This was really fantastic. I felt you read my mind when you explained why acetyl CoA is not gluconeogenic even though it "seems" like it enters the TCA cycle and makes an entire round (just like how intermediates derived from gluconeogenic amino acids can actually be gluconeogenic via oxaloacetate). So the reason acetyl CoA (and therefore fatty acids, leucine, and lysine) is not gluconeogenic is that we lose the carbons as CO2. Further, PDH is irreversible. That was awesome. A good teacher preempts her students' confusions!
Hmm, I don't think the video explains this very well. You require OAA and Acetyl-CoA to form citrate in the cycle, so if there is no net gain of OAA, then gluconeogenesis cannot occur with FFA alone.
I have been watching a few videos on the metabolism because of my pre-disposition to diabetes. I have started a Ketogenic eating lifestyle and this really starts to bring home my understanding of the ketogenic lifestyle. BTW, I've never felt healthier since I lowered my carb intake. My energy level is awesome, I immediately lost 20 lbs and the fat around my waist. Thanks for the awesome info.
I was almost about to get confused before I could find such an amazing video.....You have cleared all the misconception regarding the integration of all this cellular respiration series.
I have been struggling with the whole process of ketone production and use in Kreb's cycle but this video has helped SO MUCH! Than you very much. Great content!
Exactly my heart. I get it clearer that ketone production is to save us from using proteins for progressive gluconeogenesis; that it is vital to our system for purposes other than energy production, so that is why the body gets those F.A generating acetyl coA to be producing ketones too.
This is such a good video my goodness. This information is a must for those learning biochem and want to know the overall purpose of these starvation processes.
For anyone who has felt repulsed by the above comments, I’m sorry. There are many kind people in the world, but RU-vid is often not the place to find them. I wish you all love and happiness.
this lecture is so amazing that i had to subscribe before finishing it up. yhe voice alone made me fall in love with Biochemistry and this lecturer. let me look for your email now
Thank you for making me understand all the principles all together ! :) very well and good explained because sometimes one can get lost in so many reactions and not get the point finally but this video makes it clear all in one! :D thank you :)
It is interesting to know that in some plants and germinating seeds there does exist the glyoxylate cycle which allows for direct conversion of fatty acids to to sugars like glucose and sucrose. They managed to get around that issue of not being able to convert fatty acids to sugars, damn, nature is crafty.
Around the 8:20 mark, she says that "acetyl-coA is the product of fatty acid synthesis"...I'm assuming she meant to say that acetyl-coA is the product of fatty acid OXIDATION..right?
great explanation! but I have a question. At time 14:55 , how are cells able to use/create this atp if it is not turned in to ketone bodies first? could you please explain this part? Thanks in advance!
الاستيل co a عامل مترسب بعد عمليات الهضم المهم يساعد على هضم الدهون ال ketone bodies اللي ما تقدر بروحها (fatty acids نقصد ) تتحول لجلوكوز >> فتقوم بتحويلها pyruvate اللى بدوره ما ادري شيصيررفيه ينقلب فوق تحت ويتحول جلوكوز 😊 الحمد لله رب العالمين ترجمة عربية لمن يهمه الامر
I did a 7-day water fast last year, only drinking water with potassium/sodium salt. I learned everything within the 7 days including insulin/blood-sugar testing/oxalate/acetyl/ketone urine test.
I was having trouble understanding how fat can be used to fuel cells requiring ATP very quickly, as the breakdown of fat requires oxygen to produce ATP. Once you said that the body STORES acetyl coa in periods of long term fasting it all made sense!! the fatty acids have already been broken down in the liver and are ready to go and be transported to cells in the way of ketones! AMAZING... i am now 7 days into full ketosis and feel stronger and more energetic in the gym which is what prompted my question..
+Walid Abdo Go away bot. Your BS lies are not needed here. Any medical professional knows that long term Ketogenic diet leads to arterial calcification, the acidity from the ketones in your blood draws calcium from your bones, combine that with increased saturated fat which leads to an increase in LDL and you have created the perfect situation for you to eventually have a myocardial infarction. There are no shortcuts in health.
If you consume exogenous ketones (ex. mct oil, red raspberries, etc), in an otherwise normal (non-carb restrictive) diet, which fuel source will the brain use? Are there any genetic component or polymorphisms that would make the liver less capable of producing endogenous ketones from excess acetyl-coa? Is it widely accepted that diseases of the brain (alzheimer's, parkinson's, huntington's, etc) are likely the result of insulin resistance of the brain? And therefore ketone therapy may be helpful?
In the keto diet, you are eating a lot more protein than usual, and restricting intake of carbs (sugar/glucose) to almost 0 so that your body uses nearly-only those dietary proteins for a fuel source. I think the idea is that it's harder to take in as many calories each day on a strict keto/protein diet compared to an uncontrolled/unrestricted diet, so you should have a net loss of Calories each day, leading to weight loss. And during the times between keto meals, your body is breaking down fat (FA oxidation) for fuel (also breaks down some dietary + stored protein), leading to less adipose tissue and therefore less fat, leading to weight loss.
During fasting or untreated diabetes, in the adipose cells, TAGs are broken down into FAs + Glycerol and the constituents enter the bloodstream and travel to the liver where FAs are taken into the mitochondria matrix where they undergo beta-ox. However, in the cytosol, doesn't glycerol enter GNG to form glucose?
Beforehand, please correct me if my understanding is wrong! So, odd number of Fatty acyl chains can be converted to pyruvate(3C) to further synthesize glucose via gluconeogenesis. The main reason fatty acids canNOT be converted to pyruvate but only Acetyl-coA (or vice versa) is because fatty acids are usually even numbers and FA is synthecized/broken down in 2C units. Hope this made sense! :)
I'm just a novice on a low carb diet trying to get my head around all this. Am just wondering, once the body shifts into ketosis, why does it need to break down protein at all? Is there a reason it cannot just run on purely fatty acids & ketones alone? If the brain, etc, is able to use ketones as it's replacement glucose, while the rest of the body uses fatty acids. Then what does the body need that minimum level of glucose for?
+blk bbw In the beginning stages of fasting (before 3 days), the body breaks down protein to produce glucose (the body's main source of energy). Then after 3 days, the body starts saving protein as to maintain mechanical function of muscles. At the same time, the body goes into ketosis and produces ketones from fats as the new primary energy source for the body. The body cannot purely rely on fatty acids because it breaks down to acetyl CoA, and too much acetyl CoA creates a negative feedback that inhibits the Krebs Cycle so it can't make any energy, which is why it turns into ketones. Long-term ketosis can cause hypoglycemia and low grade acidosis. However, the benefits and repercussions of a long-term keto diet still has some debate.
Sorry but I dont understand... just say you starved yourself for 1 week but like you drink alot of water and you also just eat a little bit... when you finish starving yourself do you gain all the weight back after and also get s SLOWER metabolisim?? Please help
You will have so much energy after the first 2 to 3 days and u don't even think about food all u basically doing is cleaning out all that old stuff u had in your body for years you can go back to refeeding after or u can just do omad its especially good for people who need to loose a couple of pounds to lower their insulin levels due to diabetes
Great video on starvation! I only have 1 question to ask....in the text I have read, during starvation, intermediates for the CAC are depleted due to feeding into gluconeogensis. Without intermediates like OAA, how is the acetyl CoA converted from ketone bodies fueling the CAC? I'm not understanding this step nor have I found anything that really answers it. Thats for the help
because gluconeogeensis is located only in the liver. But ketones, that are formed also only in the liver, travel into other tissues, like the brain and there they enter the CAC, and these other tissues have enough intermediates for the CAC, because gluconeogenesis is not located in extrahepatic tissues.
This is somewhat inaccurate video. Fat stores can be converted into glucose. It is 3 carbon end of fatty acid that can no longer be processed into glucose and is converted into ketone bodies (3 carbon, just like acetone). That is why individuals who are experiencing DKA have that acetone-like breath and can sustain on fat metabolism.
So.... If ketones have the body not eat up the protein, and fats cannot be converted to glucose... Why does one loose weight from prolonged starvation?
pryuvate is not a ketone, fructose is. ketone bodies are ketones like squares are rectangles. there are 3 ketone bodies: acetone, b-hydroxybutryate, and acetoacetate. although beta hydroxybutyrate is technically not a ketone but still is a ketone body. a ketone has a carbonyl group with 2 hydrocarbons side chains. also don't get confused with keto acids. pyruvate's conjugate acid, pyruvic acid is a keto acid
~13:00 If the fasting/starving person is active would the ATP single stop the ETC Process? I am not sure of the math but what is the Calories to unit of Acetyl-coA? also it would be wonderful to have the Calories to Ketones conversion as well.
i don't understand why we needed the ketone body step. if we're backed up with acetyl-coA, why transform it into ketone bodies, only for them to be reverted to acetyl-coA again?
Because you have all these AcetylCoA's "all readied up but nowhere to go" because Krebs won't take 'em (actually Krebs can't take 'em because no electron carrier molecule is available since NADH can't unload - i.e. get oxidized - them to the ETC because excess ATP already has fedback to stop the chain.) So the AcetylCoA goes the ketogenesis route. Why? Because our dear brain can utilize them for power.
+Tony G. Reyes yes, a ketogenic diet can lead to acidosis, as all three ketone bodies are acidic and an abundance of them will overwhelm the blood's bicarbonate buffering system. This is essentially caused by the lack of diet glucose leading to a lack of insulin secretion, which promotes fatty acid release from adipose cells, which are turned into ketone bodies in the liver.
+paucceri Firstly, Acetyl Co-A can't cross the mitochondrial membrane, so unless convernted to ketone bodies it is stuck there. Secondly, in the fasting state many tissues use fatty acids for energy. Our brain can't use fatty acids for energy however, because they can't cross the blood brain barrier. However, ketone bodies (Acetoacetate and beta-hydroxybutyrate) can cross. Therefore ketone bodies provide our brain with an alternate supply of energy to glucose, which is in short supply and requires energy to make during fasting.
+paucceri I am going to breakdown your question into two parts: transport and metabolism. Transport: simply put, acetyl-CoA cannot travel through the bloodstream because it is insoluble. Ketones are water soluble and can travel through the bloodstream. Tissues and organs do need this acetyl-CoA for ATP, so ketones are sort of the packaged carrier system for acetyl-CoA to travel through the bloodstream. Metabolism: Too much acetyl-CoA inhibits its own use in the Krebs cycle. Producing ketones from acetyl-CoA reduces the amount of acetyl-CoA. With a lot more ketones (because of low ketone extraction by tissues from low insulin) and less acetyl-CoA, the Kreb Cycle is no longer inhibited. Ketones now have an easier time catabolizing into acetyl-CoA and producing ATP with the Krebs Cycle. +Kat Zibell Acetyl-CoA can cross the mitochondrial matrix as citrate through the citrate shuttle then reverting back to acetyl-CoA in the cytoplasm. However this is usually during fatty acid synthesis and the fed state. Agree with everything else you said though :)
So Acetyl Co-A could enter the Krebs Cycle as long as there is enough OAA, but in starving mode/diabetes OAA is needed to the gluconeogenesys so the excess Acetyl Co-A must go to the Ketons syntesys. Right?
I understood it that way, that in starvation mode body tries to reduce gluconeogenesis in the liver in order not to destroy our amino acids, instead, the liver produces ketone bodies, that are then transported into other tissues and there they undergo citrate cycle and in these other tissues there is enough of OAA in CC since gluconeogenesis is not located in extrahepatic tissues? But I am very unsure about this.
So she is saying if we are fasting we are using protins as a source of energy despite we have saved all exstra energy as fat. I think she missed the point of starvation which is more like constantly eating lower calories then your body need insted of fasting which boosts you metabolism.
I have been through severe starvation. About 5 and and a half weeks without food. If anyone is interested i have a detailed look at what this is like. Interestingly enough logic is not affected very much but very unfortunately emotions are very affected. Many of mt emotions were resorted to nothingness.
You had to say the brain can only use glucose for energy then you said the brain can use other fuel- ketones. Ketones can be used by the brain not only in starvation. Ketones can be used when carbohydrate in the diet is restricted. This needs to be corrected in your dialogue- to say that in the context of a diet with plenty of carbohydrates the brain uses mostly glucose for energy
But if I understand well, it's kid of impossible t avoid protein bread down as it occurs in the first couple of day of fasting? So If you fast for 2 days or 5 days you're still going to break protein, in the first two days that is. Is that a good idea if you're an athlete?
+FrostyPhoenyx thank you very much for your replay, i'm beginning to study nutrition and i really wanted know the metabolic pathway and the biochemical state in the body in persons who modify their eating behavior, changing from glucose to fats as their primary fuel source, the so famous "ketogenic diets" i'm dubious if they are really sustainable because i things they are toxic in the long run and people do not realize that.
+Tony G. Reyes no prob, good luck with your studies! yeah, I'm always kind of skeptical of these kinds of fad diets haha. I think if you want to look it up further you can look up ketosis.
From what I learned. Ketosis is benign and normal. Ketoacidosis (acidic blood pH) occurs when there are abnormal quantities of ketone bodies and is usually caused in diabetics by low insulin causing hyperglycemia (high blood sugar) and increased fat metabolism. As for sustainability, the keto diet (in nondiabetics) doesn't have long-term severe side effects except in children but you may have hypoglycemic (low blood sugar) conditions as well as low-grade acidosis. correct me if im wrong please
sorry, can anybody help me what are the diffenrences between normai acetyl coA (can do the Krebs cycle) and the 2C acetyl coA (cannot). i am confused, they are acety coA but one can and one cannot, sorry for my bad English.
I realize this was written a good while ago but: Acetyl CoA doesn't come in different forms, it's just Acetyl CoA, which has 2 carbons. However in order to enter Krebs cycle Acetyl CoA needs to react with OAA! And it can't do that if gluconeogenesis occurs, and we don't have enough amino acids that can participate as intermediates, because the cell will be depleated of its OAA because of: OAA -> PEP ->-> etc -> glucose! So Acetyl CoA + nothing can't enter the cycle.
Why We Do Need So Many People in the World At the start of the 20th century, the world population was roughly two billion people. Today, it is roughly eight billion. Of those eight billion, most are poor, and over a billion people are hungry to the point of starvation. Providing for so many people at a decent level seems too formidable a task for Earth. Moreover, each day, more bots, robots, and automatic machines are replacing human jobs. Humanity is producing enough to provide for everyone, so the question is why we need so many people. Would Earth, and humanity, not be better off if we were only four billion, for example? The truth is that we wouldn’t be better off; we would be much worse off. There is a good reason for the exponential growth in humanity’s population over the past century or so. When we look at people, we see faces and bodies, human beings, and nothing more. But the truth is much more complicated and intricate than that. Try to imagine any animal without relating it to its environment, and you will realize that it is a lost cause. The shape, color, behavior, size, longevity, and every other aspect of its existence derives from the environment where it exists. Animals are not isolated from their environment; they rely on it, follow its laws, and at the same time make up the environment that sustains them and of which they are a part. Humans, too, make up a system. We think of ourselves as isolated individuals, but we are actually parts of a global human society. We influence it, it influences us, and almost everything that is true for the animal kingdom is true for us. There are only two differences between animals and people, though they are fundamental differences. The first is that people are inherently mean and selfish, while animals are not. The second is that our desires grow and intensify, while those of animals remain largely the same. While we want more money and power the more we have of them, animals settle for what they have once they have had their fill. Worse yet, from generation to generation, we are becoming more greedy, domineering, and narcissistic. Conversely, animals’ “aspirations” do not change from generation to generation: Give them enough grass, or enough game, and they are happy campers. The reason why our desires grow while those of animals remain the same is that an increased desire makes us accelerate our development. Eventually, humans are not intended to perceive only the physical existence, but to penetrate through it and perceive the connectedness and interdependence among all of us not only intellectually, as I am explaining it here, but in the senses, just as we perceive the physical world, if not more so. Our constant desire to search, explore, discover, and learn stems from our aspiration to know the deepest levels of reality. That knowledge is the sole prerogative of humans since only people develop such profound desires. As our desires grow, we must learn to direct them toward discovering the purpose and structure of life. New desires first appear on the crassest level, and we must cultivate them, raise them to the level where they enhance our perception of reality. Because these desires are so intense, we need more people to “share the load.” As just said, although we feel isolated, we are in fact one system. Everything we think is ours is actually part of the system of humanity and all of humanity shares it. Therefore, our desires are also not personal, even though they feel as such. Every time we elevate one desire from the corporeal level to the higher levels of perception, we influence all of humanity. And every time a person dies, the burden of elevating our common desire grows heavier on all of us. This is why the life of every person is precious. It determines the pace of advancement of all of humanity. If we realized how deeply we are connected, and what harm we cause by mistreating other people, if we felt it as it really is-that we are torturing ourselves-we would not dare mistreat each other or leave one person uncared for.
I see your thought process, but no, The body will use excess amino acids to fuel gluconeogenesis before breaking down muscle. So more fat will be broken down but the ability to synthesise new protei ns and build muscle is not as great until you ingest a high protein meal to replenish amino acid stores
Great Video! Just have one question: are amino acids from protein breakdown the primary source for gluconeogensis during the initial phase of starvation (prior to the switch to using ketone bodies as fuel)? And what role does lactate from red blood cell glycolysis or glycerol from triacylglycerol breakdown play in gluconeogenesis during this phase? Anyone read up on this?