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I understand that muscles do anaerobic metabolism, specifically, "lactic acid fermentation", which I understand produces lactate. I'm not asking about that process.

What chemical conversions are involved , and what's the name for the process, when the muscles use lactate as an energy source?

I'm aware that it can happen as This paper, is tellingly and usefully titled, "Lactate as a fuel for mitochondrial respiration" (though I only have the abstract)

And aside from that paper i've also heard

"lactate produced during exercise can be reused as fuel by the muscles by turning it into glucose".

But I'm interested in what chemical conversions are involved

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  • $\begingroup$ Have you read about Cori's cycle? Not sure if it answers your question, but it is relevant to lactate transport and clearance. $\endgroup$ – Satwik Pasani Jul 5 '17 at 9:56
  • $\begingroup$ @SatwikPasani You can post that as an answer and i'll add my elaboration as an end note. And if it's wrong hopefully somebody will comment or post a better answer.. actually just needs a formula but should be easier to find now.. $\endgroup$ – barlop Jul 5 '17 at 10:05
  • $\begingroup$ @SatwikPasani thanks. My elaboration Looking at en.wikipedia.org/wiki/Cori_cycle shows en.wikipedia.org/wiki/Gluconeogenesis it looks like Gluconeogenesis in the liver converts lactate to glucose. So the muscles wouldn't be fuelled by lactate(the article was unclear to suggest so). Muscles are fuelled by Glucose (not lactate) and they'd do aerobic and anaerobic metabolism.. I'm not expert though but that seems correct. But now I see more where lactate fits in.. The liver takes it in and converts it to glucose which can go back into the muscle. $\endgroup$ – barlop Jul 5 '17 at 10:09
  • $\begingroup$ Just mended the broken link. $\endgroup$ – David Jul 5 '17 at 12:40
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    $\begingroup$ @David i'm curious.. I get curious sometimes. $\endgroup$ – barlop Jul 6 '17 at 10:48
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I see you've already got an answer in the comments, so this is rather a collection (with more proper formulation) of comments. As is known, lactate is produced by muscles (generally) during exercise due to absence of oxygen. However, the lactate produced can be used again in following two ways:

  • Conversion of lactate to glucose in the liver via a process known as Cori's cycle. Basically, the lactate produced from the muscles is released into the bloodstream, through which it reaches liver. There, it is converted back to glucose and again released into the bloodstream, through which muscles can use it again as fuel. The basic cycle looks like:

    Cori's cycle

  • Conversion of lactate to pyruvate is the one you are concerned about. However, this process does not have a special name, because this reaction can be catalyzed both in forward and reverse direction. In the absence of oxygen, an enzyme lactate dehydrogenase convertes pyruvate into lactate, consuming 2 H+ during the process. However, when the envrionment is rich in oxygen, or the concentration of lactate is high, the same enzyme converts lactate into pyruvate, producing 2 H+ in the process. The reaction can be shown as: $$\ce{CH_3COCOO^- + NADH + H^+ \leftrightharpoons CH_3CH(OH)COO^- + NAD^+}$$

    Thus, when the concentration of lactate increases, the enzyme lactate dehydrogenase catalyzes the (above) reaction in the reverse direction. After this, the pyruvate produced can be used in the TCA cycle.

PS: there have been studies which now suggest that indeed lactate, not glucose, is the primary energy source of neurons. As per the lactate-shuttle hypothesis, the glial cells neighboruing neurons convert glucose into lactate, which is then used by the neurons. This fits with the observation that the extracellular fluid immediately surrounding the neurons is richer in lactate as compared with blood and cerebrospinal fluid, as shown in microdialysis studies. These studies suggest that glucose is not the actual primary energy source of neurons.

EDIT: As you see, the first reaction in both the cases is $\ce{lactate \rightarrow pyruvate}$. However, the main difference arises after this reaction. In muscle cells, this pyruvate is used in Krebs cycle, for which the first enzyme is pyruvate dehydrogenase converting pyruvate to acetyl-coA. However, in gluconeogenesis i.e. formation of new glucose molecule (a part of Cori's cycle), the first step is conversion of pyruvate to oxaloacetate, and is catalyzed by the enzyme pyruvate carboxylase. Thus, although the first step in both processes is the same, the end product is quite different.

References:

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  • $\begingroup$ Thanks. What's your view re what david says about that paper, which is that it's saying that the formula he gave "Lactate -> Pyruvate -> AcetylCoA." is according to that paper, a reaction that happens in the muscle itself $\endgroup$ – barlop Jul 5 '17 at 17:31
  • $\begingroup$ according to that cori cycle image you've given, which i've seen verified elsewhere too.. it's as you say, lactate to pyruvate to glucose.. in the liver. So why do you say "lactate to glucose" as one point, and "conversion of lactate to pyruvate" as a separate point.. Isn't lactate to pyruvate just half of that "pyruvate to glucose" reaction.. Also, why do you think that "lactate to pyruvate" is more relevant than "pyruvate to glucose"? $\endgroup$ – barlop Jul 5 '17 at 17:38
  • $\begingroup$ So there's 3 words here then.. Lactate->Glucose is Gluconeogenesis. So what's the word for the in between reactions of A)Lactate to Pyruvate (the reverse of lactic acid fermentation) and B)Pyruvate to glucose(the reverse of Glycolysis). (And yeah I understand your image I see the reverse reactions occur in the liver). $\endgroup$ – barlop Jul 5 '17 at 18:09
  • $\begingroup$ Secondly, David wrote in one comment "the answer is Lactate -> Pyruvate -> AcetylCoA " and another "The reference you cite says it takes place in the muscle. There is no distinct name for the — as people didn't think it occured there was no reason to name it. " <-- So am I interpreting David's comment correctly there, that he's saying that that process with that formula occurs in the muscle? And that it's according to that recent study and thus being a recent discovery it has no name. $\endgroup$ – barlop Jul 5 '17 at 18:11
  • $\begingroup$ (note, also I think David isn't talking about the Cori cycle, and the liver eg he said it occurs in the muscle, and he thought that one commenter was "not reading the question or the paper in taking about the Cori cycle" ). I think the Cori cycle is relevant but it's also relevant that there may be this other scenario that David brings up of a process with that formula David gave, occurring purely in the muscle, not the liver. $\endgroup$ – barlop Jul 5 '17 at 18:13
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Thanks David And Homosapien..

HomoSapien has posted an answer which i've accepted.

I have included here a useful diagram showing the conversion of Lactate to Pyruvate to AcetylCoA, and a description how it relates to the question.

As has been mentioned there are two different processes not to be confused. There's the Cori Cycle aka Lactic Acid Cycle, where which involves the liver, blood and muscle. Liver converting Lactate->Pyruvate->Glucose (that process in the liver is called Gluconeogenesis). Glucose travels to the muscle.. Muscle performs Glucose->Pyruvate->Lactate , lactate travels to the liver and in that cycle. so there Lactate is very indirectly fuelling an anaerobic metabolism in the muscle. Also note that(I understand from speaking to a biochemist), that when the Pyruvate is converted into Glucose it's technically not the reverse of Glycolysis since different enzymes are used and it's a different pathway. I see that the conversion of pyruvate to lactate is a reverse of lactic acid fermentation, as the same enzyme, LDH, is used

The other process, which is quite interesting and less spoken about in popular articles, is one which occurs entirely within the muscle. It's what David explained was Lactate -> Pyruvate -> AcetylCoA There is no conversion to Glucose there. And as Bryan has pointed out to me, The lactate metabolism they are talking about in that paper isn't really anything special - all of the reactions except lactate->pyruvate, are exactly the same reactions from standard glucose aerobic metabolism. That - Lactate->Pyruvate->Acetyl Coa is the one the paper is talking about. A main point to make there is that the Lactate->Pyruvate conversion is performed by the enzyme LDH which can work both ways, and in doing lactate->pyruvate, it is doing the reverse of "lactic acid fermentation". The other part, Pyruvate->AcetylCoA is what happens in aerobic metabolism.

I found a really good picture in that paper which helps explain things related to the answer of my question in regards to the process where muscle converts lactate to pyruvate as fuel for aerobic respiration... (I suppose it could potentially fuel anaerobic metabolism rather than aerobic)

So the picture shows the cell and the mitochondria within it.

enter image description here

The paper itself is titled "Lactate as a fuel for mitochondrial respiration"

We see in that picture the Glycogen which will be converted into Glucose, is converted into Pyruvate (Glycolysis), and some Pyruvate is converted into Lactate by LDH (Lactic Acid Fermentation). But some Pyruvate can be fed into the Mitochondria which would fuel mitochondrial respiration. The way that Lactate would fuel mitochrondrial respiration, would be lactate converted to Pyruvate by LDH, and that pyruvate would then go into the mitochondria to fuel aerobic respiration.

So when this page for example, (to quote what I know to be an accurate part of that article), says "lactate produced during exercise can be 'recycled' into glucose and used as fuel by the muscles" It's referring to the cori cycle, since it mentions lactate converting to glucose. Whereas in contrast, that paper, is talking about a process within purely within the muscle. Also the cori cycle is about pyruvate being used for anaerobic metabolism(anaerobic metabolism occurs in the cytoplasm) and the paper mentions about pyruvate being used for aerobic respiration(a reaction in the mitochondria).

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  • $\begingroup$ I think that after Lactate is converted to Pyruvate, then that Pyruvate could be used for either aerobic metabolism or anaerobic m And that similarly, (with the other process, so),when Glucose is converted to Pyruvate, then that Pyruvate could be used to fuel either aerobic m, or anaerobic m. (that is the case though the title of the paper and the concept of the cori cycle don't suggest that, as teh paper is distinguishing itself from the cori cycle by speaking of aerobic, and the cori cycle as a continual cycle is speaking only of anaerobic) I aim to update my answer to make that more clear. $\endgroup$ – barlop Jul 7 '17 at 8:40

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