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
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.
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.. :)
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!!!
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...
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.
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.
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?
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...
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 ...
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!
Hi sir
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
you are a really clear-minded man, and you made everything so easy, thanks a lot
That was INCREDIBLE. Thank you so much.
Man you nailed it! Without a shadow of doubt you're simply the best! Keep it up!
I love your explanations, and just in time for my A&P II exam. Thank you so much!
Utterly fantastic, always have been, and still are, the best!
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.
Thank you so very much for these extremely clear and well structured explanations!!!
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.. :)
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!!!
thank you so much for the lecture, it was put in a nice simplified way that's easy to understand
Sir you are my fav biochem teacher. U make biochem amazing thank you so much
wow........!!!!!!!! l love your videos ,my life would me meaningless without them ,you have made life easier........!!!! you are truly gifted.....
You are an angel...I have a feeling that ama nail these exams, thank you sir
very soothing to learn .GREAT WORK MashaALLAH.
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!
Just in time for my final! Thank you!
Damn Andrey, back @ it again with the awesome lectures! 😆😆😆
+Musicluvr_sam And a new hair cut lol
Legend. Love you explanations.
Outstanding logically organized lectures
Thanks alot 💖💖💖
Great Lectures! Thanks!
GREAT AS ALWAYS! what textbook u use please? do u recommend such an easy books for medical study? as physiology, ect
Thank You very much! Great presentation!
Watch his vedios b4 start reading the topic and watch again after am done reading the topic then see myself perfect ...
Thank you very much, you are an awesome teacher!
thank you for saving a life
well and simply explained. thank you
awesome lectures !!!
do you have any cholesterol metabolism lecture?
amazing explanation !
beautifully explained as always
Your lectures are helping me survive biochem. Thank you!
Happy to hear that, you're welcome!
Thank you sir,, From Kenya
incredible explanation, thank u!
Thank you, Iearnt something new.
very nice sir
Great explains
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?
U r the best. Thanks a lot u help me a lot.
thank you so much as always
Great lectures man!
Thank you biochemistry LEGEND :)
Sir your lectures are awesome espicially meiosis and mitosis and genetics part, i subbed to you and im proud! keep up the good work
thanks alot you make love biochemistery 😍😍
Thank you so much.
fantastic!
Thank youuuu , u made it easy
I normally don't comment, thank you for your precious time!
formation of acetone from acetoacetate is not a spontaneous process, it uses acetoacetate decarboxylase enzyme
THANK YOU !!!♥️
So would taking an Oxaloacetate supplement (100-200mg/day) interfere with or interrupt Ketogenesis?
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?
Do they publish this chalkboard as an image somewhere so I can use as a long-term reference?
thank you sir!😃
On the bottom of the screen on the left side where it says HMG CoA releases a molecule of CoA, shouldn't it say Acetyl CoA and not just CoA?
How is step two a condensation reaction if it uses a water molecule to cleave the thioester bond?
sir, please make a video on co-relation between metabolism and catabolism ...... 😇😇
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.
You said that the pathway occurs since there is no enough oxaloacetate but why it is also used at the end?
Legend
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.)
ohk..is it ..like liver has less OAA n peripheral tissues not..so acetyl coa can enter TCA there..
Why we use ketogenesis to produce Acetyl-CoA, if the process begin with Acetyl-CoA in the first place? Thanks beforehand!
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.
Thx
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
@@eatfruitsalad345 Exactly the answer I needed and couldn't find aywhere else after watching this great video. Thanks!
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
Sylvano Anselmo
1 second ago
Has anyone studied ketogenic diet for Ornithine transcarbamylase deficiency?
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...
Did you mean Acetoacetate will increase the pH, instead of the acidity?
I feel like my MCAT is counting on you... :P
Watching AK lectures and all, I'm sure you crushed it! :P
More ketones and less sugars/carbohydrates reduces the risk of cancer.
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.
How ketone bodies is used to produce energy, because they can't used in Krebs cycle because of low concentration of oxaloacetate?
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..
taruna nagdeve me tooooo
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.
Yep...
thanksssssssssss
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?
did you find the answer to this question because i want to know the same thing
oxaloacetate is missing only in liver cells because they do gluconeogenesis, other tissues still can have oxaloacetate
wait a sec, does d3 hydroxybutarate is the same molecule as betahydroxybutarate?
You have good videos but they are not clear they are slightly blur
I don't get it. What is the purpose of turning acetyl CoA into ketone bodies, and turn back the ketone bodies into acetyl CoA?
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...
if the liver doesnt use KB's then how is he making ATP?
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.
AK LECTURES Oh! that makes more sense. Thank you for replying! I have a biochemistry exam next week and your videos are helping me out a lot!
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?
What do RBC’s use as a fuel source then?
Glucose from glycolysis
New sub :)
I love you
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 ...
Does this happen only in liver.the ketogenesis.
Yes-ketogenesis occurs only in liver
Med-students: he´s a biochemist. For him, it´s like teaching kindergarten! Now back to the books :)
But, how much weight can I lose in ONE week??????
WADA SOLYABUL
You must have so much information inside that brain of yours lol
lol my thoughts.. im like is it possible for just an hour our brain switches in exam so i can ace it XD
holla at me if you want a kidney or something