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Please Help Me Understand Aerobic Energy Production

Discussion in 'Post-Exertional Malaise, Fatigue, and Crashes' started by pone, Jun 4, 2014.

  1. pone

    pone

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    I am trying to better understand aerobic energy and what is breaking down in the case of CFS. Unfortunately, I don't have the science background on aerobic respiration, and I am getting lost in biochemical equations. I need a higher level picture.

    This article describes three types or "stages" of aerobic energy named glycolysis, krebs cycle, and electron transport:

    http://www.buzzle.com/articles/aerobic-and-anaerobic-respiration.html

    This article confuses me because they list the first step as glycolysis, and then they say glycolysis does not need oxygen. Well, that would be anaerobic glycolysis, not aerobic glycolysis? What am I not understanding there? Based on their description, it sounds like there is no glycolysis that requires oxygen? Why would they describe an anaerobic process that requires glucose in an aerobic metabolism section of the article?

    What about krebs cycle and electron transport? Are those used side by side at the same time in the same tissues? Where can I get a good overview of what these are and how they are used that does not immediately become a textbook on biochemistry? Just seeing something at a high level would be really helpful before I dig into details later.

    Now here is where I get even more confused: at what point does fat start being used instead of glucose, and is that fat being used in krebs cycle, electron transport, or yet another process that is aerobic?

    And, finally, what are the current best theories about which of these processes are breaking down for a CFS patient? I gather that much of the problem is about NADH (which is the output of many of these processes) not being able to convert back to NAD+. Is that sufficient to explain all of the post exercise malaise symptoms?
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  2. rwac

    rwac Senior Member

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    Glycolysis occurs in both aerobic and anaerobic conditions. In aerobic conditions, it produces pyruvate which is further converted to Acetyl-COA and processed by the krebs cycle (aka citric acid cycle) to release lots of energy and ends up as CO2.

    In anaerobic conditions, the pyruvate is converted to lactic acid. This is inefficient compared to aerobic phosphorylation. This is also called fermentation, which is the process by which bacteria produce lactic acid(yogurt) or ethanol(beer, wine, etc).

    Fatty acids are handled by a different process called beta-oxidation. This process produces Acetyl-COA which is then processed by the krebs cycle.

    One theory is that PEM occurs because of excess lactic acid after exercise. Normally the liver should be able to remove and store it. However, we have generally inadequate glycogen storage, and the liver doesn't work as it should. Exercise itself uses up stored glycogen as well. In addition, we may have elevated levels of D-lactate from gut dysbiosis which is a metabolic burden and isn't usable by the body. Putting this load on the liver results in reduced detoxification of other toxins as well.
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  3. WillowJ

    WillowJ Senior Member

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    This might be a simplified enough link:
    http://www.uic.edu/classes/bios/bios100/summer2002/lect10.htm

    Basically what we have in the buzzle article is cellular respiration, following the stream which begins with glucose (which can come from sugars or carbohydrates). Aerobic respiration is explained in several steps, and anaerobic respiration is not really explained what steps are involved and why.

    Rundown on aeroboc respiration in the stream beginning with glucose (this has some chemistry but hopefully explained enough):

    The first step, glycolysis, takes place in the cytoplasm. Each glucose molecule is split into two molecules of pyruvate. Two ATP were used and four resulted, for a net gain of 2 ATP. (ATP <=> ADP; it is a phosphate group with a high-energy bond which is exchanged).

    In the process, two NAD+ gained electrons (and a hydrogen atom) to become 2 NADH. (Carrying the electrons is the function of the NAD+/NADH molecule--such transferrable electrons and the high-energy bonds they are involved in can be viewed as stored energy).

    The second step, the citric acid cycle or Krebs cycle or tricarboxylic acid cycle, takes place in the matrix, or inside spaces, of the mitochondria. In the preliminary step 2 pyruvate are converted, transforming 2 more NAD+ to 2 NADH, and ending with 2 AcetylCoA.

    Then the AcetylCoA enters the actual citric acid cycle, which begins by adding a 4-carbon molecule, oxaloacetic acid, to AcetylCoA (2 carbons) to make citric acid (6 carbons). As various things happen, 4 CO(2) are generated (causing the loss of 2 carbons from each molecule in the two hydrocarbons we are currently tracking--the ones which entered as AcCoA) and eventually these molecules will again be oxaloacetic acid (4 carbons), ready for a new AcCoA (2 carbons).

    Also generated are 6 NADH, 2 ATP, and 2 FADH(2) (a molecule similar to NADH).

    So far we have not generated much ATP. 2 from Glycolysis and 2 from the citric acid cycle.

    The third step, the electron trasport chain, takes place embedded in the inner membrane of the mitochondria. It accepts all 10 NADH and 2 FADH(2) produced during the earlier steps and uses these to produce a net of 32 ATP, and reduces oxygen to water.

    So the total net ATP production during aerobic conditions is 36 ATP per glucose.

    During anareobic conditions, the electron transport chain gets backed up because there is no oxygen. So it stops accepting NADH and FADH(2). So there is a lack of NAD+ and of ATP. There is a surplus of ADP and perhaps AMP as well (when things get desperate, some ADP will convert to AMP).

    That's when changes have to be made for anaerobic conditions. Again this is specific to carbs/sugars.

    The first step, glycolysis, takes place in the cytoplasm. Each glucose molecule is split into two molecules of pyruvate. Two ATP were used (forming ADP) and four ADP gained a phosphate group and a high-energy bond, for a net gain of 2 ATP.

    In the process, two NAD+ gained electrons (and a hydrogen atom) to become 2 NADH. (Carrying the electrons is the function of the NAD+/NADH molecule--such transferrable electrons and the high-energy bonds they are involved in can be viewed as stored energy).

    The second step, lactic acid fermentation, takes place in the cytoplasm. The pyruvate is converted to lactic acid, and the NADH is converted to NAD+, allowing the first step to run again. No ATP is generated here.

    So the only ATP generated during anarobic conditions is 2 (net) per glucose, a very poor return. (compared to a net of 36 from aerobic conditions)

    http://cellularrespiration.net/glycolysis/

    However, given enough time, and given some ATP, and preferably the cessation of conditions that led to the anaerobic state, the lactic acid can be sent to the liver and used to generate pyruvate in the Cori Cycle, and depending on cellular conditions the pyruvate could be run through the citric acid cycle or even used to make glucose.

    Metabolism of fats enters this stream of cellular respiration after the fats have been converted to AcetylCoA during the Fatty Acid Spiral (so this enters just ready for the Citric Acid Cycle, then can proceed to the Electron Transport Chain). Since they don't normally make pyruvic acid, they might not be involved in anaerobic metabolism but I would need to do some checking to be sure.
    http://www.elmhurst.edu/~chm/vchembook/630proteinmet.html
    Last edited: Jun 7, 2014
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  4. alex3619

    alex3619 Senior Member

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    Putting it simply, for those who don't want to read the nice explanations here, glycolysis and the Krebs (citric acid cycle) are anaerobic, but eventually feed into the electron transport chain which uses up oxygen, and so is aerobic.

    Beta oxidation is also anaerobic. One of the traps in the biochemistry terms is that oxidation does not have to mean involving oxygen. I think oxidation can involve a gain of oxygen or a loss of hydrogen. Beta oxidation involves a donation of hydrogen to NAD or FAD.

    So oxidation and aerobic can refer to two different things.
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  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i see it like a seesaw, theres always going to be anaerobic and aerobic metabolism going on at the same time but the percentages of what is used changes as does the total energy used.
    Sitting in the lounge chair is aerobic but burning low amounts of fuel, when u jump up then its anaerobic metabolism and then walk off and your mostly aerobic metabolism but burning more energy then when sitting in the lounge chair.

    Maybe we could classify things into low burning aerobic metabolism ie lounge time watching tv, maybe do some dishes etc. things that use low energy for short period of times. Higher intensity aerobic metabolism where one mows the lawn or goes for a walk for 30-60min hike. high intensity would be those doing 5 and 10km runs, these would be high intensity aerobic metabolism. Theres going to be low levels of anaerobic metabloism going on. A sprint for the finish is going to change energy over to anaerobic At the end of the run u start to stride out and sprint home, anaerobic metabolism kicks up a notch and takes over the main energy productiuon. But its not an all or nothing. SO one is at the factory to lift 20kg bags of cement onto a truck, so its an explosive need for energy that become anaerobic, as they are picked up AND PUT on the truck, one has to stop regularly to rest up and continue to going, this is requiring anaerobic metabolism.

    So i think the low burning aerobics is mostly ok for many cfsers but medium to high aerobics no.low to medium anaerobic energy being used can still be used by some with plenty of rest between bouts of work/exercise. For some reason more can handle this than medium intensity aerobic work.
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  6. pone

    pone

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    Okay, now this is all clear. They should have you rewrite the article I quoted. :)

    So devil's advocate reply:

    1) The studies by Workwell Foundation seem to show the problem is with aerobic exercise NOT anaerobic. That strongly implies that perhaps we never get past aerobic glycolysis. Has no one studied the muscle of CFS patients after exercise and tried to biopsy to see if there are markers of specific types of metabolism?

    2) I do not believe the problem is with glycogen. I get in trouble even with small amounts of exercise that could not possibly exhaust glycogen. The acid is not metabolizing out of the muscle.

    3) I have heard about the D-lactate issue but most of the literature on this associates the D-Lactic Acidosis problem with people who either had bowel shortening surgery, gastric bypass operations, or genetic deformity of the small intestine. The other thing that makes me suspicious it could be the gut bacteria is how do we explain that the problem happens only after exercise, and concentrated in the muscle? D-Lactic Acidosis would always be systemic, due to leaky gut, not focused inside muscle. And under what theory do lactobacillus bacteria in the gut suddenly become hyperactive during aerobic exercise of the host organism?

    It's worth testing for D-Lactate for sure (which is a different test than Lactic Acid), but I'm skeptical it would explain the symptoms.

    I'm still just amazed that sports physiologists aren't doing biopsy and metabolic studies on CFS patients during exercise.
  7. pone

    pone

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    Again confusing because this article says aerobic glycolysis does not require oxygen. Then how can we call it aerobic?

    Is it correct that anaerobic "fermentation" is identical to anaerobic "glycolysis"?

    Based on the description, it sounds like the problem for CFS might be somewhere between Krebs cycle and electron transport chain? It's hard to believe that the CFS patient is actually producing those 32 ATP that are the output from the electron transport chain? You kind of allude to this point in a different way. Are there any studies that look at this issue in detail for CFS?
  8. pone

    pone

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    Can you give specific examples of medium to high aerobics that you have heard of people enduring? How much distance/effort/time? What kind of symptoms did they have after that? How much rest time?
  9. alex3619

    alex3619 Senior Member

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    The problem with most of the earlier energy studies is they studied mild patients at rest. What Workwell/PFL did was study output from exercise, then repeat output the next day. The Light's research shows massive shifts in cytokines after exercise. So our cytokines can look normal(-ish) at rest, but are fubar after exercise.

    It has to be recalled that there is almost no money to research CFS or ME, and very little interest in the scientific community. It is also important to know that strong evidence that ME or CFS involves failures in exercise capacity is only about seven years old. Its also probably being missed by most researchers.
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  10. pone

    pone

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    Seems like low hanging fruit for a sports physiologist researcher. They could advance a major understanding of the disease, and possibly identify types of exercise that bypass the problem partially.

    I also don't understand how big pharma would not find this an incredibly juicy target. There is the possibility of being able to treat patients for decades.
  11. alex3619

    alex3619 Senior Member

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    Big pharma wont invest a cent until they have a drug target and outcome measures. We have neither.

    Recall that one of the most celebrated scientists in the world, the most famous virus hunter, Ian Lipkin, could not get a grant approved for a mere one and a half million to do a gut biome study in CFS. He had to come to us for crowdsourcing. What chance does an unrecognized exercise physiology researcher have to get funding?

    Recall also that CFS researchers have lost their academic tenure (almost unheard of), and been threatened with legal action by their universities over bizarre minor things. There is huge bias against funding CFS research, and by huge I mean prohibitive bias.
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  12. Sidereal

    Sidereal Senior Member

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    @pone , here's a personal testimony about the kinds of, shall we say, extremely bizarre institutional obstacles people who try to do biomedical research on this disease face:

  13. alex3619

    alex3619 Senior Member

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    @Sidereal, that was the testimony I had in mind. Thanks for posting that.
  14. Lynne B

    Lynne B Senior Member

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    Oh dear, oh dear, oh dear... But before we dissolve into a puddle on the floor, can we consider the number of good universities, like Queensland's Griffith University, where good work is being done on ME/CFS and get some fire back into our bellies? Still working in metaphors, what do a few ignorant deans amount to in the overall scheme of things but a hill of beans?

    Good grief, time to end here!
  15. rwac

    rwac Senior Member

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    Aerobic exercise is a bit of a misnomer. It just means that lactic acid is being cleared away at the same rate it is being produced. It does not mean that we're fully using aerobic energy production. Aerobic exercise is generally more stressful because you do it for much longer than anaerobic.

    And how do you know what your glycogen stores are normally like? For instance hypothyroid people have trouble storing glycogen. Do you get hypoglycemic symptoms, dizzyness, shakiness, anxiety etc ? That's generally caused by gluconeogenesis kicking in to make glucose from protein (via glucagon and cortisol) when your glycogen stores are empty.

    Well, all the stresses add up. And stress due to aerobic exercise can make the gut leak even more and dump toxins from the gut into the system. Yes, I guess it's not directly related.

    Yes, I suppose they should be.
  16. pone

    pone

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    But it's not a few ignorant deans. Academia is filled with Sh*theads, who actively work against the truth, actively work to suppress the research that is adversarial to their point of view, actively suppress research that is politically unpopular, etc. Ultimately, there is no difference between deans like the ones described in this video, and the church that suppressed the science of Galileo. The progress of mankind has been very slow, because mankind is a stupid and petty species. It's just sad.
  17. pone

    pone

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    Perhaps the issue the Workwell group uncovered is that the first eight seconds of anaerobic exercise - when the energy supplied is from ATP and Creatine Phosphate - does not produce acid byproducts because it is not using glucose metabolism?

    So the advice there might actually be to find forms of exercise - like weightlifting - where you can do eight seconds of intense exercise, followed by two minutes of rest to recover Creatine Phosphate stores, without creating a lot of acid that may not be metabolizing out of muscle.

    I know because I do exercise that involves high and intense energy, like sprinting and swim sprints. Believe me you know when you have glycogen, and you know when you don't have it. It enables enormous powerful muscular movements.

    At first I thought I had a glycogen storage disease. It was only after months of living with it, experimenting with exercise, and using alkaline fluids to neutralize the acid from muscle and body that I clearly understood that my glycogen was there all along. It was the acid stuck in my muscle that was creating the muscular fatigue. At this point my symptoms are probably only 40% as severe as what they were, and after three days of clearing acid my muscles feel very intact and powerful again. Before I learned to take alkaline solutions, the muscle never cleared the acid fully. My muscles went between very fatigued and nearly immobile.

    The bottom line: do you have high d-lactic acid? I plan to get checked for it, but do any CFS patients report a test as high on D-Lactic acid? Is it a significant percentage?

    It's easy to test for. Proof is in the accumulated test results.... Is it isolated or common? If it is not common, then unlikely it is a cause of CFS.
  18. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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  19. WillowJ

    WillowJ Senior Member

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    You're right, that part was confusing.

    Gycolysis is done in both anaerobic and aerobic conditions, then depending on cell conditions there is a choice (for any given molecule of pyruvate, a product of glycolysis): we can either enter the Krebs cycle headed for electron transport chain (aerobic, generating more ATP), or we can do lactic acid fermentation (anaerobic) which does not generate any more ATP but does return NADH to the NAD+ form (using the energy which had been stored in NADH in the process) so we can run glycolysis again (getting 2 net ATP from each glucose, which is not much but better than nothing).

    Yes, agreed, we seem to have a problem running the Krebs cycle or the electron transport chain, or both. Probably the electron transport chain because we do not seem to compensate by burning fat (as we are not fatless as a group: though I suppose there could be subgroups). So this could implicate the mitochondria, I think.
    Last edited: Jun 7, 2014
  20. WillowJ

    WillowJ Senior Member

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    I think it depends a lot on how well people are at the time. I was able to do a sport during a remission, but I took a lot of breaks and didn't go fast. I still got dizzy. When I first got ill I, (after recovering from the flu) stupidly continued running and otherwise going on with life as usual, but I was almost fainting all the time (I didn't understand why, lol... now i know these things). Other times I was able to take short walks. Right now i can't do anything like that, but I am much worse as compared to when I was able to run or even take short walks.
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