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. if you did please share
this with your friends on Facebook, twitter, and google +, Like this video, comment and
subscribe. This is Dr K and I will see you next time.