Talk:Citric acid cycle

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A simplified view of the process[edit]

The simplified view is still too complex for a non chemist to understand. I have an engineering degree with basic chemistry qualification (British O-level), and it makes no immediate sense to me. Why is this an essential process for all living cells? This statement needs to be substantiated in layman's language. — Preceding unsigned comment added by BWernham (talkcontribs) 05:16, 16 September 2011 (UTC)

Perhaps, an easier understanding of this process would be to say that this cycle reverses photosynthesis to release sunlight energy[usually] for metabolism ie CO2 + water + sunlight energy = carbohydrate + O2 = CO2 + water + energy [ATP etc][ Krebs cycle]. Admittedly, this is an oversimplification, but this is the general purpose of Kreb's. — Preceding unsigned comment added by Kochay1 (talkcontribs) 08:26, 20 February 2014 (UTC)

Why is this an essential process for all living cells? Asking "Why?" in biology is a problem; everything was here -- everything had been "invented" -- before we got here. So just ask "What?" , what is so essential about this process of taking the product of, say, sugar breakdown and oxidizing it all the way down to carbon dioxide and water? You already know the answer, when one phrases it that way: You need to oxidize some fuel; you just do; that's what life requires. No argument there, no discussion needed. The fine points of how living cells further oxidize their fuel , after the initial breakdown of glucose (or other reduced substrate) to this acetyl-CoA molecule-- which is the equivalent, very loosely put, of bucking trees into stove-length firewood --- is pretty intricate, almost a science in itself (mitochondriology). It's not necessary to an understanding of Life to master, or even grasp, even the fundamentals of this process, other than that it does not raise the temperature or pressure of the surroundings (an engineer should be really impressed by that statement) and the yes, it is Universal. Let me repeat that: The Krebs Cycle or TCA Cycle or citric acid cycle is ... a Universal. Just about all the organisms on our planet are the same under the hood, running the Krebs cycle. That is almost unbelievable, since we believe that there are so many differences amongst all of Mother Nature's critters, both flora and fauna and bacteria; but the fact is, they're all running the Krebs cycle. It would be as if every single motor vehicle on Earth were to be running the same model of Cummins Diesel --- just the bigger vehicles would have two or three of them (more like two or three hundred! there are LOTS of mitochondria) and the smallest ones would have the two cylinder version (and all of them would be engineered for >90% efficiency, not the 30% that we have under the hood out on the Boulevard.) — Preceding unsigned comment added by Richard8081 (talkcontribs) 16:48, 24 September 2012 (UTC)

Why not put "A simplified view of the process" before "Steps"? That's the usual order in explaining something. --Nbauman (talk) 18:13, 26 December 2009 (UTC)

My problem is that the article seems to say that all Krebs cycles are the same (identical) for all of the Animal Kingdom. That is a shocker. Including ants? Dust mites?
I read that "cats create their own Vitamin C." I know "citric acid." But the writer was intending the information to be unique to cats and this article definitely makes no distinction except for plants. Is that correct? Student7 (talk) 22:40, 16 October 2011 (UTC)
I think I might edit this soon publicly. But for slight clarification here, the process is essential for continuing the breakdown of sugars to molecules usable for energy in the body (Namely ATP, and the NADH that is reduced (generally means activated for use elsewhere to drive other biochemical processes). It should probably should be stated this is the typical biochemical process that directly follows glycolysis. As of the current version though, at least I don't see anything about cats. Newmanrs (talk) 04:49, 27 October 2011 (UTC)
I have made an attempt to simplify the lead as well as put the TCA cycle in better context. Concerning cats, please note that Vitamin C = ascorbic acidcitric acid. Hence the question concerning cats probably is best directed here. Boghog (talk) 18:37, 27 October 2011 (UTC)
What I was hoping for is a declaration or disclaimer about applying to the entire animal kingdom equally as described herein. Student7 (talk) 19:14, 28 October 2011 (UTC)
All aerobic organisms including all animals, all plants, and most bacteria rely on the TCA cycle to generate energy. A basic requirement for life is energy, hence the TCA cycle developed quite early in the evolution of life and was passed on to all organisms that are dependent on oxygen for living. It is no more surprising that all animals use the TCA cycle to generate energy than all animals use DNA to pass on genetic information. Boghog (talk) 20:32, 28 October 2011 (UTC)
After more carefully looking into this (see for example PubMed), it appears that components of the TCA cycle were derived from anaerobic bacteria and the TCA cycle itself may have evolved more than once. However there is intense evolutionary pressure to select the most efficient energy producing pathway and the TCA cycle appears to be the most efficient of the possible alternatives (see PubMed). Hence if several alternatives independently evolved, they all rapidly converged on the currently observed TCA cycle. Boghog (talk) 20:54, 28 October 2011 (UTC)
All present day eukaryotes (including all animals and plants) likely arose from a common prokaryote ancestor. Since the TCA cycle was established in prokaryotes before the appearance of the first eukaryote and since the TCA cycle is the most efficient of the alternatives it is not at all surprising that all eukaryotes use the same TCA cycle. An aerobic organism that used a less efficient energy producing process would be at a severe evolutionary disadvantage in comparison to those did and would need to independently evolve the TCA cycle or become extinct. This is the only possible outcome of evolution. Boghog (talk) 09:25, 29 October 2011 (UTC)
Thanks for your answer on another page. But I still think this needs simpler statement early on for novices that can't make it through whole explanation. Student7 (talk) 00:41, 31 October 2011 (UTC)
I am not certain what you are requesting here. Do you want a simple statement in the lead that all animals (and plants and most bacteria) use the same TCA cycle pathway? I think this is already covered in the first sentence ("a series of chemical reactions which is used by all aerobic living organisms to generate energy"). Or in addition, do you want an explanation for why all aerobic organisms use the same pathway? This second question is more complicated and requires an explanation that the TCA cycle is the most efficient out of several alternatives and therefore there is strong evolutionary pressure to select this pathway. I think it is better to address this question in a separate section after the basics of what the TCA cycle is and why it is important is summarized in the lead. Boghog (talk) 21:52, 31 October 2011 (UTC)
The problem is that the statement: "....used by all aerobic living organisms to generate energy." is wrong. first of all aerobic includes living, so thats just an unneccesary repetition, and secondly, but more important. Its not all aerobic organism, its true for all aerobic eukaryotes. but definetly not for all aerobic prokaryotes. — Preceding unsigned comment added by (talk) 16:34, 15 November 2011 (UTC)
What might be redundant here is "living" since it is implied. Aerobic is certainly not redundant since organisms can be classified either as aerobic or anaerobic. Finally, to the best of my knowledge, all aerobic prokaryotic organisms use the same TCA cycle. Can you name a single example of an aerobic prokaryote that does not use the TCA cycle? Boghog (talk) 20:43, 15 November 2011 (UTC)

Aldol addition vs condensation reaction of citrate synthesis[edit]

I've reverted a recent edit by an anon editor claiming that the condensation of oxaloacetate with acetyl-CoA to form citrate is an aldol addition. I think this needs further clarification rather than a hand wave. The majority of the literature (see eg, here here states that it is a (Claisen-type) condensation step. I'm no expert for these types of reactions and perhaps I'm splitting hairs, but this caught my eye, because there seem to be a number of differences between these types of reactions. Malljaja (talk) 17:27, 9 May 2010 (UTC)

Citric Acid[edit]

I don't know anything about the topic, but I searched the page for "citric acid", and I couldn't find any mention about what the citric acid cycle has to do with citric acid. I assume it does, and perhaps I could go to the citric acid page, learn the alternative names, cross-reference, and figure it out. But for the uninitiated, I think it would be useful if there was a mention of it. — Preceding unsigned comment added by (talk) 16:27, 16 September 2011 (UTC)

This is called the citric acid cycle as there a molecule of citric acid that is broken down and then regenerated as the cycle runs. If I get around to some edits I may clarify the introductory sections which do appear to be written for and by biologists or biochemists. Newmanrs (talk) 04:53, 27 October 2011 (UTC)
Thanks for clarifying that. The lead now mentions that citric acid is consumed and regenerated during the course of this cycle. Boghog (talk) 10:34, 29 October 2011 (UTC)
Just think of it as orange juice :) (talk) 03:35, 11 June 2012 (UTC)

Actual yield of ATP[edit]

Is it 38, 2 net of 40? 36, 2 net of 38? Khan Academy says 38, so we'll stick with that? A lot of Uni's are teaching 36, and I'm pretty sure by optimality, that's wrong (talk) 03:35, 11 June 2012 (UTC)

"Actual yield" here, does that imply that that is what happens in vivo, in situ, in the real world? Actually you can have cells like yeast cells that are totally uncoupled --- you get just a few ATP made from that molecule of glucose because ox phos is not generating ATP (although it is running for electron transport.) These "Actual yield" numbers are all theoretical, based on in vitro measurements of what you CAN get from various reactions in the lab. The answer is pretty much just like Abe Lincoln said when asked how long a man's legs should be; President Lincoln answered "Long enough to reach the ground." How many moles of ATP should a cell get from a mole of glucose? Well, enough to satisfy its metabolism at the moment. Richard8081 (talk) 09:44, 30 June 2012 (UTC)
The previous comment mentions yeast cells but isn't supposed to mean that all yeast cells are uncoupled all the time; no no no, it just means that under certain conditions, ie when they are dividing very rapidly and the oxygen tension is right around atmospheric = 20% or so, you'll find that yeast cells in batch culture are uncoupled (ie mitochondria isolated from these cells will be found to be uncoupled).Yeast cells can be all over the map with respect to how many moles of ATP are being actually yielded from a mole of glucose; a good example of the point I'm making here that there's no stoichiometry to this ratio in the real world. Richard8081 (talk) 09:49, 30 June 2012 (UTC)
Assuming the organism has sufficient oxygen, the theoretical maximum yield of ATP through oxidation of one molecule of glucose is 38 (assuming 3 ATP per NADH and 2 ATP per FADH2). In eukaryotes, the two equivalents of NADH generated in the cytoplasm during glycolysis must be transported into the mitochondria consuming two equivalents of ATP reducing the net production of ATP to 36. Furthermore according to PubMed the yield of ATP from NADH and FADH2 is normally less than the theoretical maximum because of inefficiencies in oxidative phosphorylation due to leakage of protons across of the mitochondrial membrane and slippage of ATP synthase / proton pump. The actual yields are closer to ~2.5 ATP per NADH and ~1.5 ATP per FADH2 further reducing the total net production of ATP to approximately 30 (see NBK22448). Boghog (talk) 11:29, 30 June 2012 (UTC)

Okay, you've got your theory down pretty good, with references and a solid recitation of the catechism of How much ATP do you get per glucose molecule? But it's all in vitro and it's all numerology. In vitro! That's what is being pointed out here -- in vitro. The yield of the in vitro reactions from isolated mitochondria does not tell you how much ATP , ie the stoichiometry of ATP production in living cells. But, you can always find some reference that recites that catechism; in fact, you can go into Biochemistry class on the day that that part is being lectured about and they'll go through the addition and come up with 32 or 36 or 38 or whatever but believe me, it's about the same as when they tell you how much horsepower your car engine puts out --- it depends; all the way from zero up to some really big number that your actual car could actually put out if it were at, say, Le Mans. Richard8081 (talk) 14:19, 24 September 2012 (UTC)

Your milage may vary ;-) However since organisms are under intense selective pressure concerning energy efficiency, I would imagine that many organisms achieve close to the practical yield of approximately 30. Boghog (talk) 15:37, 24 September 2012 (UTC)

Precisely --- but your imagination is not what Wikipedia is supposed to be all about. Richard8081 (talk) 16:14, 24 September 2012 (UTC)

It's not really the "imagine" part that's a problem, Einstein himslef lauded imagination in science; it's the word "practical" as in "practical yield". Just change that to "theoretical yield" or "in vitro yield" and I'll be a happy camper. There's nothing real-world about those numbers at all. (and in the real world, as Professor Jasper Rine at Berkeley lectures in the intro bio course, organisms trying to grow as fast as they can eg yeast and bacteria in the pond,use substrate level phosphorylation not oxidative phosphorylation; as the Professor puts it, in the lecture, "When you're going from Berkeley to Sacramento and you have the choice of the Prius or the Porsche, which one do you take? If you're a yeast cell, you take the Porsche, every time." Think about it --- when they start their colony there is plenty of carbon and energy source ie oxidizable substrate; the job is not to conserve it or make the most of it, the job is to burn it as fast as they can (yeast cells even come back later and scavenge what they threw away when there was plenty = diauxic growth). They don't plan for the future; they don't conserve; they make hay while the sun shines. Humans are the same way --- for a hundred years we have burnt as much oil as we can as fast as we can, in the name of progress; and there are hundreds of millions more of us who just can't wait to burn their share. Energy is NOT the limiting factor you --- and the textbook perhaps -- make it out to be. It BECOMES the limiting factor maybe; unless the accumulation of toxics gets there first.Richard8081 (talk) 16:26, 24 September 2012 (UTC)

Evolution is not driven by the average state when food may be plentiful and an organism can be sloppy about extracting energy from food but about extremes when food is scarce and inefficient energy extraction will lead to death and prevent that individual from passing on its genes. Boghog (talk) 20:06, 24 September 2012 (UTC)
One conspicuous exception to the above is thermogenesis where food is converted into heat without generation of ATP. However this is the exception that proves the rule since hypothermia can also lead to death hence there is a strong selective pressure for organisms to develop conditional thermogenic mechanisms. Boghog (talk) 20:37, 24 September 2012 (UTC)

Evolution is driven by the initial state when food is plentiful and an organism can be sloppy about extracting energy from food. When food becomes scarce, that will lead to sporulation or similar strategy to weather hard times, so when the sun shines again that individual and its many brethren and sisters from the time of plenty will pass on their genes.

Conservation's got nothin' to do with it. Richard8081 (talk) 04:33, 7 October 2012 (UTC)

Imagine two species of yeast, the energy efficient Saccharomyces frugalis and an energy inefficient Saccharomyces inpendiosus. In times of plenty S. frugalis has more useful energy availlable for reproduction, and hence will produce more progeny than S. inpendiosus. In times of shortage, S. inpendiosus will be forced to sporulation sooner than S. frugalis. S. frugalis will still be able to reproduce (albeit at a slower rate) where as reproduction of S. inpendiosus will come to a complete halt. Again, S. frugalis will be able to out reproduce S. inpendiosus. Even if plentiful times are more common than times of shortage, It won't take very many generations before S. frugalis takes over and S. inpendiosus becomes extinct. Boghog (talk) 08:54, 7 October 2012 (UTC)
Also please note that S. frugalis and S. inpendiosus are in direct competition for the same resources and as S. frugalis becomes more plentiful it will reduce the available resources for competing species such as S. inpendiosus. "Times of plenty" will become shorter and shorter for S. inpendiosus further accelerating its decline. Boghog (talk) 09:22, 7 October 2012 (UTC)
The earliest organisms from which all life on earth evolved were under strong evolutionary pressure to develop efficient energy utilization. Furthermore energy efficiency is maintained and fined tuned throughout evolutionary history by these same selective pressures. Hence life has become "hard wired" for energy efficiency. Boghog (talk) 09:45, 7 October 2012 (UTC)

Quoting Boghog "Imagine two species of yeast, the energy efficient Saccharomyces frugalis and an energy inefficient Saccharomyces inpendiosus..." Once again: "...your imagination is not what Wikipedia is supposed to be all about."Richard8081 (talk) 02:11, 23 October 2012 (UTC)

This is a talk page, not a Wikipedia article. I was merely trying to explain how evolution works. Do you have any reliable sources to contradict anything that I have stated above? In particular, can you document any cases of energy inefficient life (besides the special cases like thermogenesis)? Boghog (talk) 17:03, 6 November 2012 (UTC)

No prob. How about a guy driving a Buick? Richard8081 (talk) 04:48, 26 November 2012 (UTC)

Buick ≠ life. I asked for a citation, not an analogy. Boghog (talk) 07:23, 26 November 2012 (UTC)
The Pasteur effect in this context is highly relevant. When there is insufficient oxygen, yeast switch from the energy efficient aerobic oxidation (that relies on the citric acid cycle), to energy inefficient anaerobic fermentation. Through a number of feedback mechanism (see PubMed) fermentation is inhibited when there is sufficient oxygen. Hence if yeast has enough oxygen, it will preferentially use the energy efficient route and only resort to energy inefficient fermentation if forced to. Life is far more intelligent that a Buick driver. Boghog (talk) 19:03, 26 November 2012 (UTC)

The example of a guy driving a Buick is not an analogy; and does not require a citation. It's reality. It's life. Life is profligate of energy. That's just the way life is. Life takes the Porsche, not the Prius. And please, please be careful about invoking this "intelligent" stuff; the Court already ruled on that (in Pennsylvania a few years back.)Richard8081 (talk) 16:17, 6 December 2012 (UTC)

Equating life with a Buick is an analogy. A citation is required to document the extradorinary claim that given a choice, life prefers inefficient energy expenditure. Life uses energy, but is very efficient on how it does so in order to maximize the chances of passing on genes. This is how life works. Boghog (talk) 16:48, 6 December 2012 (UTC)
I think it makes a lot of sense to add text as suggested by Boghog above: "Assuming the organism has sufficient oxygen, the theoretical maximum...", however, tell that this is all in vitro and explain why the situation in vivo is different. My very best wishes (talk) 17:52, 6 December 2012 (UTC)
"explain why the situation in vivo is different". This is exactly where we need a citation. In terms of energy efficiency, there is no significant difference. If you disagree, please find a reliable source to document the difference. Boghog (talk) 18:58, 6 December 2012 (UTC)
All right. If there is no citation that situation in vivo is different, I suggest just to include text you proposed above without mentioning "in vitro" or "in vivo". If someone finds RS about in vivo later, than he can modify this later accordingly. My very best wishes (talk) 19:35, 6 December 2012 (UTC)
For a relevant citation that discusses the efficiency of the mitochondrial respiratory chain see PubMed. The efficiency can be less than the theoretical maximum, not because life some how takes enjoyment in wasting energy, but rather for specific purposes such as reducing reactive oxygen species, thermogenesis, and metabolic regulation. Boghog (talk) 21:26, 8 December 2012 (UTC)
Good change, but it is a little misleading. If I understand correctly, most of the ATP is produced during the oxidative phosphorylation, which not a part of the cycle. This should probably be clarified. My very best wishes (talk) 22:58, 8 December 2012 (UTC)
The first sentence of the new efficiency section states "... yield of ATP through oxidation of one molecule of glucose in glycolysis, citric acid cycle, and oxidative phosphorylation is ..." which I think it is pretty clear. Boghog (talk) 10:25, 9 December 2012 (UTC)

Wow --- I havent' looked at the article, maybe something changed, but the PubMed reference you've dug up there is GREAT! It proves the point beautifully that when you somehow manage to measure the yield of ATP, you get goofy numbers like 1.4 as the P/O ratio; and that it's all over the map, depending on what else is going on with the local environment, like the temperature or the oxygen availability, and maybe th phase of the moon :-)) Good work! I"m done. We're done. The "Yield of ATP" is, well, whatever it is. (really, come on, didn't you ever wonder a little about how come the ATP/O = P/O ratios in the literature are NEVER integral? But these numbers that are bandied about in Discussions are always nicely integral? Kuhn comes to mind.) — Preceding unsigned comment added by Richard8081 (talkcontribs) 03:12, 9 December 2012 (UTC)

Just one note before I go though --- "If I understand correctly, most of the ATP is produced during the oxidative phosphorylation, which not a part of the cycle. This should probably be clarified." was noted by User:My very best wishes; which indicates that Wishes does NOT understand correctly. The ATP referred to, what he refers to as "Most of the ATP" being discussed here, this theoretical 38 ATP per glucose, is an in vitro maximum yield of ATP based on massaging isolated mitochondria in a reaction chamber. That big number of 38 is very much dependent on the ASSUMPTION that oxidative phosphorylation runs full blast. In vivo, it doesn't. Boghog's reference on PubMed says so. There never was any reason to think that the relationship of ATP-produced to oxygen-consumed was integral, or even stoichiometric; so there's no reason to toss any fudge factors like peroxide production or thermogenesis into the mix of reasons why the mitochondria's electron flow apparatus is not integral or stoichiometric. Actually, it's infinitely variable, more like an electronic device, which is what it is. okay, ten four. Richard8081 (talk) 00:19, 10 December 2012 (UTC)

Please don't mistake silence for agreement. The above contains some serious misrepresentations that should be corrected, but this extended discussion demonstrates that further dialogue is futile. Boghog (talk) 21:09, 21 December 2012 (UTC)

"Serious misrepresentations"? Serious misrepresentations? Listen up: When you can show me a table or graph --- any in vivo results; not theory, or calculations, but measured results, in a journal article --- that show anything remotely resembling 30+ moles of ATP being synthesized per mole of glucose, you let me know. Don't just cite all the different sources that repeat the same catechism over and over; find some RESULTS that back up those numbers. What's in the article about 36 or 38 or whatever, that's a misrepresentation. (I might say "serious misrepresentation but that's pretty strong talk.)Richard8081 (talk) 15:17, 3 January 2013 (UTC)

The theoretical maximum is 36 moles of ATP per mole of glucose. Because biological systems are not 100% efficient, the actual in vivo yield as stated above is ~30.
Here are some RESULTS (with error bars) that back up those numbers: According to PubMed, "The absolute values of the [experimentally determined] thermodynamic efficiency are similar to the [canoncial] result (~50%) calculated by Lehninger of the generation of ATP from glucose using a totally different methodology." There are some differences between liver, heart, and brain. In liver the yield is optimzed for efficiency while in heart, the yield is optimized for maximal ATP output. But even in the heart (see figure 3 in the citation), the process is only ~10% less efficient (yield = ~27 moles of ATP/mole of glucose). Boghog (talk) 22:21, 3 January 2013 (UTC)
"What's in the article about 36 or 38 or whatever, that's a misrepresentation" – please carefully reread what is written in the article. It says in eukaryotes the theoretical yield is 36 while the observed yield is ~30. Boghog (talk) 22:30, 3 January 2013 (UTC)
Just to be absolutely clear, life never achieves > 30 moles of ATP / mole glucose oxidized. This yield is the practical limit of what is achievable using biological machinery constructed from proteins and phospholipid bilayers. At the same time, except for well defined exceptions already mentioned above, life always achieves close to the practical limit of 30 moles of ATP. ATP yields are not all over the place. They are tightly constrained by evolutionary selection. In cases where the yields are lower, this is done for specific reasons that enhance the evolutionary competitiveness of the organism. Boghog (talk) 07:37, 5 January 2013 (UTC)

The PubMed citation is all about isolated mitochondria , ie in vitro research, nothing in vivo. Here's a quote from it: "The purposes of the series of studies in mitochondria isolated from liver, heart, and brain were as follows:" See that word "isolated"? Okay. Isolated mitochondria = in vitro. There's nothing wrong with in vitro studies, far from it, that's how we find stuff out; but don't extrapolate to pronouncements about "life"; it's a misrepresentation.Richard8081 (talk) 05:43, 7 January 2013 (UTC)

Repeating what I already said above:
  • "explain why the situation in vivo is different". This is exactly where we need a citation. In terms of energy efficiency, there is no significant difference between isolated mitochondria and mitrochondria in cells. Why would there be? If you disagree, please find a reliable source to document the difference.
Boghog (talk) 06:43, 7 January 2013 (UTC)
See PMC 3070485 for a paper that reviews methods for measuring in mitochondrial efficiency in vivo and in vitro. The most relevant section is section #4 (mitochondrial coupling). This paper in turn cites PMC 1766336. The second paper shows that mitochondrial electron transport is midly uncoupled from ATP production in muscle reducing the energy efficiency of this process, but this is done for the specific reason of reducing the production of damaging reactive oxygen species. An exception that again proves the rule. Boghog (talk) 14:43, 7 January 2013 (UTC)

"In terms of energy efficiency, there is no significant difference between isolated mitochondria and mitrochondria in cells. Why would there be? " Definitely let that be the last word on the subject. Richard8081 (talk) 20:20, 9 January 2013 (UTC)

You have not provided a shread of evidence that there is a difference nor any compelling reason why there would be. Unless you can provide a reliable source that documents this difference, this is the last word. Boghog (talk) 20:50, 9 January 2013 (UTC)

And that, amazingly enough, turned out to be, indeed, the last word --- some guy stating his unwavering belief that in vitro and in vivo are all the same to him. RIP. Richard8081 (talk) 05:35, 2 October 2013 (UTC)

Of course in vitro and in vivo often differ, but you want to state that the citric acid cycle energy efficiency is less when measured in vivo compared to in vitro, you must supply a reliable source that documents that difference. In short, prove it. Per WP:V, this is the way Wikipedia works. Boghog (talk) 06:32, 2 October 2013 (UTC)

Richard, I do believe you misrepresented Boghog's words in several places here. Perhaps it would be best to let this argument drop. (Have I just re-ignited it? Sorry.) We don't have to provide sources for something that is not discussed in the article. Is there an actual claim in the article equating in vitro with in vivo? Or is it just a case of the 36/38 ATP number being given, as is standard in biology textbooks? As long as we're clear about what that number means, there is no point for debate. (talk) 21:47, 22 February 2014 (UTC)

Let's let it go at this: The last word on the subject from the one guy was "In terms of energy efficiency, there is no significant difference between isolated mitochondria and mitrochondria in cells. Why would there be? " while the last word on the subject from the other guy is, "Show me some numbers; and if you got no numbers, just tell everybody that the article is referring to in vitro numbers";

and let it go at THAT.  

Richard8081 (talk) 04:23, 24 June 2014 (UTC)


I see that this article is only graded 'C'. A most impressive piece of work in my humble opinion - a credit to all the contributors. Rosser Gruffydd 07:30, 2 October 2012 (UTC)

Why is the history of its discovery not even mentioned?[edit]

It was discovered in 1937 at the University of Sheffield in 1937 by Hans Adolf Krebs (see Hans Adolf Krebs). — Preceding unsigned comment added by Jono2013 (talkcontribs) 21:11, 24 April 2013 (UTC)

It is mentioned in the last paragraph of the lead "the components and reactions of the citric acid cycle were established in the 1930s by seminal work from the Nobel laureates Albert Szent-Györgyi[4] and Hans Adolf Krebs.[5]". Boghog (talk) 21:18, 24 April 2013 (UTC)
I do not think that sentence is precise or accurate enough for an encyclopedia. The CYCLE was identified ONLY by Krebs. Before that, it was simply a bunch of non connected pathways. Krebs' Nobel prize in 1953 was explicitly and precisely for his "discovery of the citric acid cycle." Moreover to place Szent-Györgyi before Krebs is not correct either, if this page is about the TCA Cycle rather than simply Fumaric acid. Jono2013 (talk) 12:02, 25 April 2013 (UTC)
Albert Szent-Györgyi laid some of the important ground work with out which it would not have been possible to discover the cycle. The metaphor standing on the shoulders of giants is especially relevant in this context. Boghog (talk) 12:21, 25 April 2013 (UTC)
Hans Adolf Krebs himself acknowledges the important contributions of Szent-Györgyi:
Boghog (talk) 13:19, 25 April 2013 (UTC)
You have not addressed my contentions. Moreover, you are adding pejorative opinion re your "standing on heads" which is not supported by facts. It is also deeply disrespectful to Krebs. It is what it is. There is no support for your perjorative contention (and I assume it is you who has inserted the erroneous additional name) or your posture. And of course Krebs recognized Szent-Györgyi - as is normal in strict academic rigour. But that is entirely separate to claiming Szent-Györgyi discovered the TCA cycle which I am keen to ensure is not implied for one moment as it would be wholly inaccurate -let alone presumptive of you in the least to recast matters which even hinted at the same. You have no basis whatsoever Jono2013 (talk) 14:10, 25 April 2013 (UTC)

──────────────────────────────────────────────────────────────────────────────────────────────────── A couple of points:

  • Please keep in mind WP:AGF. Comment on the edits and not the editors.
  • The metaphor standing on the shoulders of giants is not pejorative. Quite to the contrary, this metaphor is deeply respectful to both Krebs and Szent-Györgyi and is strongly supported by the facts. The fact is that Szent-Györgyi laid much of the ground work for elucidation of the Kreb cycle (see quotation in the next section below).
  • "and I assume it is you who has inserted the erroneous additional name" – That assumption is wrong (diff). Again, assume good faith. Boghog (talk) 14:46, 25 April 2013 (UTC)
Please do not hide behind matters of form when you have behaved in a manner which is unsupported. The metaphor "standing on the shoulders of giants" is inapposite and can be implied (as surely you can countenance) that Szent-Györgyi was the "giant" and therefore Krebs was (by comparison) relatively a "mere nothing". I'll take the Pepsi challenge on that one. And no, I am not interesting in implying "good faith" or "bad faith" when a position is so ostensibly skewed or biased in fact. Intention is irrelevant in such respects. All I wanted to ascertain was the basis IN FACT for your unsupported bias. Not denigrate your mens rea. I have no interest in your intention save to the extent you depart from cold objective analysis, which you have done, for reasons which still are not forthcoming. I hope that is clear.
Jono2013 (talk) 15:17, 25 April 2013 (UTC)
Again, please comment on the edits and not the editors. It is clear both Krebs and Szent-Györgyi are giants and both made contributions to the discovery of the cycle. Hence the metaphor is highly relevant to the describe the discovery. Finally I have no ulterior motives other than giving credit where credit is due. Boghog (talk) 15:31, 25 April 2013 (UTC)
You have no right to be so presumptive. Wiki is NOT a fountain of original thought. See my comments in the section immediately below. There is NO basis for your position. And I am attacking your position, not you. But I really dont care too much how you interpret that as you seem to be your own master in such respects
Jono2013 (talk) 15:41, 25 April 2013 (UTC)
By the way, just so we are clear, the user who caused the change so as to wrongly insert the Szent-Györgyi name into the Krebs/TCA/Citric Acid Cycle is HUNGARIAN. A pure case of national bias and vandalism. Plain and simple. And yet you persit.
Jono2013 (talk) 15:57, 25 April 2013 (UTC)

Further, on this point, the user's justification for the grotesque renaming is stated as follows
"11:38, 17 June 2007 (+34)‎ m Citric acid cycle ‎ (Szent-Györgyi Albert also earned the Nobel p. in 1937 for this.)"
You'll note it is not only factually inaccurate but moreover to ensure the "shoe-in" of the required subterfuge, is marked as a "minor" edit. Clearly this user has no biochemistry background. No one who studied Biochem could make such a change to one of the most pivotal metabolic pathways and classify it as "Minor". And this is what concerns me with Wiki. The user's page is here ( He seems more of an expert on Hungarian history, which is no doubt the capital fund of his palpable bias.
Jono2013 (talk) 16:39, 25 April 2013 (UTC)

Too many names[edit]

I studied medicine at University and that included Biochemistry and Physiology. We called it the Citric Acid, the TCA cycle or the Krebs cycle. But never the "Szent-Györgyi–Krebs cycle". Moreover, Szent-Györgyi did not discover the cycle per se, he identified fumaric acid and several steps (for which he won the Nobel Prize in 1937. It is Krebs who identified the process as a cycle. — Preceding unsigned comment added by Jono2013 (talkcontribs) 21:17, 24 April 2013 (UTC)

Nevertheless, it is sometimes referred to as the "Szent-Györgyi–Krebs cycle" in the scientific literature. Boghog (talk) 21:20, 24 April 2013 (UTC)
Im afraid you're wrong. It is not. Moreover the "Szent-Györgyi cycle" is ONLY a component of the TCA, as referred to by Krebs himself in his published paper of 1940 (see, "The citric acid cycle and the Szent-Györgyi cycle in pigeon breast muscle" So I'd like you to back-up your assertion, because again this is an encyclopedia and therefore precision is essential - not a "convenient" re-write of history. And I really do not see how passing on a largely unsupported re-name is relevant or justifiable simply because by cause of some "accident" or lack of precision elsewhere, what is and always will be the TCA/Citric Acid/Krebs cycle, shall henceforth be transmogrified into yet another name that it does not need and never has had, save for imprecision and happenstance - the very anathema of what an encyclopedia is supposed to comprise. Jono2013 (talk) 12:14, 25 April 2013 (UTC)
If a reliable source has used a phrase, then that is sufficient reason to include it in a Wikipedia article. Here is a reliable source:
And here is a more complete description of the history:
"The Albert Szent-Gyorgyi Papers: Szeged, 1931-1947: Vitamin C, Muscles, and WWII". Profiles in Science. U.S. National Library of Medicine. :
  • By 1937, Szent-Györgyi had identified the process as a cycle and was close to elaborating all of the steps that generate adenosine triphosphate (ATP), the energy-carrying molecule in all living cells. As it turned out, Szent-Györgyi's focus on malate and oxaloacetate was an error, and Hans Krebs soon found that the key link was citric acid. Thus "Szent-Györgyi's cycle" became the citric acid cycle or Krebs cycle; Krebs, who won a Nobel prize in 1953 for the work, later called it the tricarboxylic acid cycle.
Boghog (talk) 13:18, 25 April 2013 (UTC)
Let's get right to the HEART of this. First, your contention is not supported by provable fact. I sent you the reference to the 1940 Kreb's paper ----- which CLEARLY differentiates between the Szent-Györgyi cycle as against the TCA cycle. How much more "straight between the eyes" do you need things spelled out? It was written by Krebs himself for goodness sake. And you talk of "standing on the shoulder of giants" to disparage Krebs??? What do you think you're doing????
Second, your first source ( MetaCyc) is NOT a primary source. Whereas the 1940 Krebs paper is: moreover the 1940 Krebs' paper is contemporaneous OF THE TIME PERIOD WHEN THE DISCOVERY WAS MADE.
Secondary sources are generally preferred over primary (see WP:PSTS and WP:SCIRS). Boghog (talk) 15:06, 25 April 2013 (UTC)
Third, your second source does NOT support your position. Rather, it is CONFIRMATION of what I have stated all along - namely the Szent-Györgyi cycle and the TCA Cycle ARE NOT the same thing. The Szent-Györgyi cycle is a COMPONENT of the TCA. The sentence "Thus 'Szent-Györgyi's cycle' became the citric acid cycle or Krebs cycle; Krebs, who won a Nobel prize in 1953 for the work, later called it the tricarboxylic acid cycle" confirms this. Your error is not appreciating that the word "became" in the stated sentence means "was modified into". That does not support (and there is NO evidence to state otherwise) that the TCA Cycle term was merely a "name badge" change. That is utterly utterly wrong.
What you choose to call the TCA cycle in the dead of the night is your business. What your not entitled to do is take unprincipled positions, fail to substantively justify matters, ignore primary contemporaneous journal entries, substitute third party opinion, and then, to add insult to injury neatly surmise matters using pejorative metaphors. You have no qualifications or basis to do so - and yet you talk of "standing on the shoulders of giants". To me, not only is that deeply hypocritical of you but moreover, it shows a resistance towards the admitting of an error. And that concerns me. Because this is an encyclopedia. And I as stated above, imprecision and happenstance is the very anathema of what an encyclopedia is supposed to comprise. Yet you persist. Despite the University of Sheffield being clear on the point, and despite the Nobel Committee of 1953 being very clear and precise. But you know better? Or should I say, a third party webpage and your interpretation of the word "became" knows better?
Jono2013 (talk) 14:31, 25 April 2013 (UTC)
Calm down. How does acknowledging Szent-Györgyi contribution to the discovery of the TCA cycle diminish Krebs contribution? I think it would be appropriate to include a history section in this article to make clearer the contributions of Krebs and Szent-Györgyi as well as a few others (e.g., T. Thunberg and F. Batelli and L.S. Stern). The way science works is building on previous results (standing on the shoulders of giants). And just to be clear, Krebs himself is clearly a giant. Boghog (talk) 15:00, 25 April 2013 (UTC)
I am quite clear of my facts. I was lectured by Professor R.E.S. Prout of Sheffield University, who wrote in 1965 "Studies on renal transport of citrate using 14C-citrate" Cohen, R. D., and R. E. S. Prout, Clin. Sci. 28: 487–497. So I was lectured by someone who was at the centre of it all. So I really dont want to debate this anymore. And please quit using the "standing on the shoulder of giants" metaphor when it comes to scientific research. It is just inapposite.
Whence, acknowledging contributions made is of course legitimate. Adding a new name where none is needed, nor supported is just flat wrong. Especially when recasts history, and ignores the cold hard facts of the day. I do not have to labor this. Coming up with new "contrivances" destroys the credibility of Wikipedia. It is NOT a fountain of original thought. It is an encyclopedia. You want to go write a paper suggesting yet another name for the TCA cycle, be my guest. But make sure you have it peer-reviewed by real experts and published by a credible publisher. Send it to the head of Biochemistry at the University of Sheffield for good measure, and copying also the Royal Academy in London and the Chairman of the Nobel Prize Committee in Stockholm for additional good measure too. Good luck with your attempt to cause such a massive ground-shift. Until then, there is no room for enlarging or recasting history in the pages of a (mere) encyclopedia. I still dont think you understand the enormity of what you are supporting here. It's grotesque. And that worries me. for the sake of Wiki's integrity.
Jono2013 (talk) 15:37, 25 April 2013 (UTC)
  • "It's grotesque." – Mountain, mole hill ...
  • "And please quit using the "standing on the shoulder of giants" metaphor when it comes to scientific research. It is just inapposite." – The use of this metaphor in the field of science is long standing and distinguished. For example:

    If I have seen a little further it is by standing on the shoulders of Giants

    — Sir Isaac Newton
Why don't we instead concentrate on improving this article instead of having long fruitless discussions? Boghog (talk) 15:54, 25 April 2013 (UTC)
By the way, just so we are clear, the user who caused the change so as to WRONGLY insert the Szent-Györgyi name into the Krebs/TCA/Citric Acid Cycle is HUNGARIAN. A pure case of national bias and vandalism. Plain and simple. And yet you persist.
Jono2013 (talk) 15:58, 25 April 2013 (UTC)
This article needs to have a history section where the contributions to the discovery can accurately be stated. And yes, a Hungarian editor could be biased but please don't confuse what is perhaps a little over zealous national pride with vandalism. Boghog (talk) 16:10, 25 April 2013 (UTC)

Ive stated that you have my full support for such a history section. The issue now is removing that grotesque name change. A act of vandalism has been discovered - for all the reasons stated. So are you going to change it, or do I? I have no problem supporting you on that change and you can even take credit for it. It you are the purist I hope you are, I am quite happy to be magnanimous in such respects. But it must be changed. There is no debating that. Unless you have a bad case of misplaced Hungarian nationalism too.
Jono2013 (talk) 16:15, 25 April 2013 (UTC)

Further, on this point, the user's justification for the grotesque renaming is stated as follows
"11:38, 17 June 2007 (+34)‎ m Citric acid cycle ‎ (Szent-Györgyi Albert also earned the Nobel p. in 1937 for this.)"
You'll note it is not only factually inaccurate but moreover to ensure the "shoe-in" of the required subterfuge, is marked as a "minor" edit. Clearly this user has no biochemistry background. No one who studied Biochem could make such a change to one of the most pivotal metabolic pathways and classify it as "Minor". And this is what concerns me with Wiki. The user's page is here ( He seems more of an expert on Hungarian history, which is no doubt the capital fund of his palpable bias.
Jono2013 (talk) 16:38, 25 April 2013 (UTC)
Let us write the history section and drop the rest of this off topic discussion. Discussing editors motives is irrelevant. What is relevant is article content. Boghog (talk) 17:48, 25 April 2013 (UTC)

You are again risking being perceived as high-handed. I do NOT understand how you can state that serious grounds to reasonably doubt the bona fide intention of a user, who has caused an egregious act of vandalism, is "irrelevant". My subject was the name. I am not going to be deflected by a side-bar about a history section. You can choose to discount the obvious if you wish, but in so doing, this will be at the cost of objectivity. You are ignoring hard historical fact in favor of changing the name of one of the most important metabolic cycles ---- made by a user who is at most a specialist on anything but biochemistry, and whose justification is clearly bogus. Your resistance is so concerning to me that I feel constrained to ask: Are you Hungarian? And I ask for the purest of reasons because nationalistic bias has no place in an encyclopedia let alone in a purely scientific entry. It completely countermands Wiki's integrity and reliability, as Im sure you'll agree.
Jono2013 (talk) 18:25, 25 April 2013 (UTC)
If you must know, my ancestry is overwhelmingly German without, as far as I know, a trace of Hungarian. So if nationality were an issue, I would tend to be biased towards Krebs. I do note that you attended Sheffield University where Krebs made his discovery, so if anyone has a possible bias, it is you and not I. I agree to the changes to the article that you made. The rest of this discussion especially concerning editor motives is irrelevant and really needs to stop. Boghog (talk) 19:36, 25 April 2013 (UTC)
I am not biased in favor of one of my alma maters. Rather, the facts - and only the facts - speak for themselves. My other is the University of Cambridge (where I was appointed a professor at the age of 42), so that should make me biased against Krebs on the basis he moved on from Sheffield to Oxford. In other words, when do pointless allegations cease? You know very well that my points were perfectly formed and made, and that the erroneous inclusion was made for highly dubious reasons at best. And the question re your nationality (rather than ancestry) was perfectly proper in the given circumstances.
And just to be clear, I had to learn every single aspect of the cycle off-by-heart during my undergraduate days. It was compulsory, as it is THAT fundamental. And to trifle with its name, when there is no basis for it, so as to distort matters for self-perceived nationalistic gain, is sheer vandalism. Nothing less. I am sure that Szent-Györgyi, if he was half the scientist as I am sure he was, would have been appalled. And highly embarrassed too, that some self-appointed Hungarian history "dweeb" distorted matters so, for the World to see.
Jono2013 (talk) 20:38, 25 April 2013 (UTC)
Concerning editor motives: "... when do pointless allegations cease?" This is exactly the point I was trying to make. Boghog (talk) 21:00, 25 April 2013 (UTC)

Bear in mind that ol' Boghog here was the one who said, supra,

"In terms of energy efficiency, there is no significant difference between isolated mitochondria and mitochondria in cells. Why would there be?" You might as well be debating with a sofa.

Richard8081 (talk) 05:38, 26 June 2013 (UTC)

Also bear in mind that I also said above, If you disagree, please find a reliable source to document the difference. Statements in Wikipedia (and debates on talk pages) need to backed up by reliable sources. Boghog (talk) 06:36, 26 June 2013 (UTC)
I just stumbled on this exchange about half a year after it took place, but here are my two cents: Boghog, while I think Jono perhaps got too animated in the debate, he has proved his point beyond any doubt. Your sources were not appropriate, for the reasons he explained. And although editors are not supposed to use personal knowledge as evidence of anything on Wikipedia, I will say that from my own experience as a biologist, the "Szent-Györgyi cycle" is not a credible name for the Krebs cycle. Thus I would need to see some pretty strong evidence to the contrary before I considered your argument to have merit. The burden of proof is always on the person making the claim that is contrary to the common understanding. (talk) 21:33, 22 February 2014 (UTC)
I think you missed the point of much of the above discussion. I know the discussion was quite long, but please note one critical statement that I made above:

I agree to the changes to the article that you made. The rest of this discussion especially concerning editor motives is irrelevant and really needs to stop.
— User:Boghog 14:36, 2 March 2014 (UTC)

I was not so much objecting to what Jono was saying, but how it was said. In short, comments on talk pages should be confined to the edits not the editors. Attacking other editors is not an effective means of persuasion. Furthermore the sources I supplied were appropriate. The disagreement came in the interpretation of those sources. While I will admit that using the term "Szent-Györgyi–Krebs cycle" to describe the citric acid cycle is controversial, there is some justification for the term in that Szent-Györgyi made important discoveries that laid the ground work for the discovery of the cycle. Boghog (talk) 14:36, 2 March 2014 (UTC)

I can chemdraw the molecules[edit]

I can chemdraw the molecules in the citric acid cycle, much like how the glycolysis is setup. I have no idea how to use wikipedia however, and need help implementing the nice layout like in glycolysis. I believe chemdraw can export to .svg, so that should be fine.

For the person asking what's so important about the citric acid cycle. It's because the cycle generates an abundant amount of NADH and FADH2. These two compounds help create ATP much more readily than simple glycolysis. Voet&Voet Biochem book says glycolysis makes 2 net ATP per run. For all the NADH's and FADH2's created by the citric acid cycle, if they were all used to create ATP (so 6 NADH and 2 FADH2 consumed entirely), the net yield would be 17 ATP, an 8.5 timefold more than 2. (talk) 20:27, 1 February 2014 (UTC)UCSD student in metabolism class

adding .gif image[edit]

I am just an undergraduate student and I frequently visit the page of krebs cycle. I was thinking it would be just great if someone would .gif images in pages regarding krebs cycle and other pages like it. It would be great to view those steps in .gif . I am not working in it but would be great to know if someone is working in it. Or let me know if it is useless idea to work upon. Learnerktm (talk) 06:09, 13 October 2014 (UTC)

rate-limiting step(s)[edit]

One rate-limiting step is now mentioned, but without much explanation. When clicking that hyperlink "Oxalosuccinic acid/Oxalosuccinate is an unstable 6-Carbon intermediate in the TriCarboxylic Acid Cycle". No references behind that link! Can one supplement something to remove the rate limit and what might be theoretical or actual benefits or drawbacks? Here is one supplement database: which is a bit like wikipedia, but some medical advice is allowed there, unlike in Wikipedia. ee1518 (talk) 09:08, 18 April 2015 (UTC)