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BIOCHEMISTRY Citric acid - Krebs - cycle
Presentation: Dedes Michael
Welcome to Biochemistry! We continue our lessons with 10th chapter...
...which containes the Krebs cycle.
The Krebs cycle is also known as Citric acid cycle.
Lets see the reactions that take place...
...with syntax forms and 3D molecular models.
As we saw in the Glycolysis chapter...
...Glycose turns to Pyrovate.
The next step, in aerobic enviroment...
...is the oxidation of Pyrovate, to Carbon Dioxide and Water.
First it must turn to Acetyl-CoA...
...and throught a series of reactions, known as Citric acid cycle...
...or Krebs cycle, the Pyrovate decarboxylates to CO2 and Water...
...like the final products of a chemical burn reaction.
Except from Pyrovate, which is the final product of Carbohydrates metabolism,...
...other products of the metabolism of lipids and aminoacids...
..oxidate throught the Citric acid cycle, to CO2.
So, this cycle is the common way of metabolism of all nutricion substances.
Like we said before,...
...the Pyrovate, in order to full break apart to CO2 and Water...
...first reacts with CoA, with ***+ and produces Acetyl-CoA.
The black portion of Provate, that you see here...
...produces a molecule of CO2, at this point.
A molecule of NADH is also produced.
The red portion of Pyrovate is the Acetyl part, that reacts with CoA...
...and produces the Acetyl-CoA, which has this syntax form.
The red part, here, is the Acetyl group, and the rest is the CoA.
All this molecule is the Acetyl-CoA...
...which we write briefly in this form.
This molecule of Acetyl-CoA will enter in the Cirtic acid,...
...so the Acetyl group can be fully decarbohylated to CO2.
Let see all the steps in Citric cycle.
In the first step, we have...
...one molecule of Oxaloacetate, which is the first substance that reacts in the cycle,...
...who takes place in mitochondrion.
We can see a different view of Oxaloacatate...
...so it shows easier how it will react with the next substance...
...which is the Acetyl-CoA...
...that produced in the previews step from Pyrovate.
That Acetyl group with the red color, over here...
...will connect with Oxaloacatate...
...and will produce the Citric acid.
From the 4 carbon molecule that we had before,...
...we now have Citric acid that have 6 carbon atoms...
...3 carbons connected with 3 carboxyl groups...
...and also a hydroxyl group in 2nd carbon.
So, in this reaction the Oxaloacatate turns to Citric...
...and the enzyme is: 'Citrate Synthase'.
The name of enzymes is not necessary for school (in Greece high school).
In the next step, we have the isomerisation of Citric acid.
We write the Citric acid in linear form to understand the reaction.
It has a hydroxyl group in the third carbon.
This hydroxyl group, moves to a neighbored carbon atom...
...and it produces the Isocitrate acid,...
...which has the hydroxyl group at 2nd carbon, as you see,...
...from the 3nd atom that hold it in Citric acid, next to this carboxyl group.
So this is Isocitric acid.
To produce the Isocitric acid from Citric acid the enzyme...
...'Aconitase' is needed.
In the third step...
...an oxidation and decarboxylation of isocitric acid take place at the same time.
The hydroxyl in this position, -with the blue arrow-...
...is oxidated to a ketone group, with a ***+ isoenzyme.
Of course the ***+ turns into NADH.
At the same time this carboxyl group that pointed...
...with the green arrow,...
...decarboxylate and a CO2 molecule is removed.
That turns the Isocitric acid into á-Ketogloutarate acid,...
...which has one less carbon atom, that you can see in 3D video...
...in the 3nd position...
...and in 2nd position has the double bond with oxyzen...
...which is at this point right here.
So, what we have in the third step?
We have the change of Isocitric acid to á-Ketogloutarate...
...a ***+ is turned into NADH,
...and production of one molecule of CO2.
The enzyme that makes this reaction is...
...'Isocitrate Dehydrogenase'.
Fourth step in the citric acid cycle.
An oxidation and decarboxylation of á-Ketogloutarate acid.
As we can see in the syntax form, the carboxylate group at this carbon...
...is oxidated with a molecule of ***+...
...(the ***+ will turn to NADH)...
...and at the same time is decarboxylated...
...and a molecule of CO2 is produced.
It also reacts with a CoA molecule...
...and Succinyl-CoA, is produced...
...which is all this big molecule right here...
...as it is connected with CoA which is realy hudge and...
...complicated molecule.
If we zoom in, only in the group that we want...
...we will see that at the top edge next to the S atom,...
...we have the 4 carbon atoms that you see also in the syntax form.
What we have here is that the á-Ketogloutarate acid...
...is turned into Succinyl-CoA,...
...a ***+ is turned to NADH,...
...as a molecule of CO2 is produced.
The enzyme is 'á-Ketogloutarate Dehydrogenase'.
With the production of Succinyl-CoA,...
...we have a high energy bond at this point.
So in this 5th step...
...we have the reaction between Succinyl-CoA and a molecule of GDP,...
...with the participation of a phospate group,...
...which is turned into GTP,...
...with the removal of CoA.
So the Succinyl-CoA is turned into Succinate acid.
From this point, at the citric cycle,...
...we will have 4 carbon atoms,...
...and as you can see, the Succinate acid...
...has two carboxylate groups at the 1st and at the 4th...
...carbon atoms.
At this 5th step, the Succinyl-CoA is turned into Succinate acid...
...and at the same time a GTP is produced.
The enzyme is: 'Succinyl-CoA synthetase'.
In the 6th step we have the oxidation of the Succinate acid.
At this point, as arrow shows, a FAD molecule is turned to FADH2...
...oxidates the Succinate acid, producing a double bond...
...between these two carbons...
...which changes Succinate acid to Fumarate acid.
We see the Fumarate acid in the 3D shape...
...is a flat molecule, which has...
...two carboxylate groups at 1st and last carbons and a double bond here.
So here, we have Succinate acid to turn into Fumarate acid...
...and the production of a FADH2 molecule.
The enzyme is: 'Succinic dehydrogenase'.
The Fumarate acid is hydrated, in this 7th step,...
...so the double bond, over here, will take...
...one molecule of water. By addition reaction...
...one hydrogen will be added to one of these carbons...
...the hydroxyl will de added to the other...
...so the Foumarate acid, after the addition of water,...
...will be changed into Malate acid.
You can see the syntax form here, which it has...
...the hydrogen to the one of the ex double bond carbons...
...and the hydroxyl to the other.
This is the Malate acid in the 3D form, and at the back side...
we can see the hydroxyl group. Here is the oxyzen and here the hydrogen.
Here we have the Foumarate acid turned into Malate acid.
The enzyme is: 'Foumarase'.
Here is the last reaction in Citric acid cycle.
The Malate acid is oxidated.
From the syntax form we can see, here at 2nd spot,...
...that there is an hydroxyl group.
This group is oxidated from a ***+, which is turned to NADH,...
...and is changed to ketone group.
This reaction turns Malate to Oxaloacetate acid,...
...and by this we will return to the first molecule of Citric acid cycle.
This is the ketone group at the 2nd atom with the double bond...
...between carbon and oxygen.
In this step, Malate acid is turned into Oxaloacetate acid,...
...with the enzyme: 'Malate dehydrogenase'.
Let see the energy efficiency of Krebs cycle.
In the first reaction Oxaloacetate is turned into Citric acid,...
...which gives the name to the cycle as it is the first product of the cylce.
We haven't any usefull molecule production here.
Lets go to the second step.
We have the Citric acid turning into Isocitric.
No usefull molecul production, either in this step.
In next step, it is turned into á-Ketogloutarate acid,...
...and we have the production of a NADH molecule,...
...and a CO2 molecule at the same time.
In the next step,...
...the á-Ketogloutarate acid is turned into Succinyl-CoA,...
...a 2nd NADH molecule is produced...
...and also a 2nd CO2 molecule.
The Succinyl-CoA is turned into Succinate acid...
...and a molecule GTP is produced at the same time.
The Succinate acid is turned into Fumarate acid,...
...and a FADH2 molecule is produced.
Malate acid is produced from Fumarate acid...
...without any usefull molecule production.
Oxaloacetate acid is produced from Malate acid,...
...with production of a 3nd NADH molecule.
Finally,...
...in the Krebs cycle...
...we have production of 3 molecules of NADH...
...1 molecule of FADH2...
...and 1 molecule of GTP.
Every NADH molecule is equal to 3 molecules of ATP,...
...so we have 9 ATPs from here,...
...one FADH2 molecul is equal to 2 molecules of ATP,...
...and one molecule of GTP equals to 1 molecule of ATP.
Total we have 12 molecules of ATP in one Citric acid cylcle.
We hope that with these reactions...
...and with the syntax and 3D forms...
...to make more unterstandable the Krebs cycle...
...in the mitochondrion.