl phosphate is
taking place. So, we can see that this reaction what we have seen that though it is showing
a single step reaction but, in reality it is a complex reaction where three sub steps
are needed, where bicarbonate is converted to caboxyphosphate. Caboxyphosphate is converted
to carbamic acid and once again ultimately carbamoyl phosphate is produced.
Now, when this carbamoyl phosphate is production is over then this second step, this is the
second step. In this step two what is happening? This carbamoyl phosphate is reacting with
the ornithine. See this is the ornithine which is there in mitochondria is coming in contact
with this carbamoyl phosphate and it is producing the citrulline.
Now here, in the second step carbamoyl residue is transferred to ornithine forming citrulline.
That means this is a carbamoyl residue. These carbamoyl residues are getting transferred
to this ornithine group and this ultimate result is the formation of citrulline. This
reaction is catalysed by ornithine transcarbamoylase enzyme. Citrulline is passed into the cytoplasm
via the transporter, the transport system which is there.
The citrulline, now also this citrulline which is produced is in the mitochondria of the
cell and this citrulline is now coming through transporter to the cytoplasmic fluid of the
cell, now this transportation of this citrulline is taking place. So, in this step what we
have seen? We have seen that carbamoyl phosphate this this carbamoyl group is being transferred
to ornithine and citrulline is formed.
Now, in the next step what is there? That aspartate is condenses with this citrulline
forming argininosuccinate.
Now, if we see this citrulline which is the end product of the second step. In the step
three what is happening? This citrulline in presence of aspartate that condensation reaction
is going on in presence of one molecule of ATP which is producing one AMP and inorganic
phosphate and argininosuccinate is produced. This reaction is catalysed by argininosuccinate
synthetase enzyme. Now, here we can see that here this transfer of this group is taking
place and amino group of the this aspartate is going and getting binded and the new group
is getting connected with the citrulline producing argininosuccinate. This is the condensation
reaction.
Argininosuccinate in the next step is getting cleaved. Now, this argininosuccinate is once
again producing this separating this arginine from the fumarate.
Now, you see here this it is that step four. In the next step what is happening? This argininosuccinate
in the presence of lyase enzyme argininosuccinate lyase it breaks this bonding and you see here
this arginine it is one amino acid arginine. See here this amine groups are getting separated
and fumarate which is one of the bi product of TCA cycle is being released and this fumarate
can enter to the TCA cycle for subsequent utilization.
And in the last step what is happening? In step five what is happening? This arginine
in the presence of the enzyme arginase is getting converted to urea and ornithine. The
hydrolysis of arginine generates urea at ornithine. Now, see here this group is being separated
and urea is produced and ornithine is once again going and entering to the mitochondria
for urea cycle.
This reaction is catalysed by this arginase inside. Ornithine is transported back to mitochondria
for the next cell cycle.
Now if we see this urea cycle, it can be linked with the citric acid cycle. As I have already
mentioned you, that urea cycle during this urea cycle we have seen the generation of
fumarate which is one of the intermediate of TCA cycle. Each cycle though operates independently
but, are connected depending on the transport of intermediates. Fumarate get gets converted
to malate in cytosol by fumarate dehydrogenase that is one of the isoenzyme and then it is
transported to mitochondria where it takes part in that TCA cycle. So, in the mitochondria
this fumarate takes part for citric acid cycle. Aspartate in mitochondria can be transported
to cytosol and it takes part in the urea cycle.
Now here, whatever I have told if I sum up then, we can find that you see here carbamoyl
phosphate in the presence of ornithine is producing citrulline. As soon as citrulline
see this is the cell and this is the mitochondria and this is the cytoplasmic fluid. So, citrulline
is produced. Citrulline is getting transported out of this mitochondria to the cytoplasmic
fluid. This citrulline is now producing argininosuccinate. Argininosuccinate when it is cleaved it is
producing arginine and fumarate. So, this fumarate is entering to this TCA cycle back
to this mitochondria. Fumarate may get converted to malate and this malate can once again come
and enter to this TCA cycle. And this particular reaction we can tell that aspartate argininosuccinate
shunt for citric acid cycle which is a bypass reaction. And here this arginine which is
produced is releasing urea and ornithine. And ornithine is transported into mitochondria
and this urea cycle is getting completed and this is all about this urea.
Now, coming to this regulation; the enzyme carbamoyl phosphate synthetase one is allosterically
activated by N-acetylglutamate. This one of the very important product which is controlling
the activity of carbamoyl phosphate synthetase one. Steady state level of N-acetylglutamate
is determined by the following: that is the concentration of glutamate and acetyl coA
that is one way and another is the arginine; which is considered to be the activator of
N-acetylglutamate synthase enzyme. So, these are the two important regulators. If we see
this acetyl coA and glutamate we can find that in the cell acetyl coA is produced with
fatty acid oxidation and beta oxidation.
So there here, we can get acetyl coA and glutamate is one of the amino acid which present in
the cell is undergoing reaction with inside with the help of the enzyme in acetylglutamate
synthase and it is producing the enzyme called N-acetylglutamate. This N acetylglutamate
and here arginine is also playing an important role to catalyze this reaction. Now, this
N-acetylglutamate is playing a significant role as it is the regulatory enzyme for carbamoyl
phosphate synthetase one. Now, this product undergoes several unknown reaction and ultimately
it is coming and it is just activating this enzyme and this bicarbonate and ammonia in
the presence of this enzyme is getting converted to carbamoyl phosphate which is the initial
product to start the urea cycle. And this way this N-acetylglutamate is controlling
this or accelerating the rate of carbamoyl phosphate production in the cell.
Now if we see the energetic, then we can find that ammonia, carbon dioxide, aspartate three
molecules of ATP 2 molecules of water gives rise to urea fumerate. Two molecules of inorganic
phosphate, AMP and pyrophosphate and thus in the entire cycle we can find that ATP,
3 molecules of ATP are used up. It is needed to carry forward this reaction. Two molecules
of ATP is being used in the first step and one molecule of ATP is used during the formation
of argininosuccinate and that is here it is the energy driven process.
Now if we see the urea cycle disorder, then we can find that an urea cycle disorder or
urea cycle defect is the genetic disorder caused by a deficiency of one of the enzymes
in the urea cycle which is responsible for removing the ammonia from the blood stream.
That means here with the defect that accumulation of toxic substances in the form of ammonia
is there inside the living system. The nitrogen accumulates in the form of ammonia, a highly
toxic substance and is not removed from the body. Urea cycle disorders are included in
the category of inborn errors of metabolism.
Now how to know? It can be this disorder can be recognized by very many ways. We can measure
some of the end product in the plant and as I have, we have already learnt that this urea
cycle is taking place either in the mitochondria or in the cytoplasm partly in the mitochondria
and partly in the cytoplasm. So, here what is there if this N-acetylglutamate synthase
enzyme is not there, then it is called N-acetylglutamate synthase deficiency. If this deficiency is
there then ammonia concentration in a blood is going up. Carbamoyl phosphate synthase
one and if this particular enzyme is not there then also it is called carbamoyl phosphate
synthase one deficiency. And here also this ammonia concentration is going up. Ornithine
transcarbamylase, this is another enzyme and if that disorder is there then we are calling
ornithine transcarbamylase deficiency and here it is resulting in the higher concentration
of ornithine urea orotic acid in the blood. In the cytoplasmic, when we are considering
the cytoplasmic enzymes then argininosuccinate synthetase enzyme and if it is not there its
deficiency is called citrullinemia. And here citrulline concentration in the blood is getting
up. Argininosuccinate lyase if not there it if it is deficient then it is called A L deficiency
or argininosuccinate acid urea deficiency. And here, citrulline argininosuccinate acid
concentration in the living system is going up. If arginase enzyme is deficient, arginase
enzyme is not there that is called argininemia. And here arginine concentration in the body
is going up.
Now to treat such type of patients; for treatment what we are, we have we have to do by we are
doing here the patient who are suffering from such type of diseases we have to give a controlled
diet where this protein intake should be minimum, where because there should not be much protein
that that can generate excessive ammonia which is formed out of this protein molecules. This
protein restriction is used in conjunction with the medication which provides alternative
pathways for the removal of ammonia from the blood. Frequent blood testing are required
to monitor the disorder. Optimize treatment and frequently hospitalizations are necessary
to control these disorders. At the most the extreme cases a few liver transplantation
has been taken place successfully to cure this disorder.
Now, if we come to this particular disorder and if we see this urea cycle we can find
that these amino acids are playing a significant role in this particular cell cycle, in this
urea cycle.
And if we see the different families; that is C 4 family conversion into oxaloacetate
and if we see we have seen that in Nacetylglutamate is playing a significant role in operating
this carbamoyl phosphor phosphate synthetase one. So, that enzyme which is there that glutamate
is playing a significant role. So, if we see inside the cell how we can tell this aspartate
and alpha ketoglutarate aspartate is the amino acid? And alpha ketoglutarate is one of the
intermediate products of the TCA cycle? When they undergo some reaction they produce oxaloacetate
and this glutamate which is playing a significant role in that supplying that N-acetylglutamate
formation.
If we see that C 5 family conversion into alpha ketoglutarate through gluatamate, we
can find that glutamine, proline, arginine, histidine they all are amino acids. They are
converting to converted back to glutamate. When glutamate is there, glutamate is getting
converted to alpha ketoglutarate and this is this way this alpha ketoglutarate and glutamate
is playing a significant role to operate this urea cycle.
Now coming to this another important amino acid which is also playing a significant role
in this particular glutarate production, we can find that this conversion of histidine
into glutamate. Histidine is also another important amino acid which is present in any
living system and it has got one imidazolium group. And this imidazolium group is present
in histidine which makes it unique from any other amino acids and where it under goes
some reaction ultimately we can find that, this glutamate is produced from this histidine
molecule. And this way this glutamate concentration in the cell is being maintained by very many
pathways from where this urea cycle or the intermediate this glutamate which is one of
the important intermediate for this urea cycle operation. And this way this urea cycle is
being operated inside any living system.
Now, coming to another topic that is the gluconeogenesis. Now here in my earlier class I have already
discussed the synthesis of glucose that glucose is being produced. And I have told that how
glucose to glycogen and glycogen to glucose production is taking place. are Or this type
of conversion that excess glucose is there it is converted to glycogen body is in need
of glucose glycogen is broken down to this glucose molecules and this way this glucose
generation is there from this carbohydral moieties. That I have already discussed in
my last class. But, today I will be discussing that another pathway that how glucose can
also be produced from non carbohydrate source. Now see, that gluconeogenesis is the synthesis
of glucose from the non carbohydrate precursors that is pyruvate lactate glycerol and amino
acids. So here, we can see that not only this carbohydrate but, the non carbohydrates are
also playing a significant role as far as this glucose production inside the cell is
concerned. It is one of the two main mechanism the body uses to keep blood glucose level
from dropping too low. That is when blood glucose is dropping down it is called hypoglycemia.
The other means of maintaining blood glucose level is through the degradation of glycogen.
What I have already discussed and how glycogen is being chopped broken down to glucose that
we have already learnt. Now, today we will be learning that from non carbohydrates source
how glucose is being generated. In animals the gluconeogenesis pathway is for the most
part the reverse of glycolysis. There are substitute or bypass reactions for the irreversible
steps of glycolysis. Sometimes what we have learnt in glycolysis? Glucose is converted
to pyruvate. But, we can say here that pyruvate is one of the precursors for gluconeogenesis.
So, from pyruvate when glucose is produced, it is just opposite to that of this glycolytic
process. But, in actuality it is not totally like that. Because some of the reactions which
are taking place and which are non reversible irreversible in nature those type of reactions
are bypassed in gluconeogenesis. Now, let us learn that what are those bypass
reactions which are there in gluconeogenesis. Now here, as I have told that pyruvate to
glucose is the gluconeogenesis.
Now, if we start from the end product of the glycolysis that is pyruvate. Now, pyruvate
in presence of pyruvate in in in the presence of the enzyme pyruvate carboxylase and one
molecule of ATP is being required and this bicarbonate is needed to convert this thing
to ADP. Now, gluconeogenesis begins in the mitochondria with the formation of oxaloacetate
through carboxylation of pyruvate. This reaction also requires one molecule of ATP and is catalyzed
by pyruvate carboxylase. This enzyme is stimulated by high level of acetyl coA that is, production
in beta oxidation in the lever and inhibited by high level of ADP. Oxaloacetate then converted
to phosphoenol pyruvate by the enzyme phosphoenol pyruvate carboxylase. So, pyruvate is getting
converted to oxaloacetate. Oxaloacetate is then in the presence of carboxykinase enzyme.
This enzyme is converting this oxaloacetate to phosphoenol pyruvate. And one molecule
of GTP is converting converted back to GDP and one molecule of carbon dioxide is being
produced in this particular reaction. That means this is the decarboxylation reaction
which is going on while conversion of oxaloacetate to phosphoenol pyruvate.
This is first step that is the bypass which is not there in case of glycolytic process.
In the second reaction, if we see the second bypass reaction of gluconeogenesis then, we
can find that fructose 1 6-bisphosphate. In the presence of this enzyme fructose 1 6-
bisphosphatase is converting converted back to ADP to ATP. That means from this first
phosphate that first carbon of this fructose which is phosphorylated, this dephosphorylation
is going on and from the first carbon, phosphate group is being taken up and ADP is ADP to
ATP formation is taking place and fructose 6-phosphate is produced. This particular step
is also otherwise is known as rate limiting step of gluconeogenesis.
In the another bypass reaction, where we can see that glucose 6-phosphate is once again
dephosphorylated and it is converted back to glucose in the presence of this enzyme
glucose six phosphate. Here also, we can find that this molecule of ADP with the uptake
of this this phosphate group is converted back to ATP. Now, the final reaction of gluconeogenesis
is the formation of glucose which occurs in the lumen of the endoplasmic reticulum where
glucose 6-phosphate is getting hydrolyzed by this glucose 6-phosphtase inside and glucose
is being produced as final resultant product. Glucose is shuttled into the cytoplasm by
glucose transporters located in the membrane of the endoplasmic reticulum.
And this is the bypass reactions and remaining that the other reactions which are there inside
this are same as that of this glycolytic process. So, if we see this reversal of this particular
this particular reaction we can find that this pyruvate is getting converted to glucose
and here is this bypass reaction. And these bypass reactions are different from that of
this normal conventional reaction.
Now if we see the glycolysis, gluconeogenesis and the pentose phosphate pathway; the main
regulation of this pathway occur in connection with this glucose 6-phosphate and this pathway
interacts with atleast two other pathways. Regulation of the pathways around glucose
six phosphate is important. Glucose six phosphate and or fructose 6-phosphate are allosteric
inhibitors of hexokinase that is depending upon or glucokinase that is the depending
upon the tissue. Insulin activates glcolysis, glycogensis and the pentose phosphate pathway
but, reduces gluconeogenesis.
And these are the some of this differences and similarities. If we see the stoichiometry
of gluconeogenesis then we can find that, 2-pyruvate from 2-pyruvate one molecule of
glucose is being produced and this reaction is thermodynamically this thermodynamically
this is possible and feasible. In contrast, the stoichiometry of this reversal of glycolysis
is thermodynamically unfavorable reaction where delta g is coming, the positive eighty
four kilo joule per mole. So here also, pyruvate is getting converted to glucose.
So this isthese are some of the differences in gluconeogenesis and glycolytic process.
So, these are this bypass reaction this fructose 6-phosphate to this glucose formation fructose
1 6- bisphosphate. Here this is one of this reaction phosphoenol pyruvate is another bypass
reaction and this glucose formation is the third step which is not similar to that of
glycolytic process. And here are the dissimilarities of gluconeogenesis and glycolytic process.
If we see that gluconeogenesis is taking place in the lever and in the muscle glycolysis
is taking place now glucose is getting converted to pyruvate to lactate. And then this lactate
is being enter to this lever cell and from lactate to pyruvate and pyruvate to once again
glucose is produced in the process through the process of gluconeogenesis.
And this glucose is once again coming to this once again coming to the muscle cell of the
body. Oxaloacetate utilizes the cytosol of this gluconeogenesis. Cytosol for gluconeogenesis
is formed in the mitochondrial matrix by carboxylation of pyruvate. Oxaloacetate leaves the mitochondria
by a specific transport system in the form of malate which is reoxidized and oxaloacetate
is formed in the cytosol. So, this is the pyruvate pyruvate to oxaloacetate
to malate and once again this malate is coming to the cytoplasmic fluid and malate to oxaloacetate
is produced and this way mitochondria and the cytosol these reactions are going on.
This is as I have already discussed. This is the reversal of this glycolytic and gluconeogenesis
process. Now, if we see the similarities and dissimilarities of this glycolysis and this
gluconeogenesis, we can find that here three enzymes which are participating in the glycolysis
process is different from that of this gluconeogenesis.
Hexokinase here it is in glycolytic process, here glucose 6-phosphatase phosphofructokinase
fructose 1 6-bisphosphatase and pyruvate kinase. This pyruvate carboxylase or phosphenolpyruvate
carboxykinase these are the enzymes.
And if we see the C 5 family conversion to this pyruvate, we can find that alanine and
alpha ketoglutarate is producing this pyruvate. This pyruvate can also be produced from this
amino acid. Different amino acids like alanine serine tryptophan glycine and ultimately with
this cysteine threonine and amino acetone are there. And ultimately you can see this
pyruvate is produced and this pyruvate, from this pyruvate once again this gluconeogenesis,
that glucose generation may also take place in the liver cell of the body.
Now coming to this last this another cycle that is, the glyoxylate cycle glyoxylate cycle
is an anabolic pathway which is occurring in the plant and several microorganism. This
pathway thus allows the cell to obtain energy from the fat. It utilizes acetate from fat
for biosynthesis of carbohydrates, the glyoxylate cycle whose initial reactions are identical
to that of this TCA cycle. So here, we can find that this acetate is getting converted
to citrate, citrate to isocitrate and then isocitrate that other reactions which are
there which is forming this succinate and glyoxylate which is entering once again to
this particular cycle.
This gltoxylate cycle in plant is taking place in the glyoxyzone of the cell.
Now see, acetyl coA in the presence of this particular acetyl coA in presence of oxaloacetate
is converted to citrate. This citrate is getting converted to isocitrate. You see this, after
this reaction it is similar to that of this TCA cycle. As soon as isocitrate is produced
it is producing succinate and these six carbon is broken to four and to this glyoxylate.
And here another molecule of acetyl coA is needed to produce this malate and once again
oxaloacetate is formed. And in this way when we see this particular path way we can find
that this TCA cycle, this glycolytic process, TCA cycle, urea cycle, glyoxylate pathway,
this gluconeogenesis and all this pathways which are simultaneously going on inside the
cell are playing a significant role. And how we have seen the one intermediate products
are been utilized for one pathway to another through the shuttle system. And this way in
a very complex reaction, N number of reaction reactions are simultaneously going on inside
the cell inside the living system. Thank you very much.