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  1. #81
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    Quote Originally Posted by dilberryhoundog View Post
    Nassim Taleb
    Thank you!

  2. #82
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    Quote Originally Posted by Derpamix View Post
    The reason why fats produce more ATP coincides with the fact it oxidizes much slower. Fats have to be transported from fat cell tissue to metabolize in form of vesicles, which are taken up through endocytosis and degraded into fatty acids, then finally have to be converted into acetyl CoA before entering beta oxidation. Also, the fact fat contains an enormous amount of carbons and have to have already circulating oxygen in the cells in order to couple further slows this process. Also, fat oxidation produces huge amounts of water, which can burden the cells and respiratory system and cause lactic acid build up to take the place of the missing oxygen for energy, which shortens the ATP produced.

    I'll also assume you're talking about short chained fatty acids, as very long chain fatty acids cannot be used by the mitochondria and produce no ATP(peroxisome beta oxidation)
    Sorry to get back to this so late in the game, but, as it is wont to do, life has a habit of getting in the way of important things like posting here on MDA.

    Let me address your argument, such as it is, piece by piece. I can't promise that I will be linear in my approach, but I'll attempt to at least be comprehensive.

    Quote Originally Posted by Derpamix View Post
    The reason why fats produce more ATP coincides with the fact it oxidizes much slower.
    Proof by repeated assertion is not proof. It is merely annoying. You can chant this mantra until you are blue in the face, and it won't get you anywhere with me.

    You have to be careful when you get your knowledge from Wikipedia ... it may just lead to a superficial level of "understanding." With that said, your understanding of biochemistry is pretty mechanistic and you keep coming back with counts of the number of reaction steps involved in some metabolic pathway vs. another.

    I've already pointed out to you that the number of steps in such reactions is something of a red herring. What is far more important is the rate of reaction, which is to say that a reaction chain comprising several very fast reactions may occur in less time than one consisting of a single, albeit relatively slow, reaction. To this end, I've asked you about the kinetics of the various enzymes involved in oxidizing pyruvate and fatty acids, something that you've cleverly ignored. What I was asking for was velocity vs. substrate concentration curves. I'm fairly certain that these won't be forthcoming, so we'll just move on.

    Again, to reiterate, fats produce more ATP because they contain more carbon than glucose. Glucose is a 6 carbon molecule which metabolizes to two 3 carbon pyruvate molecules via a sequence of 10 reactions (!). Unlike pyruvate fats can be arbitrarily long but typically the predominant form in adipose tissue is palmitic acid, a 16 carbon saturated fat.

    Quote Originally Posted by Derpamix View Post
    I'll also assume you're talking about short chained fatty acids, as very long chain fatty acids cannot be used by the mitochondria and produce no ATP(peroxisome beta oxidation)
    No, I have been, and still am, talking about long chain fatty acids, specifically palmitic acid, where a long chain fatty acid is generally conceded to be fatty acids greater than 12 carbons in length, and less than 20ish carbons where we cross the threshold into very long chain fatty acids (VLC FAs). I fail to understand why you would assume that I would be talking about short chained and not medium or long chained fatty acids, especially as I've been making specific reference to palmitic acid all along? The less charitable side of my personality is prompting me to conclude that that is due to the fact that you don't actually know what palmitic acid is.

    Quote Originally Posted by Derpamix View Post
    Fats have to be transported from fat cell tissue to metabolize in form of vesicles, which are taken up through endocytosis and degraded into fatty acids, then finally have to be converted into acetyl CoA before entering beta oxidation.
    You are confusing triglycerides with fatty acids, and even then, you are quite far off the mark. The only source of triglycerides (TAG) in your plasma comes from dietary fat and as part of its absorption from the digestive system via the lymphatic system, it gets packaged in chylomicrons to render the TAG water soluble and therefore suitable for circulatory system distribution. Fatty acids ( note, _not_ chylomicron bound TAGs ) are how adipose tissue delivers it's contents to the rest of the cells of the body, and these are bound to plasma albumin.

    I was hoping to not have to do this, put you've forced my hand. This is how fatty acids enter a cell:



    So after you've looked at that diagram for a while, I would like you to point to the endocytosis step. Now, obviously, should you accept my challenge, I can't see what you are pointing to. Of course, I don't need to, because there is no endocytosis step depicted. Fats don't enter cells, fatty acids do, and they certainly don't do so by endocytosis, which is why any discussion about insulin and its fat metabolism effects always center on hormone sensitive lipase and lipoprotein lipase, which are the enzymes which liberate fatty acids from adipose tissue, and the enzymes which liberate fatty acids from chylomicrons, respectively as precursors to their uptake or release from cells.

    The reason I was hoping to not have to show the intricacies of cellular fatty acid uptake was because it is easy to get lost in the details. I ultimately went there because your understanding of things is rather odd, to put it mildly.

    And now, we come to beta oxidation. By this point, those that have keeping score should not be too surprised to find out that you have it not just a little wrong, but rather, exactly backwards. Beta oxidation is a 4 reaction chain that produces acetyl CoA from fatty acids for entry into the citric / TCA / Krebs cycle. Now I could beat this dead horse until it is as mangled as your understanding of oxidation, but I really don't see the point, although I will show you a diagram of what I'm talking about ( the bit in the yellow box comprises beta oxidation, the end product of which is AcoA ):



    Once you've formed acety CoA from you substrate, whether that is glucose, fats, or proteins, you have no chance of identifying which of those was the source at the level of the TCA cycle. It's just acetyl CoA, and we're off to the ATP generation races.

    Glycolysis produces two pyruvate molecules from one glucose molecule, which in turn provide two acetyl CoA molecules, sufficient to drive the TCA cycle twice. Every time through the beta oxidation cycle, two carbons are cleaved off the fatty acid, which means that beta oxidation of 16 carbon palmitic acid will provide sufficient acetyl CoA to drive the TCA cycle 8 times. Or, in other words, one palmitic acid molecule provides roughly 4 times the ATP of a glucose molecule upon oxidation.

    Quote Originally Posted by Derpamix View Post
    Also, fat oxidation produces huge amounts of water, which can burden the cells and respiratory system and cause lactic acid build up to take the place of the missing oxygen for energy, which shortens the ATP produced.
    I have no idea what in the world you are trying to say here. Lactic acid build up is caused by water? Are you serious?

    Each molecule of NADH+H and FADH2 that donates electrons to the electron transport chain winds up creating one H2O molecule. Each TCA cycle produces 3 NADH+H complexes, hence 3 molecules of H2O. So, each glucose molecule drives the TCA cycle twice, producing 6 H2O molecules. In addition, the conversion of pyruvate to ACoA by pyruvate dehydrogenase generates one NADH+H complex, and since we get two pyruvate molecules per glucose, the total H2O production from glucose oxidation in the ETC is 8 molecules.

    Beta oxidation produces one NADH+H complex and one FADH2 per ACoA molecule generated, meaning that if you get your ACoA from beta oxidation rather than glycolysis, you generate ... how much additional water? Care to chime in here, Derp? According to you, it's a "huge amount." When I do the math, we get ... two additional molecules of H2O from the additional FADH2 yield. In case you missed it, that's a rather modest increase of 25%.

    If at a cellular level, I have a requirement for, say, 120 ATP molecules, I can either oxidize 3 molecules of glucose, or 1 palmitic acid molecule. They both will yield the 120 ATP that I need, but the oxidation of the palmitic acid will also yield 25% more water. So ... assuming that I will concede that a 25% increase constitutes a "huge amount" of water, I wonder what a threefold increase in cellular water would constitute in your lexicon? Super duper ultra mega huge amount? What am I talking about? Well, if you recall, glucose and its metabolites are water soluble, which means that as they get sequstered or accumulate in a cell, they increase osmotic pressure, with the net result that water is driven into the cell. This is the by now well worn observation that for every gram of glycogen, you carry an additional 3-4 grams of water, the source of the miracle behind ketogenic diets, etc. etc. So, if we were playing water retention poker, at this point, I'd see your 25% and raise you 300%.

    There is so much here that is so wrong that I could go on, if I weren't limited to 10000 characters in a single post. So, I'm just going to stop. It's a little like shooting fish in a barrel.

    -PK
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    Interested in Intermittent Fasting? This might help: part 1, part 2, part 3.

  3. #83
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    Quote Originally Posted by Neckhammer View Post
    Ah, but that begs to question.... is placebo (state of mind, belief, meditation, positive thinking....whatever) simply the strongest medicine with no side effects!

    You know I wonder if there as been any experiments aimed specifically at enhancing the placebo effect? Like a single blind trial with three arms placebo, placebo + doctor "letting it slip" that you are in the group getting the drug, and drug groups. Could be interesting to see how much we can maximize the placebo effect.
    These experiments have been done. I will see about digging up some references for you. I also believe that Ben Goldacre has an entire chapter on this in his book, Bad Science. Placebo pill color matters, for instance, with I believe dark, somber colors like red having more of an effect than blue, for instance.

    Placebo injections work better than placebo pills, irrespective of color. The more pomp and circumstance associated with a placebo the more effective the placebo, which goes a long way towards explaining how a voodoo priest / witch doctor can kill people merely by sticking a pin in a doll.

    -PK
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  4. #84
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    It took you 2 weeks to come up with that?

    I already knew everything you said, the only thing you managed to do is take a little post of mine and turn it into a copy and paste from google scholar fest(I checked), and cherry picked parts to post against.

    It's not mantra, when you compare the huge amount of carbons, then consider you have to separate the hydrogens from the carbon atoms, break the oxygen molecule apart, then recombine all those atoms to make co2 and h2o. It takes hundreds of small reaction steps. But, whatever you say...

    Since you ignored it the first time, I said fatty acids, degraded, not fats, again: before fatty acids can be oxidized, they must first undergo a priming step. Fatty acids in the cytoplasm must cross the mitachondria membrane before the oxidation begins; this was the point I was eluding to. The overall initiating step is the reaction of the fatty acid with coenzyme A. This reaction requires energy and is therefore coupled with the hydrolysis of ATP to AMP. The activated long chain fatty acid is carried across the mitochondria membrane by carnitine. And this is a very shortened version after the fact.

    It should be obvious why fat oxidizes slower. Of course, it's mantra to you, but you haven't proven otherwise, you just showed the steps of beta oxidation repeatedly(gee thanks)

    Because I was being generous and decided to give you the benefit of the doubt, as long chain fatty acids were in my last post which quote you removed. The whole part about cleaved fatty acid uncoupling, and mitochrondria dysfunction, induced membrane "leakiness", and shortened ATP production, ergo, co2, by wasting it, via many ways, which is what this whole argument was about.

    That last part :eyeroll:

    Your reading comprehension sucks. The rest of this crap isn't worth responding to, because I have no idea what you're trying to say, because half that shit is just presumptuous. Are you schizophrenic perhaps?
    Time is passing so quickly. Right now, I feel like complaining to Einstein. Whether time is slow or fast depends on perception. Relativity theory is so romantic. And so sad.

  5. #85
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    Quote Originally Posted by Derpamix View Post
    It took you 2 weeks to come up with that?

    I already knew everything you said, the only thing you managed to do is take a little post of mine and turn it into a copy and paste from google scholar fest(I checked), and cherry picked parts to post against.

    It's not mantra, when you compare the huge amount of carbons, then consider you have to separate the hydrogens from the carbon atoms, break the oxygen molecule apart, then recombine all those atoms to make co2 and h2o. It takes hundreds of small reaction steps. But, whatever you say...

    Since you ignored it the first time, I said fatty acids, degraded, not fats, again: before fatty acids can be oxidized, they must first undergo a priming step. Fatty acids in the cytoplasm must cross the mitachondria membrane before the oxidation begins; this was the point I was eluding to. The overall initiating step is the reaction of the fatty acid with coenzyme A. This reaction requires energy and is therefore coupled with the hydrolysis of ATP to AMP. The activated long chain fatty acid is carried across the mitochondria membrane by carnitine. And this is a very shortened version after the fact.

    It should be obvious why fat oxidizes slower. Of course, it's mantra to you, but you haven't proven otherwise, you just showed the steps of beta oxidation repeatedly(gee thanks)

    Because I was being generous and decided to give you the benefit of the doubt, as long chain fatty acids were in my last post which quote you removed. The whole part about cleaved fatty acid uncoupling, and mitochrondria dysfunction, induced membrane "leakiness", and shortened ATP production, ergo, co2, by wasting it, via many ways, which is what this whole argument was about.

    That last part :eyeroll:

    Your reading comprehension sucks. The rest of this crap isn't worth responding to, because I have no idea what you're trying to say, because half that shit is just presumptuous. Are you schizophrenic perhaps?
    Regarding the bolded part, I'm really curious how you did this.

    My assumption is that you put in a few search terms (I'm sure you can remember), and found specific articles. Could you link those?

    I'm also assuming that when you say (I checked) you really did, that's why I'd like further information.

  6. #86
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    Quote Originally Posted by Derpamix View Post
    Elided Effluvium Excerpted below
    Good morning, Derpie!

    You are labouring under a misconception, namely that in a public forum such as this you are actually speaking to me, when in fact, you are not. You are in fact speaking to a much larger audience that will judge you on the merits of what you say and how you say it. With that in mind, one sure way to lose ground is to resort to insulting me personally, so, for example, calling me schizophrenic. This tactic is useless, as I do not care about your opinion of me, because in order for that to matter, I would have to hold you in some esteem, and I do not. So you cannot score points with me, and as regards the larger forum base, either I am schizophrenic, at which point you look cruel, or I'm not, which makes you look petty and juvenile.

    The way to actually sway someone to your point of view is with specific rebuttals of things that your opponent has said. As an example, when I say that there are hundreds of reaction steps involved in fatty acid oxidation, you would point out that beta oxidation only involves 3 additional steps relative to pyruvate. At the end of one cycle of the four reactions of beta oxidation, you have one molecule of acetyl CoA, and a fatty acid that has been shortened by two carbons. The acetyl CoA molecule then enters the TCA cycle in an identical fashion as would an acetyl CoA produced from pyruvate, albeit in the case of pyruvate there is only one reaction needed. It is true that the remaining shortened fatty acid can once again participate in the four reaction steps of beta oxidation, but at this point, you are effectively in a "pure profit" mode, as you are now generating more energy than would be possible from pyruvate.

    Because verbal explanations of biochemical pathways can get rather involved, to help clarify matters it might be useful to provide a diagram of the various biochemical pathways, like beta oxidation, the TCA cycle, and electron transport chain so that people so inclined could actually count the number of steps involved. Upon realizing independently that there were not hundreds of reaction steps involved, your opponent's credibility is eroded. Your problem here, of course, is that you are the one who is saying that there are hundreds of reaction steps, whereas I am the one saying that there are only a handful of additional ones when it comes to fatty acid oxidation:

    Quote Originally Posted by Derpamix View Post
    It's not mantra, when you compare the huge amount of carbons, then consider you have to separate the hydrogens from the carbon atoms, break the oxygen molecule apart, then recombine all those atoms to make co2 and h2o. It takes hundreds of small reaction steps. But, whatever you say...
    Even if it were to take 20, 30, or maybe even 40 additional steps, the claim here is that it takes hundreds, the plural form making that at least 200 more, which makes the claimant seem prone to exaggeration and hyperbole, which again would serve to undermine credibility.

    Another approach to swaying people, especially when dealing with a very well elaborated scientific topic, is to point out where your opponent is using vague terminology, because that is indicative of muddled understanding. To reuse our example above, then, hundreds is very vague and smacks of hucksterism, precisely because nobody has any idea how many "hundreds" is. The number of reaction steps is deterministic. You can count them, if you actually understand the biochemistry.

    Another effective tactic is to show how your opponents thinking is sloppy and incomplete in general. For example:

    Quote Originally Posted by Derpamix View Post
    Since you ignored it the first time, I said fatty acids, degraded, not fats, again: before fatty acids can be oxidized, they must first undergo a priming step. Fatty acids in the cytoplasm must cross the mitachondria membrane before the oxidation begins; this was the point I was eluding to.
    This statement is true, but it applies equally well to carbohydrates, as pyruvate is shuttled across mitochondrial membranes by a transport protein. Moreover, pyruvate is the end product of a 10 reaction glycolysis process, which would certainly fall under the umbrella of an order of magnitude larger number of "priming steps" than fatty acids. All in all, that renders the argument moot, more of a case of six of one and a half dozen of the other.

    Although not nearly as suasive, you can point to your opponents overall sloppiness such as when they say elude when they actually mean allude. Although, the use of elude is actually quite amusing in a Freudian slip sort of way, when you consider that it can mean "failing to grasp", which actually would serve to make that read "this was the point that I was failing to grasp." Perhaps your subconscious is trying to tell you something? Nevertheless, you can then attempt to make a case for this sloppiness being pervasive in your opponent's thinking and presentation.

    It is also very helpful if you can point out how your opponent has misunderstood the basic science to which they claim mastery (i.e. "I knew all of that" ). So, when your opponent claims that the formation of acetyl CoA from fatty acids is a prerequisite input to beta oxidation, when in fact the whole purpose of beta oxidation is to form acetyl CoA from fatty acids as an input to the TCA cycle, you point that out. Again, diagrams are useful because they allow readers to make independent judgements, apart from merely accepting the opinion and provably incorrect assertions of your opponent.

    If you can establish that your opponent is prone to histrionics, that can be useful as well. It's actually really helpful if your opponent is generally defensive and prone to making accusations such as accusing you of "cherry picking." In such a case, you could point out that you were engaging in a process of rebuttal. That process is a refutation of specific points your opponent made that are false. To address these points rather than banal yet true assertions such as "oxygen makes bananas brown eventually" does not constitute cherry picking in any sense.

    A very effective technique is to ask direct questions of your opponent. Obviously, when they fail to answer them, they look increasingly less credible. Examples would be:

    "What are the relative rates of reaction of the enzymes involved in beta oxidation, and how does that compare to the rate of reaction of pyruvate dehydrogenase?"

    "How much more water is produced per unit of energy generated ( molecule of ATP ) by beta oxidation?"

    That last question represents a very effective technique because it constitutes a simultaneous attack on two fronts. First, it is the very specificity of the question that is most damaging because it requires deeper understanding of the subject matter, making it much less amenable to a quick internet search. As a result, an opponent with a superficial understanding will find it difficult to answer. But, assuming that they can muster an answer, the second and more subtle part of the attack lies in the answer itself, because it will directly contradict other statements made by your opponent. So either your opponent fails to answer the question, which erodes their credibility, or they manage to answer the question, which serves to erode their credibility.

    Lastly, as a rhetorical technique, profanity can be effective, although its effectiveness is inversely proportional to the frequency with which it is used. From what I've seen of your tendencies, you might consider that you are overusing this technique. Nevertheless, it is interesting that you dismiss out of hand replying to the majority of what I had to say on the basis that "half that shit is presumptuous." Apart from the fact that this is merely vacuous opinion lacking a preposition, I don't think presumptuous means what you think it does. My dictionary has it that a presumptuous person is one whose behaviour fails to observe the limits of what is permitted or appropriate. The juxtaposition of that word with your scatological expletive is again unintentionally, I'm sure, quite amusing.

    Since you feel entitled to speculate as to my psychological condition, I expect you would extend the same courtesy to me, so I shall speculate in return. Perhaps you never got over the anal fixation stage of childhood development? Or maybe behind that avatar really lurks a precocious toddler? That would truly be something and explain many things.

    -PK

    P.S. I regret that post length limits preclude my quoting you verbatim. Luckily, folks can scroll back to get a sense of your thinking process.
    Last edited by pklopp; 06-13-2013 at 07:05 AM.
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  7. #87
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    Quote Originally Posted by jackaaron View Post
    Regarding the bolded part, I'm really curious how you did this.

    My assumption is that you put in a few search terms (I'm sure you can remember), and found specific articles. Could you link those?

    I'm also assuming that when you say (I checked) you really did, that's why I'd like further information.
    Word to the wise, you are dealing with someone for whom :eyeroll: constitutes a valid argument. You are probably in for some disappointment.

    -PK
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  8. #88
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    If I were a gambling man I would give about 30 to 1 odds that I will get a relevant answer. And relevance would be quite easy for those involved to determine,however its likely I would not get any action.
    Fortunately I'm not this type of gambler lol.

  9. #89
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    Face it, Derpums. If you go up against PK on the science, you're gonna get schooled.

  10. #90
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    You are visibly upset. I have no desire to engage in a pissing contest with a pseudo-intellectual blowhard, but after actually spending 2 minutes to skim over it, I can see what area I slipped up at, and where you're coming from with that whole post. When I was cutting and pasting from notepad, I left one thing in the wrong spot, while attempting to get the scientific jargon in order. I'm sure, as someone familiar to copying and pasting, you can understand. So, let's just nip this in the bud. It really should have read from fat metabolism, going from the original carbon part, then to acyl-coa in the cleavage stage of beta oxidation, to show the complexity of oxidating fats for co2, but somewhere along the line I messed it all up(I was admittedly tired that night). This was in my notepad: "finally acetyl-CoA is cleaved off with thiolase to yield an acyl-coa that is two carbons shorter than before. The cleaved acetyl-CoA can then enter into the TCA and ETC" but I figured you'd already explained beta oxidation enough and was only looking to show the energy wasting aspects of it anyway. It was more of an attempt at hyperbole on my part again, because, if I can make it look really fucking long maybe someone will look at it and go "holy shit fats are so complicated this guy is right I'm not reading that"

    It's kind of the same with all your picking and choosing of ATP output without a real fundamental knowledge on the real intricacies and variables involved. But, I guess we were only after an analytical hypothesis anyway.

    Admittedly, I could have formulated a much better argument against you had I actually paid attention, but I never really did. This part isn't an attack on your integrity, because you clearly really tried hard, but more of a fault of my own. I often stumble on here half dead from work, and usually don't come across people who spent the 30 minutes reading on google that you have, so, it caught me a little off guard.

    I'll be the first to admit I don't actually read your posts, because they're really boring, drawn out for no rhyme or reason, and I can find equal stimulation from flipping through a thesaurus, since this is definitely among your writing style. I'm all too familiar with it, having taken Lit 101 in community college.

    Nice paragraphs of ad hominems though, this will definitely make Paleobird fantasize about your avatar more. Sadly, I'm not very impressed, so if you were looking to get me riled up by these posts, your avatar, and that passive gay comment, combined with a creepy child reference, you're going to have to try a little harder, as I'm not easily impressed.
    Time is passing so quickly. Right now, I feel like complaining to Einstein. Whether time is slow or fast depends on perception. Relativity theory is so romantic. And so sad.

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