Medical School – Citric Acid Cycle (Kreb’s Cycle) Made Easy


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.

71 thoughts on “Medical School – Citric Acid Cycle (Kreb’s Cycle) Made Easy

  1. During the eighth step of kreb cycle, which mean succinate is oxidised into fumarate by succinate dehydrogenase in the presence of FADH2 as cofactor. I have 2 problems.
    1. Why does FAD+ is used instead of NAD+?
    2.How FADH2 moves out of the enzyme succinate dehydrogenase as FAD+ is a prosthetic group that is tightly bounded to the succinate dehydrogenase?

  2. Thank you for making this video. I have one concern, which is that in the PDH complex mechanism, it's not NADH2 that's produced but NADH.

  3. i read in stoker's book that the enzyme succinyl CoA SYNTHETASE removes the coenzymeA by a thioester bond cleavege. and im surprised that it is not the SYNTHETASE is used but rather the THIOKINASE.. are they the same? 

  4. I don't know if I should trust the credibility of this video. It has a fatal error at 0:11.
    Only a complete stumbling fool would think that the citric acid cycle is the "Kreb's" cycle. It is the "Krebs" cycle. Kreb didn't do the science. Krebs did the science.
    Don't be an idiot.

  5. I'm sorry to tell you man but the first enzyme listed is mistaken the enzyme you are looking for is pyruvate dehydrogenase complex that converts pyruvate to acetyl coa…. The one you listed ( acetyl coa decarboxilase ) transforms pyruvate into oxaloacetate which is going to be converted to pep and then to piruvate one more time.

  6. You need to be a prodigy or a graduate of MIT to understand this! I'm just trying to be and stay healthy. I like your video but, just wish I was as smart as you!  I'll keep searching!

  7. Too fast to even comprehend any of the steps. Think about the people who aren't phD's in biochem. You should do an in depth video on the mechanisms of this cycle. 

  8. made easy! lol, bro I didn't understand 3/4 of the vocabulary. and I watched 2 other types of books that were comprehendible.

  9. I stayed on this channel after viewing the Glycolysis made easy, but this one is just not as good. I realize you're trying to keep videos under a certain amount of time, but maybe having a Part I and a Part II would have been better. Thanks anyway

  10. If the speed is the problem you can change it in the video settings to 0.5. It just slows down the talking but it might help 😀

  11. the glycolysis video was shorter than this with less steps. this video is 3 minutes faster with 3x the amount of steps. whaaaaaaaaaat happened. 🙁

  12. I'm pretty sure (looking at text right now) Entering the Krebs cycle Pyruvate Dehydrogenase (not decarboxylase) is used to yield Acetyl-CoA, CO2 and FADH2 which is then converted into NADH. Pyruvate decarboxylase is utilized in fermenation of pyruvate to acetaldehyde.

  13. Warning: On the video it has "Pyruvate Decarboxylase Complex" to convert Pyruvate to Acetyl CoA. This is incorrect. It is "Pyruvate Dehydrogenase Complex" that converts pyruvate to acetyl CoA

  14. Ok, I follow you, yeah, u…wait..what? Wait, no, I need to s..Agh! Why are y- what, no don't go .. Ugh, I'll just rewind it.

  15. I think it should be NADH, not NADH2. There are 2 high energy electrons (negative charge) involved with NAD+/H+ forming NADH (no charge). This second hydrogen does not appear in any textbook I have read.

  16. Just curious as to how NADH2 has two hydrogen molecules and not one?

    Formula showes number of hydrogens going from four as Pyruvate molecule and three as a Acetyl Co-enzyme A. Which makes sense if NAD+ went to NADH not NADH2?

    May have missed something along the way but please let me know, been killing me.
    Thank you

  17. O2 is the final acceptor of the ETC, which requires NADH and FADH2 (which can be thought of as precursors of Vitamins B2 and B3). Therefore, without the enzymes within the TCA Cycle, not only will you have the clinical manifestations of B2/B3 deficiency, but you will be unable to utilize O2's role as a substrate by which to generate ATP. See my channel for a USMLE mnemonic video explaining the link b/w TCA Cycle & Vitamin utilization

  18. This was super helpful!! I don't know why but i always find it difficult to link these processes to ETC and this video helped me with it a lot

  19. The kreb cycle takes place in the mitochondrial matrix. At the end of glycolysis, pyruvate is converted by pyruvate decarboxylase complex to acetyl-CoA.

    Acetyl-CoA combines with oxaloacetate by the enzyme: citrate synthase to produce citrate.
    Oxaloacetate can be converted into one of the 20 amino acids or aspartic acid by transamination
    Kreb cycle regulation citrate synthase is activated by a GDP(ADP) and inhibited by a GTP (ATP). NADH, and succinyl-CoA.
    The citrate produced inhibits phosphofructokinase, the enzyme that facilitates a rate limiting step of glycolysis. The body doesn’t want to create too much ATP if it doesn’t need it. Too much citrate creates a negative feedback on the glycolysis pathway to precent energy production.

    Citrate isomerizes to cis-aconitate and eventually to iso-citrate by the enzyme Aconitase.

    Isocitrate is acted on isocitrate dehydrogenase to form oxalosuccinate. Dehydrogenase enzymes always involve the removal of hydrogens. During this step, NAD picks up 2 H atoms. This is an irreversible step. This is one of the rate limiting steps of TCA and produces the first CO2. The production of NADH is important because the loading of these energy carriers will drive the energy production in the electron transport chain.

    Oxalosuccinate is acted on by isocitrate dehydrogenase to form alpha-ketoglutarate (another TCA intermediate that can be converted into an amino acid and transaminated into glutamate). One molecule of CO2 is produced. Any intermediate that can turn into an amino acid, can be created from that amino acid. The amino acid Glutamate can be broken down by glutamate dehydrogenase into alpha-ketoglutarate and enter the TCA cycle.

    Alpha-ketoglutarate is converted by alpha ketoglutarate dehydrogenase complex into succinyl-CoA. In this process, CoA is added and produces the second Co2 molecule and a NADH and H+. Cofactors like thiamine, pyrophosphate, CoA are req’d for this step to take place. The complex is inhibited by ATP, GTP, NADH, and succinyl CoA. It is activated by calcium, if your muscles contract, they release Ca which cause the Kreb cycle to increase activity to provide enough energy for the muscles cells

    Succinyl CoA is a product of odd chain Fatty acid metabolism and metabolism of some amino acids. This allows cells to create energy without using glucose to form pyruvate.

    Succinyl CoA is converted to succinate by succinyl CoA thiokinase. GDP picks up phosphate to become GTP, and CoA is released.

    Succinate is acted upon by Succinate dehydrogenase to from fumarate. In the process, FAD picks up 2 H ions to produce fumarate. FADH2 is one of the drivers of energy production in ETC for ATP production

    Succinate dehydrogenase is the only TCA enzyme that is not in the mitochondrial matrix. It is the only enzyme that participates in the ETC, it is located on the inner mitochondrial membrane and is part of complex II.

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

    L-malate is converted to oxaloacetate by malate dehydrogenase. In the process, NAD picks up 2 H atoms creating a 3rd NADH of the cycle.

    This step is a very energy intensive step, + gibbs free energy, this means that the cell has a difficult time converting malate into oxaloacetate.

  20. the summary in this video is great, but it is too fast. I just change the speed settings on this video to .75 and its a lot easier to follow!

  21. This is a good video but I think it would've been better if you'd explained what happens to each molecule during the process. For example just saying NADH is produced doesn't really mean much. If you explained that the oxidation of OH to a ketone group led to the reduction of NAD+, it might be a bit easier.

  22. Thank you so much especially for the extra notes on the regulation of different enzymes and products being formed.

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