Hey this is Dr K from iMedicalSchool and today we are going to discuss the Kreb's so sit

back relax and lets get started.

We highlighted in our previous videos the process of gylocylsis and pyruvate decarboxylation.

Today we will talk about the Kreb's cycle which takes place in the mitochondrial matrix.

As we go along I would either draw out the Kreb's cycle and make notes or print out the

diagram we have provided from the link in the description and make notes on that.

After the end of glycolysis pyruvate is converted by pyruvate decarboxylase complex to Acetyl

CoA and CO2.

In the process an NAD molecule picks up a hydrogen with the release of another hydrogen.

The Acetyl CoA combines with oxaloacetate by the enzyme citrate synthase to produce

citrate but in the process the CoA of Acetyl CoA is released and a water molecule is consumed.

One of the uses of oxaloacetate besides as a reactant in the Kreb's cycle is that it

can be converted into one of th e 20 amino acids.

Oxaloacetate can be converted into aspartic acid by transamination.

In terms of Kreds cycle regulation, Citrate synthase is activated by ADP but inhibited

by ATP, NADH, and succinylCoA.

In addition, the citrate produced inhibits phosphofructokinse, an enyme that facilitates

a rate limiting step of glycolysis.

The reason that this occurs is that the body does not want to create too much ATP if it

is not needed so the more citrate is produced this creates a negative feedback on the glycolysis

pathway to prevent energy production.

The next step is really two steps in one.

First citrate isomerizes to cis aconitate and eventually to isocitrate via the enzyme

aconitase.

The next step is another two step reaction in one.

Isocitrate is acted on by isocitrate dehydrogenase to form oxalosuccinate.

Remember dehydrogenase enzymes always involves removal of hydrogens.

During this process NAD picks up two hydrogen atoms.

This step is completely irreversible and is one of the rate limiting steps of the TCA

cycle.

This step also produces the first carbon dioxide of the cycle.

The production of NADH is very important because the loading of these hydrogen carriers will

act as our drivers of energy production in the electron transport chain.

Oxalosuccinate is acted on by isocitrate dehydrogenase to alpha-ketoglutarte.

One molecule of carbon dioxide is produced.

Alphaketoglutarte is another TCA intermediate that can be converted into an amino acid.

It can be transaminated into glutamate.

Realize any intermediate that can turn into an amino acid, can also be created from their

respective amino acid.

For example if your body needs energy it can also use protein in rare circumstances.

In this case the amino acid glutamate can be broken down by glutamate dehydrogenase

into alphaketogllutarate and enter the TCA cycle.

Alphaketoglutrate is converted by alphaketoglutarate dehydrogenase complex to succinyl Coa.

In this process CoA is added and produces the second carbon dioxide molecule of the

cycle, as well as, an NADH with a hydrogen molecule is produced.

As part of the enzyme complex, cofactors such as thiamin pyrophosphate, lipoid acid, FAD,

NAD, and coenzyme A are required for this step The alphaketoglutarate dehydrogenase

complex is inhibited by ATP, GTP, NADH, and succinyl CoA.

It is activated calcium.

Remember if your muscles contract they release calcium causing the Kreb's cycle to increase

activity to provide energy for the muscle cells.

An important point to highlight is that succinyl CoA is a product of odd chain fatty acid metabolism,

as well as, metabolism of some amino acids.

These are alternate ways that cells can produce energy without using gluose to form pyruvate.

Succinyl Coa is acted on by succinyl CoA thiokinase to form succinate.

In the process GDP picks up a phosphate to become GTP and the CoA is released.

Succinate is acted on by succinate dehydrogenase.

In the process FAD picks up two hydrogen ions.

Just like NADH, FADH2 is one of the drivers of energy production in the electron transport

system which is the primary process of ATP production.

It is important to note that succinate dehydrogenase is the only TCA cycle enzyme that is not in

the mitochondrial matrix and is the only enzyme in the cycle that participates in the TCA

cycle and the electron transport chain.

Succinate dehydrogenase is located on the inner mitochondria membrane.

In the electron transport chain it is a part of Complex II.

Fumarate is converted to L-malate by the enzyme fumarase with the consumption of a water molecule.

Finally L-malate is converted to Oxaloacetate by malate dehydrogenase.

In the process NAD picks up two hydrogen molecules creating the third NADH of the cycle.

With oxaloacetate produced the cycle begins again.

It is important to note that this step of malate converting to oxaloacetate is a very

energy intensive step or has a positive Gibbs free energy.

This means that cell has a difficult time converting malate to oxaloacetate.

SO how does this step occur?

Well malate dehydrogenase is closely associated with citrate synthase.

Citrate synthase as we know creates the conversion of oxaloacetate to citrate.

This step actually releases energy, known as a negative gibbs free energy.

It releases so much energy that when the step of malate to oxaloacetate is coupled with

the step of turning oxaloacetate into citrate the whole process creates energy and can proceed

forward with ease.

You may have noticed that free oxygen largely has no role in the citric acid cycle, but

for some reason if a cell is in an anaerobic state the Kreb's cycle cannot proceed.

The reason is that oxygen is needed to reduce NADH and FADH2.

IF oxygen is not present we will not have these carriers available to remove hydrogen

ions.

Overall in this cycle there is no net production of any of the intermediates we talked about

but we do create 3 NADHs, One FADH2, and one GTP from each acetyl CoA then enters the Kreb's

cycle.

Remember the carbons the enter the Kreb's cycle via acetyl CoA leave as carbon dioxide

and CoA.

now this cycle has only produced one GTP so what is the point of this cycle if no significant

ATP is produced?

Well it is really a setup for the electron transport chain.

All the NADH and FADH2 produced here will produce a significant amount of ATP in the

electron transport chain, which we will talk about later.

So This is the process of the citric acid cycle otherwise known as a Kreb's cycle.

I hope you enjoyed it.

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This is Dr K and I will see you next time.