Citric Acid Cycle (Kreb's Cycle) Made Easy

[@alanabanana3145]

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.

[@quinoarocks]

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

[@samuelgreenrod1812]

I've seen the enzyme referred to as both. After all, a CO2 is produced, so arguably to is a decarboxylase. It is easier when referred to as a dehydrogenase because it relates it to the a-ketoglutarate dehydrogenase which does pretty much the same thing.

[@ericrojo9873]

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.

[@UTHSCSA-hb1vn]

+Eric Rojo Pyruvate Dehydrogenase is a multi-enzyme complex that yields the Acetyl-CoA required by the Kreb's Cycle. The first enzyme in that complex is called Pyruvate Decarboxylase. He probably meant to reference the complex as a whole, rather than simply one of its parts.

[@ericrojo9873]

+UTHSCSA 2019 Pyruvate Dehydrogenase and Pyruvate decarboxylase are both multi-unit complexes which act on pyruvate. They both utilize thiamine pyrophosphate to cleave off CO2 as their first steps. However, they are different enzymes/complexes. If there are any discrepancies between the nomenclature in the texts we are using there may be some confusion on either one of our sides. Cheers!

[@Resynchronise]

The pyruvate decarboxylation is done by the pyruvate *dehydrogenase* complex!

[@CastilloTallaj]

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.

[@CastilloTallaj]

Carboxilase

[@spideylover4105]

Yup

[@Goldlinx]

Deer. Dosha. You. Are. A. Good. Job.

[@shrishtibhattarai8319]

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

[@angelalopez6667]

Omg you have saved my life. Amazing explanation! Thank you so much!!!

[@DirtyMedicine]

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

[@Krissyface1234]

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

[@KateTolhurst]

This just sounds like a load of letters being said really quickly

[@JoliBastin]

Going a bit too fast to keep up with to be honest.

[@frenchfries2378]

very fast, not simple or step by step at all. ):

[@deltawolf]

Kris Dee The beauty of a video is that you can pause and replay it as many times as you want. I think this is a good one. Speaks clearly and a good microphone in contrary to other videos i've seen on youtube.

[@massive223]

take notes and skip backwards every so many seconds until you've got everything noted down, by the end of this video you can have a very nice step by step on paper and will most likely have a good understanding of whats going on after hearing it so many times.

[@noaamaallana8263]

slow it down, its a great video, you can change the speed and as both Hoomes and massive223 said there are other ways to ensure its going at your speed

[@jessemerriman460]

7:03 which free oxygen are you referencing? Also, it's needed for reduction...or oxidation? Thanks.

[@Marzbarz3]

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 :D

[@SirHadoken]

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.

[@MrPridizzle]

Oooh yaah doen't say aye hozer? Respecting the Canadian accent! Thanks for the video!

[@Blooomer]

hey buddy this ain't making learning simple u r so fast

[@kittycat1768]

Your glycolysis video was much more comprehensible... just saying

[@dennisliew4473]

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?

[@jaymefrear9403]

Thank you!!! Please make more videos!! They have helped me out SO much today!!! :D

[@ericdzenis2786]

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.

[@Krissyface1234]

yeah i feel like maybe he gets it mixed up because of FADH2

[@ludovicaisabellaricci8173]

Thank you from Italy Doc :)

[@abbydovis8250]

More metabolism videos pleaaaaaase. you are really clear.

[@rdareyes]

Thank you for this! More videos on other pathways too please?

[@iMedSchool]

Discussion of the Citric Acid Cycle

[@4ndr3z4omm]

great presentation Dr. !!

[@aaronramirez4068]

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

[@bsilano]

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!

[@dianaarnold7019]

How are you now, after 9 years? If you have chronic health issues, chances are that this is the how-to primer and explanation that you're looking for. I worked as an RN in multiple teaching hospitals. I also vetted docs treatment of patients for the WHO and was a code team member. kzbin.info/www/bejne/hJWcdYSOrteCoqcsi=dxYPXy46Ec4aOMc1

[@kikkirow]

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.

[@faffaf4004]

thank you so much

[@samuelgreenrod1812]

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.

[@jessaemmyloucarmelbismar8347]

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?

[@bilaljudeh8862]

i lost you at 0:40 lol

[@bluerose6221]

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.

[@warkinatujuba3289]

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

[@Aleen166]

Very informative. Straight to the point and easy to digest. Thank you!

[@SuzyVA]

You lost me after a minute. Sorry. Too much, too fast.

[@noaamaallana8263]

slow it down, its a great video, you can change the speed and you can rewind, repeat and pause

[@gnanamaheswar8403]

very clear.. i like it

[@rashidaissa7139]

Would you happen to have a video on gluconeogenesis?

[@thutruongnguyen185]

Thank you!

[@AnaIsmeSara]

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!

[@ellipszia]

I love you dude for doing this :D

[@ProfYounge]

Thank you.

[@drdoor9668]

thanks for the awesome explaining ......keep its up (:

[@peterchindavong]

Just a small note, the first structure you showed was not pyruvate, that was pyruvic acid.

[@adagbapsamuel7743]

Downloaded for personal use

[@vydehi17]

excellent ,excellent ,excellent oxygen is needed to oxidize NADH2 and FADH2

[@hashikashaman1192]

Why step 4 is more exergonic compared to step 3 in the Citric acid circle?

[@ellisguernsey4892]

Amazing

[@thekerns2009texas]

awesome!

[@anneaxline]

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

[@juliolazaro28]

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

[@kneetoground]

Great video, but can you speak slower like you did in your glycolysis video?

[@samanthagonah8243]

The link to the iphone app aint working

[@gretavaladez419]

urea cycle please!

[@mailaernesto]

Great video, but can you speak slower like you did in your glycolysis video?

[@rocketrmt]

You can make the video speed slower in the video tab.

[@burtonjr1]

I honestly can't stand the way this guy speaks. On to the next video!

[@jonathanaugustin647]

Define : Made easy

[@lindakaka1754]

Awwww. You just showing of

[@Person46883]

This is good for study if you already know the material... Otherwise I wouldn't recommend. Haha

[@popcornvixen123]

Electron Transport Chain.... and and more

[@anyothetre]

toooooo fasssssstt!!!

[@atteindresiempredad]

I think it s pyruvate dehydrogenase and not carboxylase

[@robpaprox]

BIO 1000... about as 'easy' as it gets

[@kittycat1768]

Introductory high school biology here... this and frickin' Fick's First Law of Diffusion

[@Stealthycybertaco]

dont understand =(

[@Shivani-ki5wl]

I don't understand all words you say, it would be easier to follow along if you also wrote down all the difficult chemical terms you're pronouncing.

[@ifrahabdihussein6610]

Took fast

[@badtoad6865]

Why would a person take citric acid 1000 mg a day

[@michellen2973]

ETC! ETC! ETC!

[@mathewllanes6018]

hahaha

[@alexfung7349]

Talks way too fast

[@davewhiteatpsynthase]

+Alex Fung Just listen slower.........

[@SirHadoken]

+Dave White I'm not sure if it works that way..

[@noaamaallana8263]

i think he means the video speed :P

[@drtreg]

Word salad.

[@babyyoda4294]

talking way too fast.