I'm a Biochemist, with a phD in Microbiology, and I think your lectures are a great great initiative, they inspire me to do something similar here in Brazil! Congrats!
Legend! what are the chances that you came back to make more videos on a topic that I have a test on in one week. Absolute savior and legend. Once I graduate and get a job with my degree, i'm donating fat stacks your way. Saved me too many times to count! Thanks for your dedication and generously giving us these lectures for free!
I've been looking at videos for 10 mins trying to understand this pathway, and then yours explains everything I was looking for within the first 3 mins. Thank you for all your great lectures
Even after a very long time, I still from time to time go and watch your videos. Excellent, clear, and on point as always. Amazing work, man. Really amazing
OMG simply cant thank you enough!!! absolute saviour (aklecture saved my yet again after physiology!). Currently having biochemistry lectures which I understand nothing about (why cant my lectures be like this~sigh~). Thank you again!!!
I have a little issue with the last part, you said that both acetoacetate and D3 hydroxibutirate are transformed back into Acetyl Coa and combined with oxaloacetate to produce ATP molecules BUT, you just said that oxaloacetate is almost depleted because starvation... so what oxaloacetate are you using there to obtain ATP molecules anyway?
El Vegano Cordobes oxaloacetate is depleted in the Liver since it is utilised for gluconeogenesis (and gluconeogenesis exclusively takes place In the Liver)... the peripheral tissues might still have the required amount of OAA for tca cycle to operate.. :)
I can't really understand WHY people can't explain the ketogenesis like you did. Our books have been written to confuse ourselves, so, with all my heart: THANK YOU.
Hey Andrey, just a note! The step in which occurs the transformation of Acetoacetate to Acetone can be catalyzed by an enzyme called acetoacetate decarboxylase, but it can be spontaneous as you said. Keep up the great work!
shouldn't also the decrease in oxaloacete in the mitochondria slow down the rate of gluconeogenesis and as a result cause the body to increase glycolysis as compensation, leading to low levels of glucose and high levels of acetyl-CoA -> increase in ketone bodies -> ketoacidosis? But since high levels of acetyl-CoA inhibit pyruvate dehydrogenase, pyruvate will accumulate as a result leading to a decrease in blood pH as well (lactate & alanine production), correct?
Can we say, (simplifyng to the utmost) that Acetyl-CoA is "transferred" from the liver to extrahepatic cells where it can be used, while it can't be used in the liver, due to the lack of OAA?
Very rich content here. It took me 2 sessions to finish watching. But, by the time I watched the 2nd and 3rd ketone bodies, I forgot how we started with the high level of the fuel source acetyl-CoA to start with. Maybe I need to watch this 4 times.
So the reduction of acetoacetate into beta-hydroxybutyrate, and then subsequent reformation into Acetoacetyl CoA, causes acetoacetate depletion (as well as lower insulin), and thus allows for lipolysis to occur in adipose tissue? (I am speaking of nutritional ketosis, not ketoacidosis.)
This I think is dependent on how much OxaloAcetAte you have to begin with. Toward the beginning of the vid he mentioned that you need OAA and Ac-CoA to begin the CAC, but if you have LOW levels of OAA and HIGH levels of Ac-CoA. Hence the Ketone Body pathway commences. My theory of why we end with Ac-CoA also is if we imagine there was a pathway that DID NOT result in Ac-CoA production? The amount of Ac-CoA in the liver, or tissues, or blood, etc...would run out VERY quickly since we'd be exhausting the Ac-CoA stores in this pathway, while we have less production of Ac-CoA's to begin with. We'd run out of energy much faster
This is more like a process used to store up the excess acetyl-CoA rather than producing it. There's an extra amount of acetyl-CoA and not enough OAA to use it up, so the extra acetyl-CoA is directed for storage, to be used later.
I dont understand how non-hepatic cells still have oxaloacetate (OAA) in a fasted state but the liver doesn't? If I'm fasting for several weeks, shouldn't the non-hepatic cells also be depleted of OAA? Where is this OAA coming from?
maybe 1 year too late (but just for other ppl looking thru comments i guess) OAA is only depleted in the hepatic cells because gluconeogenesis (OAA -> glucose) only takes place in the liver. In non-hepatic cells OAA participates in the TCA cycle without being used up
Sir, your forehead shines and I really like that... It will shine more if you put mustard oil on your forehead... And I will love to watch your videos always... Thank you
For some reason, you are talking about ketoacidosis and ketosis as one. But they are different. When we're fasting, it is NOT the same as if we were diabetics...
2 years later, but maybe for someone else: ketone bodies are exported from liver to other tissues where there is plenty of oxaloacetate because gluconeogenesis does not occur there so citric acid cycle can run there
extender01 why can’t muscles use free fatty acids to produce energy via beta oxidation then? FFA cannot pass through the blood-brain barrier to get to the brain cells hence their need of ketone bodies. But beta oxidation can happen in Muscle and cardiac cells so why doesn’t this happens instead?
I didn't get one thing ..if OAA is less....n ultimately ketone bodies have to be converted to acetyl coA then what's the need of ketogenesis??? ...either way acetyl coA is formed which has to enter TCA.. where OAA is less..
The OAA is only depleted inside of the Liver though, so all of your other cells in the periphery still have OAA. Ketones are better because they don't require Insulin...Insulin inhibits important enzymes/pathways like hormone sensitive lipase.. So when Insulin is around you cna't break down fat and utilize it for energy, you can only expend the consumed carbs, or they will get turned into fat. So when you need energy and don't consume carbs you're just going to take that newly formed fat from the previous carbs that were turned into fat and then you'll just re-break them back down through the beta-oxidation pathway.
I have a question. Does Acetyl CoA go to Ketogenesis because of low OAA levels or because body wants to save aminoacids and does not want to use proteins for krebs cycle.??
When the body has no free carbohydrates available, fat must be broken down into acetyl-CoA in order to get energy. Acetyl-CoA is not being recycled through the citric acid cycle because the citric acid cycle intermediates (mainly oxaloacetate) have been depleted to feed the gluconeogenesis pathway, and the resulting accumulation of acetyl-CoA activates ketogenesis. And body saves amino acids which are used for gluconeogenesis under strvation condition.
If the ketone bodies become acetyl-coA again, then how does that solve the issue of not enough oxaloacetate and too much acetyl-coA during a fasting state?
So basically Ketogenesis occurs because we have an accumulation of Acetyl-CoA and it cannot enter the Krebs cycle because there is not enough oxaloacetate around (since it is being used by the liver). What i dont get it why the ketones come back in the cell to produce even more Acetyl-CoA.. It won't resolve anything because we still dont have enough oxaloacetate right?
+LostHeaveN14 You're thinking about the acetyl CoA coming back to the liver, but thats not the case. The ketone bodies go to peripheral cells such heart cells and brain cells. These cells typically have enough oxaloacetate because they get it from glucose breakdown. So they can easily use the ketone bodies to help generate acetyl CoA, which is in turn used to generate ATP.
u said in the above comment; "These cells typically have enough oxaloacetate because they get it from glucose breakdown" but in this state, body cells dont have glucose 4 degradation. thats why the liver do the gluconeogenesis pathway, to provide peripheral cells with glucose can u please make it more sense to me?
sir your writting is too small.. I am facing a lots of problem in noting them dowm in my copy. some words are roo small that its hard to identify. or better read once whatever you write ...
oh my god, i wish i knew what all this shit was. you need like colors or like shapes for me... all the words are confusing the heck out of me man... your SMAAAARTTT i LOVE ITTTTTT!!! hahahahah i really love that al of this is back up with chemistry and biology...
