Test Of Understanding - Energy Metabolism For A Dummy

[yerrag]

I'm going to admit, this subject still confuses me and in these discussions I get the feeling I'm not on rock solid ground in terms of understanding. It is complex to go down to the nuts and bolts of it and I end up simply lost as I read deeper into it. I end up simply skimming the article and just going past it towards the summary. Because of this, I feel like I've not mastered grade school before going to high school when it comes to this. So I'm going to just explain my understanding of it and if you see anything wrong, please correct me.

1. Oxidative metabolism is the most efficient way of producing energy for humans. It involves the use of oxygen and glucose to produce energy, with carbon dioxide as one of the by-products. It is also called by another names, which at this moment eludes me. The mitochondria of the cell is where this takes place.

2. Aerobic glycolysis is a less efficient way of producing energy. Oxygen and glucose is also involved, but for some reason, there is xomething missing that keeps oxidative metabolism from being the energy production pathway. What is the reason? Is a by-product here lactic acid or carbon dioxide?

3. Anaerobic glycolysis uses glucose but no oxygen. This happens when there is a lack of oxygen, and the body resorts to this pathway. It involves fermentation and lactic acid is a by-product.

4. When the body is low on sugar, adrenaline and glucagon signals the liver to convert glycogen to glucose. When there is enough glycogen, does adrenaline cause cortisol also be produced?

5. When the blood sugar is low (hypoglycemia), the adrenal gland produces the hormone cortisol, and this converts protein, using certain amino acids in the protein to make glucose, in a process called gluconeogenesis.
There are also other amino acids in protein which can be converted into fat, what happens to this fat? Is it stored or is it metabolized?

6. How is fat metabolized? Does it get converted also to glucose and metabolized? Or is fat metabolized as fat? What is the difference, energy-wise and by-product-wise, when fat is metabolized?

7. What is the difference between saturated fat being metabolized and PUFAs being metabolized?

8. What is the difference between short & medium chain fatty acid metabolism and long chain fatty acid metabolism?

9. Why does coconut oil bypass the liver and gets metabolized directly by cells, if that is true at all? Is it because it is a saturated oil? Or is because it is saturated and has short and medium chain fatty acids? Does the oil from butter bypass the liver as well? What about PUFAs that are short and medium chained, will it bypass the liver?

I admit to getting lost when the discussion turns into equations of acetyl-CoA, pyruvates, acetyl acetates. The chain of reactions involved needs me to microdose on LSD to fully understand it (I hope?). If you could explain in dummy terms, that would be great.

And I've tried doing some research. It just doesn't stick. Or maybe I never got to hit the bulls-eye. But in the discussions on cancer, and whether sugar helps the healing more than it helps the cancer, without understanding this well enough, it's very hard to sift through the confusion.

Hope someone can clear this up for me, and certainly I hope there is a unified thought on this between mainstream science and alternative science. Or will there still be major points of disagreement. It doesn't appear to be so, and probably the best test is if all Wikipedia entries on energy metabolism find agreement in this forum.

 

[Mito]

Chris Masterjohn is doing a video series on energy metabolism. Here is the first one
in the series of 21 videos so far. Heavy into the biochemistry but it will answer most or all of the questions you have listed if you're willing to spend the time to watch (and rewatch) them.

 

[walker_in_aus]

Chris Masterjohn is doing a video series on energy metabolism. Here is the first one
in the series of 21 videos so far. Heavy into the biochemistry but it will answer most or all of the questions you have listed if you're willing to spend the time to watch (and rewatch) them.

THANKS this is awesome.

 

[yerrag]

Thanks mito. This will be a fun movie weekend

 

[yerrag]

I went through the first three of the series. On the third ones, the explanation of cellular respiration is framed in terms of membranes and pumps. Given that Ray Peat subscribes to the active transport mechanism, would the explanation below differ from how Gilbert Ling, Gerald Pollack, and Ray Peat would see it in terms of end result? I mean, if we're to see the process as a black box, would the inputs and outputs of cellular respiration be the same regardless of whether an active transport system or a membrane-pump system is used to describe it?

 

[Travis]

1. Oxidative metabolism is the most efficient way of producing energy for humans. It involves the use of oxygen and glucose to produce energy, with carbon dioxide as one of the by-products. It is also called by another names, which at this moment eludes me.

It's sometimes called respiration.

2. Aerobic glycolysis is a less efficient way of producing energy. Oxygen and glucose is also involved, but for some reason, there is xomething missing that keeps oxidative metabolism from being the energy production pathway. What is the reason? Is a by-product here lactic acid or carbon dioxide?

A disabled electron transport chain does this. There can be many causes. For example: errors placed in the DNA encoding for cytochrome c oxidase has been shown to produce these Warburg Effect-like changes. Cytochrome c oxidase, sometimes abbreviated as COX, is integral to oxidative metabolism. It forms the very last last stage as O₂ attaches to its heme iron. Electrons from the heme ring and iron are transferred to oxygen which can then take up H⁺ forming water.
The Citric Acid Cycle stores electrons that it pulls off of pyruvate/acetyl-CoA by placing them on NAD⁺ as hydride [:H⁻] ions. This is a hydrogen with two electrons. These electrons are fed into the electron transport chain and the proton (H⁺) is used to turn ADP and phosphate into ATP and to form H₂O from O₂.

ADP + HPO₄²⁻ + H⁺ ⟹ ATP + H₂O

O₂ + 4e⁻ + 4H⁺ ⟹ 2H₂O

4. When the body is low on sugar, adrenaline and glucagon signals the liver to convert glycogen to glucose. When there is enough glycogen, does adrenaline cause cortisol also be produced?

@Diokine is into glucocorticoids. I bet he knows.

6. How is fat metabolized? Does it get converted also to glucose and metabolized? Or is fat metabolized as fat? What is the difference, energy-wise and by-product-wise, when fat is metabolized?

A little of both. On a low-sugar diet, more fat will likely be turned into glucose. But on a 40/40/20 diet, I think most fats would be metabolized using β-oxidation. This is a neat process, and it forms acetyl-CoA directly which can be used in the Citric Acid Cycle and there is no pyruvate required. When reading about β-oxidation, make sure not to confuse the terms "acyl-CoA" and "acetyl-CoA".

7. What is the difference between saturated fat being metabolized and PUFAs being metabolized?

The absorbtion kinetics are different. At the same chain length, saturated fats are more likely to go to the liver (portal vein). Unsaturated fatty acids are more likely to become phospholipids in the intestines and sent through the lymph. This is partly why a PUFA diet lowers serum cholesterol: the unsaturated fatty acids form chylomicrons and bypass the liver where much cholesterol is synthesized. Cholesterol tends to be packed in higher concentrations in lipoproteins from the liver..

8. What is the difference between short & medium chain fatty acid metabolism and long chain fatty acid metabolism?

The velocity for one. Using radiolabeled fatty acids, chemists have measured that for each two carbon increment in length, the speed of metabolism is reduced ~100× (by measuring the radioactive CO₂ emitted). Longer chains need carnitine transport to get inside of a cell; shorter chains do not. Also, very long chains are metabolized by peroxisomes, a special organelle in some cells that use hydrogen peroxide to degrade fats.

9. Why does coconut oil bypass the liver and gets metabolized directly by cells, if that is true at all? Is it because it is a saturated oil? Or is because it is saturated and has short and medium chain fatty acids? Does the oil from butter bypass the liver as well? What about PUFAs that are short and medium chained, will it bypass the liver?

I'm pretty sure that most bypass the liver to some degree. I think it's helpful to look at the relative amount that goes to the liver vs the amount that goes to the lymph. As medium-chain saturated fatty acids, the majority of coconut oil should go to the liver. I don't think this is necessarily a bad thing.

 

[yerrag]

Thanks Travis for the answers.

I wonder if you agree with the video. In it, Chris talks about respiratory compensation. He says that high carbon dioxide in the blood causes the breathing rate to increase. The increased breathing rate is meant to increase the rate at which carbon dioxide is expelled to correct for the low blood pH condition that comes with increased carbon dioxide. Based on this reasoning, he says that patients on ventilators would do well to be fed lo-carb hi-fat diets because the reduced carbon dioxide production of fat metabolism would enable them to breath at a lower rate, as there is less carbon dioxide to expel. But would the lower breathing rate of the hi-fat diet be a result of a lower metabolism rate?

 

[DuggaDugga]

I second @Mito on Chris Masterjohn's energy metabolism series. He also has a podcast called "Mastering Nutrition" that's a bit more accessible. Highly recommend all his work.

I'm no expert, but I'll take a swag at your questions:

1. Oxidative metabolism is the most efficient way of producing energy for humans. It involves the use of oxygen and glucose to produce energy, with carbon dioxide as one of the by-products. It is also called by another names, which at this moment eludes me. The mitochondria of the cell is where this takes place.

Glucose and fatty acids both get metabolized to acetyl-CoA, which enters the mitochondria for oxidative phosphorylation. Oxidative metabolism isn't just a glucose thing, but there are profound differences along the way that make glucose preferable.
Acetyls are just a methyl group and a carbonyl, which are bound to CoEnzyme A.

, which are bound to CoEnzyme A to create acetyl-CoA:

Since fatty acids contain more carbons per gram that glucose, some people make that argument that that makes them the preferable energy substrate. This is a reductionist view of metabolism, but let's compare glucose to palmitic acid:

On top is glucose, with formula C6H12O6
On bottom is palmitic acid, with formula C16H32,O2
Notice how glucose has an oxygen for every two hydrogens (H2O); carbohydrate. Palmitic acid? Not even close; an oxygen for every sixteen hydrogens. Glucose has the same number of oxygen molecules as carbons, so it needs another for each CO2 produced; palmitic acid needs much more than that.

So a natural next step is to understand how those two energy substrates make it into acetyl-CoA; what are the notable differences and their implications.

• Glycolysis, in a series of steps, converts glucose to two pyruvate. The pyruvate dehydrogenase complex (PDC) then converts pryuvate to acetyl-CoA, with a molecule of CO2 a by-product. Or, pyruvate carboxylase (PC) can convert pyruvate to oxaloacetate, a rate-limiting intermediate that condenses with acetyl-CoA to produce citrate in the citric acid cycle (AKA the Kreb's cycle, AKA the TCA cycle). For this reason, "fats burn in the flame of carbohydrates".
  
• The process of beta-oxidation requires different enzymes based on the saturation of the fatty-acid and whether it has an odd or even number of carbons. I haven't gotten into the weeds on beta-oxidation, but the stereochemistry of PUFA require additional enzymes, which I suspect is why the cell preferentially stores PUFA while burning saturated fats. Either way, it doesn't produce the additional CO2 that the PDC does.

There is of course far more detail involved, but some marked differences can be elucidated with a little research.

2. Aerobic glycolysis is a less efficient way of producing energy. Oxygen and glucose is also involved, but for some reason, there is xomething missing that keeps oxidative metabolism from being the energy production pathway. What is the reason? Is a by-product here lactic acid or carbon dioxide?

To add to @Travis 's response. Oxidative metabolism may not be utilized under circumstances where oxygen can't be utilized. As Travis pointed out, this could be due to dysfunctional mitochondria, by oxidative damage, DNA methylation, various deficiencies. Another common circumstance is under hyperventilation due to extreme exercise or some other stress (imagine hyperventilation, inability to breath). To survive the stress (real or perceived), the body creates fast, inefficient energy without oxygen through the process of fermentation. Lactic acid is indeed a by-product, and the liver is responsible or converting it back to glucose a la the Cori cycle.

3. Anaerobic glycolysis uses glucose but no oxygen. This happens when there is a lack of oxygen, and the body resorts to this pathway. It involves fermentation and lactic acid is a by-product.

True

4. When the body is low on sugar, adrenaline and glucagon signals the liver to convert glycogen to glucose. When there is enough glycogen, does adrenaline cause cortisol also be produced?

I think most of us under stress will exhaust our glycogen stores fairly quick.

5. When the blood sugar is low (hypoglycemia), the adrenal gland produces the hormone cortisol, and this converts protein, using certain amino acids in the protein to make glucose, in a process called gluconeogenesis.
There are also other amino acids in protein which can be converted into fat, what happens to this fat? Is it stored or is it metabolized?

Regarding your last question: I think the metabolism/store of fatty acids under the influence of glucocorticoids is complex. Same with glucocorticoids and insulin sensitivity. Adipose tissue, under the influence of cortisol, uptakes glucose and releases fatty acids, while skeletal muscle becomes insulin resistant to spare glucose for other organs like the brain. The type and depot of adipose seems to be greatly influenced by cortisol-- not for the better.
Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity

6. How is fat metabolized? Does it get converted also to glucose and metabolized? Or is fat metabolized as fat? What is the difference, energy-wise and by-product-wise, when fat is metabolized?

Beta-oxidation mainly. Storage as a triglyceride requires a glycerol backbone. Triglycerides can be saturated and unsaturated; the latter is therefore more vulnerable to oxidation. It also means when they're metabolized and released, they create oxidative stress as Peat has pointed out many times. The glycerol backbone can be utilized in gluconeogensis.

7. What is the difference between saturated fat being metabolized and PUFAs being metabolized?
Different enzymes are required for PUFA because of cis- bonds. Unsaturated fats are susceptible to oxidation, particularly when a double bond exists on both sides of a carbon. The free radicals produced are dependent on the length carbon chain and the placement of the double bonds.

8. What is the difference between short & medium chain fatty acid metabolism and long chain fatty acid metabolism?
Shorter molecules tend to be more reactive.

9. Why does coconut oil bypass the liver and gets metabolized directly by cells, if that is true at all? Is it because it is a saturated oil? Or is because it is saturated and has short and medium chain fatty acids? Does the oil from butter bypass the liver as well? What about PUFAs that are short and medium chained, will it bypass the liver?
Chris Masterjohn covered this infinitely better than I could.
https://chrismasterjohnphd.com/2017/06/24/coconut-oil-killing-us/

@Kyle M - how'd I do??

 

[DuggaDugga]

Thanks Travis for the answers.

I wonder if you agree with the video. In it, Chris talks about respiratory compensation. He says that high carbon dioxide in the blood causes the breathing rate to increase. The increased breathing rate is meant to increase the rate at which carbon dioxide is expelled to correct for the low blood pH condition that comes with increased carbon dioxide. Based on this reasoning, he says that patients on ventilators would do well to be fed lo-carb hi-fat diets because the reduced carbon dioxide production of fat metabolism would enable them to breath at a lower rate, as there is less carbon dioxide to expel. But would the lower breathing rate of the hi-fat diet be a result of a lower metabolism rate?

I think Chris is proving a very specific example where decreased respiration could be therapeutic in the short term.

 

[Mito]

As medium-chain saturated fatty acids, the majority of coconut oil should go to the liver. I don't think this is necessarily a bad thing.

Coconut oil is almost 85% C12 or longer chain fatty acids. C10 and shorter fatty acids go directly to the liver via the portal vein. Doesn't the majority of C12 and longer fatty acids go through the lymph first before getting to the liver?

 

[Travis]

Coconut oil is almost 85% C12 or longer chain fatty acids. C10 and shorter fatty acids go directly to the liver via the portal vein. Doesn't the majority of C12 and longer fatty acids go through the lymph first before getting to the liver?

In rats it does. There are less studies in humans. This one seems to indicate that palmitic acid is the cut-off point:

The term "A-HV" is used to indicate arterial-hepatic venous and "ƒ" is the fractional uptake, defines as the ratio of the hepatic artery concentration over the general circulation.

This is the best human study that I could find. You don't see many people volunteering to have a cannula put into their portal vein, and another one placed in either their arm or superior mesenteric artery.

Uptake of Individual Free Fatty Acids by Skeletal Muscle and Liver in Man

 

[Mito]

From the studies @Travis posted, it seems lauric acid (C12) is metabolized as both an MCT and LCT but we probably don't know the exact split.

 

[yerrag]

A disabled electron transport chain does this. There can be many causes. For example: errors placed in the DNA encoding for cytochrome c oxidase has been shown to produce these Warburg Effect-like changes. Cytochrome c oxidase, sometimes abbreviated as COX, is integral to oxidative metabolism. It forms the very last last stage as O₂ attaches to its heme iron. Electrons from the heme ring and iron are transferred to oxygen which can then take up H⁺ forming water.
The Citric Acid Cycle stores electrons that it pulls off of pyruvate/acetyl-CoA by placing them on NAD⁺ as hydride [:H⁻] ions. This is a hydrogen with two electrons. These electrons are fed into the electron transport chain and the proton (H⁺) is used to turn ADP and phosphate into ATP and to form H₂O from O₂.

ADP + HPO₄²⁻ + H⁺ ⟹ ATP + H₂O

O₂ + 4e⁻ + 4H⁺ ⟹ 2H₂O

So, what can we do to lessen aerobic glycolysis and increase oxidative metabolism? If cytochrome c oxidase is involved, would this be where red lighting would be of help? What else would help with producting cytochrome c oxidase? Thyroid? Carbon dioxide?

A little of both. On a low-sugar diet, more fat will likely be turned into glucose. But on a 40/40/20 diet, I think most fats would be metabolized using β-oxidation. This is a neat process, and it forms acetyl-CoA directly which can be used in the Citric Acid Cycle and there is no pyruvate required. When reading about β-oxidation, make sure not to confuse the terms "acyl-CoA" and "acetyl-CoA".

You speak well of fat metabolism using beta oxidation. How efficient is beta oxidation as compared to oxidative metabolism? Given that fat is the energy source, would it be reasonable though to assume it will produce more lactic acid as a by-product and less of carbon dioxide?

The absorbtion kinetics are different. At the same chain length, saturated fats are more likely to go to the liver (portal vein). Unsaturated fatty acids are more likely to become phospholipids in the intestines and sent through the lymph. This is partly why a PUFA diet lowers serum cholesterol: the unsaturated fatty acids form chylomicrons and bypass the liver where much cholesterol is synthesized. Cholesterol tends to be packed in higher concentrations in lipoproteins from the liver..

So, saturated fats go more into the liver and unsaturated fats go into the lymphatic system and into general circulation?

I'm also getting the impression that shorter chain fatty acids also get processed more in the liver, and longer chain fatty acids get into general circulation, bypassing the liver.

Would it be fair to say that shorter and saturated fatty acid would more likely get processed by the liver, And longer unsaturated fatty acids are more likely to get into general circulation? If so (and maybe it's just hard to generalize), how does it reconcile with the thinking that saturated fats gets metabolized more easily, and unsaturated fats tend to get stored in adipose tissue? DuggaDugga mentions it takes more enzymes to convert unsaturated fats to energy, and hence that may be a possible cause why there is preference to metabolize saturated fats over unsaturated fats. When unsaturated fats go into general circulation as chylomicrons, and aren't metabolized, how are they converted into fat in adipose tissue? Is it thru the liver also, or is another mechanism involved that doesn't involve the liver?

I'm pretty sure that most bypass the liver to some degree. I think it's helpful to look at the relative amount that goes to the liver vs the amount that goes to the lymph. As medium-chain saturated fatty acids, the majority of coconut oil should go to the liver. I don't think this is necessarily a bad thing.

I've read from Ray that coconut oil tends to cause sugars to be metabolized than to be stored as fat by the liver. Is that what you mean by it not necessarily being a bad thing?

4. When the body is low on sugar, adrenaline and glucagon signals the liver to convert glycogen to glucose. When there is enough glycogen, does adrenaline cause cortisol also be produced?

I think most of us under stress will exhaust our glycogen stores fairly quick.

Thanks for adding further to my understanding with your answers DuggaDugga.

I understand that when you can store glycogen well in the liver, it would take 8 hours of fasting to exhaust them. That's a pretty good amount of time. During this time, I would hope that normal blood sugar levels are maintained and that cortisol won't be needed. Would still be interested in knowing if that indeed is the case.

I think Chris is proving a very specific example where decreased respiration could be therapeutic in the short term.

I'm just not quite agreeing with Chris here though. What he is saying is that too much carbon dioxide production from oxidative metabolism, where sugar and oxygen is burned efficiently, can cause rapid breathing. He says this is because the increased carbon dioxide production in the cells will lead to increased bicarbonate, at which point the blood pH becomes too acidic. And this condition will cause the nervous system to react and initiate respiratory compensation, by which it would cause the person to breathe more in an effort to expel excess bicarbonate.

I see it differently. I do not see anything wrong with a body running purely on oxidative metabolism. It will certainly produce carbon dioxide, but there is no excess acidity that will arise in the blood because the lungs will already naturally expel any carbon dioxide that is deemed to be in excess. This state of interaction precludes the possibility of blood pH becoming too acidic, and this would not trigger respiratory compensation of which he describes.

Why do people hyperventilate? It is a shortage of carbon dioxide or bicarbonate in the blood that causes it. It is because oxygen is not being released to the cells, and the cells are oxygen starved, that it causes the lungs to increase breathing rate. So it is the shortage, and not the excess of carbon dioxide, that triggers increased breathing rate.

Chris is just seeing CO2 differently from how I see it. And how I see it, I think, aligns with what Ray Peat talks and writes about. He sees CO2 as a danger that can arise from the body producing energy from oxidative metabolism, as if there is such a thing as a body burning too efficiently using oxidative metabolism and ending up harming itself. I don't know if that can happen, can it?

 

[Travis]

So, what can we do to lessen aerobic glycolysis and increase oxidative metabolism? If cytochrome c oxidase is involved, would this be where red lighting would be of help? What else would help with producting cytochrome c oxidase? Thyroid? Carbon dioxide?

I read an article once on how CO₂ can increase energy through the electron transport chain. It can do this by stimulating cyclic AMP, which stimulates protein kinase A, which then phosphorylates cytochrome c oxidase. So yes, CO₂ should be able to help.
What is interesting is when respiration increases, then so does the mitochondrial membrane potential. I got the impression from reading the article (full text here) that the membrane potential is directly correlated with the metabolic rate.

How efficient is beta oxidation as compared to oxidative metabolism? Given that fat is the energy source, would it be reasonable though to assume it will produce more lactic acid as a by-product and less of carbon dioxide?

The beta oxidation of short-chain fatty acids can be extremely quick. Moreover, short and medium chain fatty acids can be ω-oxidated as well:

The conversion of 8- to 11-carbon monocarboxylic fatty acids to their corresponding dicarboxylic acids by omega oxidation occurs in man and dog, in vivo (l-5). Omega oxidation, the methyl oxidation of the paraffin end of the fatty acid molecule, in vivo, is restricted to saturated fatty acids of medium-chain length. With these fatty acids, omega oxidation competes with beta oxidation.

In Vivo Enzymatic Omega Oxidation of Medium-Chain Fatty Acids in Mammalian Tissue

...would it be reasonable though to assume it will produce more lactic acid...

Lactic acid is three carbons long. I am fairly certain that it is mainly produced from glycolysis. The oxidation of fatty acids should occur in two-carbon units (acetyl-CoA) except in the rare cases that you ingest an odd-numbered fatty acid (and the glycerol backbone of course).

The metabolism of glucose should produce a higher concentration of carbon dioxide than the metabolism of most fats.

So, saturated fats go more into the liver and unsaturated fats go into the lymphatic system and into general circulation?

If you look at the experimental data, you will see that it's difficult to make any hard-and-fast rules about this. Most fatty acids are partitioned between the liver and the lymph and it wouldn't be unusual to see data like this (liver/lymph):

C₈=(90/10)
C₁₀=(70/30)
C₁₂=(50/50)

And there aren't very many good experiments in humans. It also depends on the fat, and not just the fatty acid. In triglycerides, three fatty acids share a glycerol backbone. These are released at different rates, and the specific fatty acids (and their order) determine the ease at which the digestive enzymes hydrolize them. So it not only depends on the fatty acid in question, but also on the identity of the neighboring fatty acids on the glycerine backbone (triglyceride). So myristic acid in coconut oil will be metabolized differently than myristic acid in olive oil for this reason.

I would say that there is a trend for shorter fatty acids to go to the liver, and another trend with increasing saturation. The saturation trend might not be very significant since it is confounded by the fact that short-chain unsaturated fatty acids are extremely rare. Myristoleic acid (C₁₄) is practically the shortest one you will ever eat. So when someone says that "saturated fats tend more to go to the liver", they are really talking more about the relative incidence in chain lengths between saturated and unsaturated fats than they are talking about the degree of unsaturation (although they may not realize that).

Would it be fair to say that shorter and saturated fatty acid would more likely get processed by the liver, And longer unsaturated fatty acids are more likely to get into general circulation?

Yes. You always see this trend in animal species although it's difficult to say the exact proportions and there can be exceptions. The longer fatty acids are generally reglycerated as phospholipids in the enterocytes. The chylomicrons (and I think VLDL) are put-together in the intestines and bypass the liver (as long-chain phospholipids). These lipoproteins are mostly lipids, and the lipids can transfer from lipoprotein to lipoprotein. They also can be transferred to tissues of course. These can even make their way back to the liver as [I can't remember what] is activated to pull these lipoproteins out of circulation.

The short-chain saturated fatty acids that make it to the liver are metabolized there quickly (from both ends (β and ω)) at rates proportional to the inverse of their chain length. The small molecule products from β- and ω-oxidation can then be sent through the blood as ketones.

Is that what you mean by it not necessarily being a bad thing?

It's just that when people hear the words "fat" and "liver" in the same sentence they get a bit apprehensive.

 

[Mito]

He sees CO2 as a danger that can arise from the body producing energy from oxidative metabolism, as if there is such a thing as a body burning too efficiently using oxidative metabolism and ending up harming itself. I don't know if that can happen, can it?

I don't think he sees CO2 as a danger. He talks about the benefits of CO2 in this video: Carbon Dioxide - Carbs Vs Fat Oxidation

 

[yerrag]

The short-chain saturated fatty acids that make it to the liver are metabolized there quickly (from both ends (β and ω)) at rates proportional to the inverse of their chain length. The small molecule products from β- and ω-oxidation can then be sent through the blood as ketones.

It's just that when people hear the words "fat" and "liver" in the same sentence they get a bit apprehensive.

Tbis makes more sense now. So this is why taking coconut oil is said to give "instant energy" because of its composition being a large percentage short and medium chain fatty acids. That ketone by-products are produced is also good as it can be used by the brain.

Ray also says that coconut oil, and I suppose he meant the short and medium chain triglycerides in it, also encourages metabolism of sugar and helps keeps sugar from being converted to fat by the liver. Would you know the mechanism by which coconut oil makes this happen?

A few more questions, Travis, given that beta and omega oxidation of short and medium chain saturated fats (of coconut oil) is involved here, what are the negatives of these metabolic pathways as opposed to the oxidative metabolism of glucose? I'm asking in the context of some strongly held beliefs in the forum that the less fats are in the diet, the better it is. Is it because beta and omega oxidation ( I gather this to be the best kind of fat metabolism, where short and medium chain triglycerides are involved, with the kidney involved) are less efficient than oxidative metabolism (of glucose)? Or is this because it is just producing less carbon dioxide? Would producing less carbon dioxide necessarily mean producing more lactic acid?

I want to explain also my questions here. Is fat oxidation of the best possible kind (no PUFAs and a surfeit of short and medium chain FAs) considered "bad" because it is relatively inferior to oxidative metabolism? Or is it "bad" because it produces stress conditions such as a high production of lactic acid with little CO2 produced?

 

[yerrag]

don't think he sees CO2 as a danger. He talks about the benefits of CO2 in this video:

I should not phrase it that way. But I wanted to know if I stand to be corrected in not agreeing with what Chris Masterjohn said. Would appreciate your thoughts and if @Travis and @haidut could speak to it as well:

I'm just not quite agreeing with Chris here though. What he is saying is that too much carbon dioxide production from oxidative metabolism, where sugar and oxygen is burned efficiently, can cause rapid breathing. He says this is because the increased carbon dioxide production in the cells will lead to increased bicarbonate, at which point the blood pH becomes too acidic. And this condition will cause the nervous system to react and initiate respiratory compensation, by which it would cause the person to breathe more in an effort to expel excess bicarbonate.

I see it differently. I do not see anything wrong with a body running purely on oxidative metabolism. It will certainly produce carbon dioxide, but there is no excess acidity that will arise in the blood because the lungs will already naturally expel any carbon dioxide that is deemed to be in excess. This state of interaction precludes the possibility of blood pH becoming too acidic, and this would not trigger respiratory compensation of which he describes.

Why do people hyperventilate? It is a shortage of carbon dioxide or bicarbonate in the blood that causes it. It is because oxygen is not being released to the cells, and the cells are oxygen starved, that it causes the lungs to increase breathing rate. So it is the shortage, and not the excess of carbon dioxide, that triggers increased breathing rate.

 

[DuggaDugga]

Tbis makes more sense now. So this is why taking coconut oil is said to give "instant energy" because of its composition being a large percentage short and medium chain fatty acids. That ketone by-products are produced is also good as it can be used by the brain.

Ray also says that coconut oil, and I suppose he meant the short and medium chain triglycerides in it, also encourages metabolism of sugar and helps keeps sugar from being converted to fat by the liver. Would you know the mechanism by which coconut oil makes this happen?

A few more questions, Travis, given that beta and omega oxidation of short and medium chain saturated fats (of coconut oil) is involved here, what are the negatives of these metabolic pathways as opposed to the oxidative metabolism of glucose? I'm asking in the context of some strongly held beliefs in the forum that the less fats are in the diet, the better it is. Is it because beta and omega oxidation ( I gather this to be the best kind of fat metabolism, where short and medium chain triglycerides are involved, with the kidney involved) are less efficient than oxidative metabolism (of glucose)? Or is this because it is just producing less carbon dioxide? Would producing less carbon dioxide necessarily mean producing more lactic acid?

I want to explain also my questions here. Is fat oxidation of the best possible kind (no PUFAs and short and medium chain FAs) considered "bad" because it is relatively inferior to oxidative metabolism? Or is it "bad" because it produces stress conditions such as a high production of lactic acid with little CO2 produced?

Ketones suppress glucose consumption in the brain. Ketones by-pass the pryuvate dehydrogenase complex step and enter the TCA cycle at the citrate level, so the short-comings of fat oxidation apply here as well. Ketones are really a glucose-sparing substrate that were intended to sustain the brain during famine. It's not an ideal substrate for the aforementioned reasons.
KETONES SUPPRESS BRAIN GLUCOSE CONSUMPTION
http://ajpendo.physiology.org/content/297/3/E578

 

[haidut]

enter the TCA cycle at the citrate level

Thanks for this! A lot of people seem violently opposed to this idea.
As for the quote from your post - it is exactly this step that drives cancer growth as well. So, ketosis is really not a good idea for people with this condition. I don't understand why people have such a hard time accepting that we have two primary fuel sources which also serve as environmental signals. When times are good and stress is low we oxidize glucose. (Btw, I think this is probably the primary purpose of the Randle cycle - i.e. to conserve glucose under stress.)
When under stress, and especially when glucose is not enough, we switch to fat oxidation and this fat oxidation causes all sort of adaptations in the organism to reflect the stressful environment - i.e. reduced anabolism, steroid synthesis, fertility, immune function, etc.

 

[DuggaDugga]

Thanks for this! A lot of people seem violently opposed to this idea.
As for the quote from your post - it is exactly this step that drives cancer growth as well. So, ketosis is really not a good idea for people with this condition. I don't understand why people have such a hard time accepting that we have two primary fuel sources which also serve as environmental signals. When times are good and stress is low we oxidize glucose. (Btw, I think this is probably the primary purpose of the Randle cycle - i.e. to conserve glucose under stress.)
When under stress, and especially when glucose is not enough, we switch to fat oxidation and this fat oxidation causes all sort of adaptations in the organism to reflect the stressful environment - i.e. reduced anabolism, steroid synthesis, fertility, immune function, etc.

My thoughts exactly. Each differentiated cell "makes decisions"-- if you will-- based on its energetic state and the stimulus it receives from the environment. I would expect that fatty acids in the blood from low-carb dieting would have similar effects to that of famine and to that of stress. That's obviously a little reductionist because the body/environment will have some differences in each of those circumstances . Point being that the tremendous similarities in each of those circumstances makes low-carb dieting untenable in my opinion.

It's been my experience that excessive fat consumption invariably induces lethargy. Conversely I can snack on fruit all day long and the only "side-effect" is that I'm always hungry and need to frequently satisfy an increased need for nutrient-dense foods like liver, oysters, and eggs.