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.