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Does lactic acid fermentation in humans happen only in the muscle? I have read in this Wikipedia page that human muscle cells sometimes respire anaerobically to produce ATP and lactic acid. Does it happen anywhere else in our body?

My research:
Cells which lack mitochondria or do not have enough supply of oxygen perform lactic acid fermentation for the energy.

Aerobic and anaerobic respiration:
The NADH gets converted to NAD+ during the process of fermentation. Aerobic respiration and anaerobic respiration follow through glycolysis, the Krebs cycle and finally the Electron Transport Chain (ETC). The difference between aerobic and anaerobic respiration is that, in anaerobic respiration another molecule , other than oxygen, is used as the electron acceptor in the ETC.

Fermentation:
But during fermentation, there is no ETC ( or Krebs cycle). Because of the lack of oxygen, the cells performing fermentation have glycolysis followed by some extra reaction ( to get back NAD+) for their energy requirement in the absence of oxygen. During glycolysis NAD+ gets reduced into NADH. Then the NADH oxidises in the ETC to form NAD+. This can again be used in glycolysis. But there is no ETC in fermentation. So, the pyruvate (or a derivative of it) after glycolysis acts as the electron acceptor and oxidises the NADH back to NAD+ in fermentation. Based on the electron acceptor during fermentation, it can be classified as lactic acid fermentation or alcoholic fermentation.

The two main type of cells that perform fermentation are the erythrocytes (RBCs) and SKELETAL muscle cells. As mature RBCs lack mitochondria, which is essential for aerobic respiration, they only performs lactic acid fermentation. Skeletal muscle cells on the other hand perform lactic acid fermentation when the energy requirement is higher than the rate at which the muscles cells can get oxygen. This is usually during strenuous exercises.

I would like to know if any other cell in the human body might be doing this. So the answer might be a cell which lacks mitochondria or that experiences hypoxia and needs energy.

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    $\begingroup$ Welcome to SE Biology. There are two situations in which lactic acid fermentation /anaerobic glycolysis occurs — that in which the tissue has insufficient oxygen, and that in which there are no mitochondria to oxidize NADH. A little reflection might suggest to you an example of a cell in which the latter situation exists. $\endgroup$
    – David
    May 16, 2023 at 22:11
  • $\begingroup$ Thank you for that, I have researched some more and would like to know cells in our body that may not have a mitochondria. $\endgroup$
    – Patrick
    May 17, 2023 at 13:42
  • $\begingroup$ What may be the reason for the negative votes on this question? Was it because of no research? $\endgroup$
    – Patrick
    May 17, 2023 at 17:24
  • $\begingroup$ Hello Patrick, yes that's probably the case. It might also be the use of "fermentation". Whilst perhaps not technically incorrect by some definitions, it isn't the usual usage of the word as it would normally apply to microbial activity, not what happens in (healthy) human cells. $\endgroup$ May 17, 2023 at 17:30
  • $\begingroup$ @JiminyCricket. — No, I put that in because anaerobic respiration is wrong (it covers bacteria that use metals rather than oxygen as an electron acceptor). I don’t like it really either. Perhaps anaerobic glycolysis would be better. $\endgroup$
    – David
    May 17, 2023 at 17:36

2 Answers 2

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Certain human tissues can be considered completely aerobic (e.g. liver) or anaerobic (e.g. erythrocytes) in their energy (ATP) production. However it is wrong to think, as some other recent questions or comments have seemed to imply, that the only other tissue that displays anaerobic metabolism — glycolysis followed by conversion of pyruvate to lactate — is skeletal muscle. Certainly the mitochondrial content and blood supply of white muscle during excercise leads to it being the major producer of lactate, but most tissues also have the capability for anaerobic glycolysis, and there exists a spectrum in the relative contribution of aerobic and anaerobic metabolism to energy production.

The primary literature on this is quite old and tends to be of the observation and measurement variety. I will list some lactate-producing tissues with linked ‘medium old’ references, as modern ones tend to have a narrow focus.

Most well established are:

Somewhat less so, perhaps, are:

In addition, it should be noted that many tissues produce lactate in abnormal medical conditions, reviewed here and, from a more surgical viewpoint, here.

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  • $\begingroup$ This is answered on the basis that no other pathway other than anaerobic glycolysis produces lactic acid right? $\endgroup$
    – Patrick
    May 18, 2023 at 10:26
  • $\begingroup$ The historical papers generally measured the production of lactate by tissues. This was assumed to be from pyruvate in a reaction catalysed by lactate dehydrogenase, and subsequent work confirms LDH as the sole enzyme producing lactate. The origin of the pyruvate may or may not be shown to be glycolysis, depending on the study (there are 60 years' worth of papers for you to follow up). However in many/most experiments glucose is the only source of carbohydrate precursor for pyruvate, so this is quite reasonable. In any case there are not a lot of alternative precursors for pyruvate. $\endgroup$
    – David
    May 18, 2023 at 10:55
  • $\begingroup$ This article tells about lactate being the neuronal energy source. I am posting this to ask why you placed brain on the "somewhat less" category. Thus, it is hypothesized that the astrocytes produce lactate which is then taken up by the adjacent neurons and oxidized for fuel. $\endgroup$
    – Patrick
    May 18, 2023 at 11:31
  • $\begingroup$ @Patrick — Yes it looks pretty solid. The source I quote also talks about the "astrocyte–neuron lactate shuttle". This is not my area (as I always say), I just have a vague memory of things I have encountered and know how to search. I'll change it. The answer would be better with a paragraph after each entry, but there's only so much time one can devote to these things. $\endgroup$
    – David
    May 18, 2023 at 17:28
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Well, first, fermentation and anaerobic respiration are separate things. At the elementary level, fermentation only involves glycolosis whereas anaerobic respiration involves all stages of respiration. Anaerobic respiration, which is what occurs in muscles cells once their store of ATP have dried, is incredibly inefficient, with 2 ATP produced per glucose (with Aerobic respiration producing up to 38), and so one would heavily doubt anaerobic respiration occurs in anywhere but muscle tissue, where it is occasionally necessary.

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  • $\begingroup$ In muscle cells aerobic respiration occurs most of the time. I agree with your difference of fermentation and anaerobic respiration. How would you explain the lactic acid formation using anaerobic respiration. Skeletal muscle cells perform lactic acid fermentation. $\endgroup$
    – Patrick
    May 17, 2023 at 13:45

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