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

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


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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


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:

  • 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 $ce{lactate ightarrow pyruvate}$. 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:

  • Lactic Acid - Wikipedia

  • Lactate Dehydrogenase - Wikipedia

  • Cori's Cycle - Wikipedia


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.

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).


This conversion is necessary when a cell has little to no oxygen because NAD + is necessary to continue making ATP through glycolysis. The enzyme creates lactic acid as an end product, in a fermentation reaction. Lactic acid creates the feeling of your muscles “burning” when you exercise hard because it is building up in the cells. However, the true product of lactate dehydrogenase is more electron carriers, specifically NAD + .

Lactate dehydrogenase is present within all the cells of your body and works to maintain homeostasis in the absence of oxygen. When a person exercises hard, oxygen levels within muscle tissues drop quickly. In order for the muscle cells to keep functioning, they need to continue creating ATP. Oxygen is typically the final electron receptor at the end of the electron transport chain. Without it, the chain is halted along with ATP synthase.

To continue functioning, the muscles must use the ATP created by the process of glycolysis. This process, to continue, needs electron carriers. Lactate dehydrogenase, in forming lactic acid, removes electrons from NADH to complete the process. In doing so, NAD + is created and can then be used in glycolysis to create more ATP. While the process produces far less ATP than the electron transport chain, it allows the cell to continue functioning without ample oxygen.


Step 1 : Uptake and Phosphorylation of Glucose

  • Glucose is phosphorylated to form glucose-6-phosphate.
  • Glucose forms glucose-6-phosphate through phosphorylation using glucokinase (an enzyme in the liver) and hexokinase (non-specific liver enzyme) and extrahepatic tissue as catalysts. Such enzymes break down ATP into ADP and add Pi to the glucose.
  • Hexokinase is a key glycolytic enzyme. Hexokinase catalyses a regulatory step in glycolysis that is irreversible.
  • However, for hexokinase’s actions to takes place, it needs Mg2+.

What is the Cori Cycle? (with pictures)

The Cori cycle describes the linked metabolic pathways by which muscles, even in the absence of oxygen, remain capable of functioning. This occurs as a result of the liver’s ability to convert a muscle’s chemical waste product back into its energy source. The cycle was first mapped in 1929 by married physicians Carl and Gerty Cori, who received the 1946 Nobel Prize in Medicine for their eponymous discovery. It explains how glucose can be consumed by muscles, leaching lactate in the process. The liver then uses this lactate to create glucose, all entirely through enzymatic reactions.

Muscles normally combine glucose with oxygen to generate energy. If oxygen is unavailable, the anaerobic breakdown of glucose is achieved through a fermentation process called glycolysis. One of its by-products is lactate, a soluble milk acid that is excreted back into the bloodstream. Among the many biological functions of the liver is gluconeogenesis, the process by which the body maintains the proper blood sugar level through the synthesis of glucose from non-carbohydrate components. Critical to completing this loop is the catalytic co-enzyme adenosine triphosphate (ATP).

In the normal presence of oxygen, glycolysis in muscle cells produces two units of ATP and two units of pyruvate, a simple acid that has been implicated as the possible precursor to organic life. The two compounds provide the energy that enables a cell to perpetuate respiration through a series of chemical reactions called the Krebs cycle, also called the citric acid or tricarboxylic acid cycle. Oxidation pulls a carbon atom and two hydrogen atoms — water and carbon dioxide — out of the equation. The 1953 Nobel Prize was awarded to the biochemist who mapped and named this cyclic process.

In the absence of oxygen, organic enzymes can break down the glucose carbohydrate by fermentation. Plant cells convert pyruvate into an alcohol a dehydrogenase enzyme in muscle cells converts it into lactate and the amino acid alanine. The liver filters the lactate out of blood to reverse engineer it to pyruvate and then into glucose. Though less efficiently than the Cori cycle, the liver is also capable of recycling the alanine back into glucose, plus the waste compound urea, in a process called the alanine cycle. In either case of gluconeogenesis, the sugar returns through the bloodstream to power the high energy demands of muscle cells.

As with most natural cycles, the Cori cycle is not an entirely closed loop. For example, while two ATP molecules are produced by glycolysis in the muscles, it costs the liver six ATP molecules to feed the cycle by gluconeogenesis. Likewise, the Cori cycle has nowhere to start without the initial insertion of two oxygen molecules. Eventually, muscles, not to mention the rest of the body, need a fresh new supply of both oxygen and glucose.

The physiological demands of vigorous exercise quickly engage the Cori cycle to burn and re-create glucose anaerobically. When the demand for energy exceeds the capacity of the liver to convert lactate to glucose, a condition called lactic acidosis can occur. The excess lactic acid lowers the pH of blood to a tissue damaging level, and symptoms of distress will include deep hyperventilation, vomiting, and abdominal cramping. Lactic acidosis is the underlying cause of rigor mortis. With the body no longer breathing, all its muscles continue consuming glucose through uninterrupted repetition of the Cori cycle.


Energy cost of the glucose-lactate cycle

The Cori cycle results in a net consumption of 4 ATP.
The gluconeogenic leg of the cycle consumes 2 GTP and 4 ATP per molecule of glucose synthesized, that is, 6 ATP.
The ATP-consuming reactions are catalyzed by:

  • pyruvate carboxylase (EC 6.4.1.1): one ATP
  • phosphoenolpyruvate carboxykinase (EC 4.1.1.32): one GTP
  • glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12): one ATP.

Since two molecules of lactate are required for the synthesis of one molecule of glucose, the net cost is 2 x 3 = 6 high energy bonds per molecule of glucose.
Conversely, the glycolytic leg of the cycle produces only 2 ATP per molecule of glucose.
Therefore, more energy is required to produce glucose from lactate than that obtained by anaerobic glycolysis in extrahepatic tissues. This explains why the Cori cycle cannot be sustained indefinitely.

Is the Cori cycle a futile cycle?

The continuous breakdown and resynthesis of glucose, feature of the Cori cycle, might seem like a waste of energy. Indeed, this cycle allows the effective functioning of many extrahepatic cells at the expense of the liver and partly of the renal cortex. Below, two examples.

  • Red blood cells
    These cells, lacking a nucleus, ribosomes, and mitochondria, are smaller than most other cells. Their small size allows them to pass through tiny capillaries. However, the lack of mitochondria makes them completely dependent on anaerobic glycolysis for ATP production. Then, the lactate is partly disposed of by the liver and renal cortex.
  • Skeletal muscle
    Its cells, and particularly fast-twitch fibers contracting under low oxygen conditions, such as during intense exercise, produce much lactate.
    In such conditions, anaerobic glycolysis leads to the production of 2 ATP per molecule of glucose, 3 if the glucose comes from muscle glycogen, therefore, much lower than the 29-30 ATP produced by the complete oxidation of the monosaccharide. However, the rate of ATP production by anaerobic glycolysis is greater than that produced by the complete oxidation of glucose. Therefore, to meet the energy requirements of contracting muscle, anaerobic glycolysis is an effective means of ATP production. But this could lead to an intracellular accumulation of lactate, and a consequent reduction in intracellular pH. Obviously, such accumulation does not occur, due also to the Cori cycle, in which the liver pays the cost of the disposal of a large part of the muscle lactate, thereby allowing the muscle to use ATP for the contraction.
    And the oxygen debt, which always occurs after a strenuous exercise, is largely due to the increased oxygen demand of the hepatocytes, in which the oxidation of fatty acids, their main fuel, provides the ATP required for gluconeogenesis from lactate.
  • During trauma, sepsis, burns, or after major surgery, an intense cell proliferation occurs in the wound, that is a hypoxic tissue, and in bone marrow. This in turn results in greater production of lactate, an increase in the flux through the Cori cycle and an increase in ATP consumption in the liver, which, as previously said, is supported by an increase in fatty acid oxidation. Hence, the nutrition plan provided to these patients must be taken into account this increase in energy consumption.
  • A similar condition seems to occur also in cancer patients with progressive weight loss.
  • The Cori cycle is also important during overnight fasting and starvation.

A Brief Explanation of the Importance of Cori Cycle in Metabolism

The Cori cycle is an important metabolic process that helps our bodies produce the additional amount of energy required by the muscles to perform grueling activity. This BiologyWise post provides a brief explanation about the Cori cycle.

The Cori cycle is an important metabolic process that helps our bodies produce the additional amount of energy required by the muscles to perform grueling activity. This BiologyWise post provides a brief explanation about the Cori cycle.

Did You Know?

The Cori cycle is named after physicians Carl and Gerty Cori (married couple), who first mapped it in 1929.

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To understand how the human body functions, it is essential to analyze the numerous smaller processes that take place within it. These dependent and independent processes work together in tandem, allowing us to live and perform all our daily activities.

The Cori cycle is one such important process that helps the human body produce the energy required by our muscles when performing a strenuous activity. The following is a description of the working and significance of the Cori cycle, starting with a discussion on how the energy required by our muscles is produced.

Energy Production for Muscle Activity

The muscles in our body enable us to perform all our daily activities, including walking, standing, running, lifting weights, etc. They produce an amount of force which is directly proportional to the intensity of the activity that is being performed. For the generation of this force, energy is needed.

For muscular activity, ATP (adenosine triphosphate) is required, which is produced in a process known as glycogenolysis. Glycogenolysis breaks down glycogen, which is stored in the skeletal muscles releasing glucose.

For most of our daily activities, our muscles combine glucose and oxygen aerobically, in a process known as glycolysis, which results in the production of two units of ATP and two units of pyruvate. ATP is directly used for energy generation, and when enough oxygen is available, pyruvate too is further broken down aerobically for generating more energy. Thus, these two metabolic compounds provide energy at the cellular level to the muscles, allowing them to function.

However, when we perform a highly strenuous muscular activity, the amount of oxygen intake becomes disproportional (much less) to the energy requirement of the muscles. In such a scenario, since oxygen is insufficient, glucose is broken down through an anaerobic metabolism process known as fermentation, wherein, the pyruvate is converted to lactate – a soluble milk acid, and then secreted into the bloodstream.

This allows the chemical process responsible for energy generation to continue without the use of oxygen. In this manner, the muscle cells can produce energy anaerobically in this at very high rates, but only for about one to three minutes, after which lactate accumulation in the bloodstream becomes excessive, which leads to fatigue.

What is the Cori Cycle?

If a strenuous activity continues, the body adopts an alternate metabolic route to get rid of the lactate, and keep producing energy anaerobically. This process of energy production is known as the Cori cycle.

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In the Cori cycle, lactate accumulated in the muscle cells is taken up by the liver. The liver performs a chemical process known as gluconeogenesis, to convert lactate back to glucose.

Essentially, gluconeogenesis reverses both the processes of glycolysis and fermentation that the body had performed to produce lactate. This first converts lactate to pyruvate, and then finally into glucose.

This glucose is then introduced into the bloodstream, which carries it to the working muscles, where it is used to feed the additional energy demands of the muscles. The subsequent lactate production by the muscles is again taken up by the liver, and thus the Cori cycle resumes.

In case the muscular activity ceases, the glucose generated in the Cori cycle undergoes glycogenesis to replenish the glycogen stored in the muscles.

Limitations of the Cori Cycle

Using the Cori cycle, the human body is able to convert metabolic by products into a source of energy for the muscles. However, it cannot continue to do so infinitely.

Similar to many other natural cycles, the Cori cycle isn’t a completely closed loop. In the muscles, glycolysis results in the production of two units of ATP. However, the liver uses up six units of ATP to carry out the process of gluconeogenesis. The Cori cycle also requires the initial introduction of oxygen, without which it cannot begin. As such, eventually, the muscles are bound to require a new supply of glucose as well as oxygen.

If a physical activity is too strenuous, the energy requirements of the muscles will exceed the capacity of the Cori cycle to regenerate glucose from lactate. This will result in a condition known as lactic acidosis, which is an accumulation of excess lactic acid in the system. Lactic acidosis brings down the pH level of the blood, which can lead to tissue damage. It also induces symptoms associated with panic, such as hyperventilation, abdominal cramps, vomiting, etc., all of which are the body’s natural defense mechanisms designed to slow down the rigorous activity, and prevent permanent damage from occurring.

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16.1.4. Triose phosphate isomerase Salvages a Three-Carbon Fragment

Glyceraldehyde 3-phosphate is on the direct pathway of glycolysis, whereas dihydroxyacetone phosphate is not. Unless a means exists to convert dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, a three-carbon fragment useful for generating ATP will be lost. These compounds are isomers that can be readily interconverted: dihydroxyacetone phosphate is a ketose, whereas glyceraldehyde 3-phosphate is an aldose. The isomerization of these three-carbon phosphorylated sugars is catalyzed by triose phosphate isomerase (TIM Figure 16.5). This reaction is rapid and reversible. At equilibrium, 96% of the triose phosphate is dihydroxyacetone phosphate. However, the reaction proceeds readily from dihydroxyacetone phosphate to glyceraldehyde 3-phosphate because the subsequent reactions of glycolysis remove this product.

Figure 16.5

Structure of Triose Phosphate Isomerase. This enzyme consists of a central core of eight parallel β strands (orange) surrounded by eight α helices (blue). This structural motif, called an αβ barrel, is also found in the (more. )

Much is known about the catalytic mechanism of triose phosphate isomerase. TIM catalyzes the transfer of a hydrogen atom from carbon 1 to carbon 2 in converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, an intramolecular oxidation-reduction. This isomerization of a ketose into an aldose proceeds through an enediol intermediate (Figure 16.6).

Figure 16.6

Catalytic Mechanism of Triose Phosphate Isomerase. Glutamate 165 transfers a proton between carbons with the assistance of histidine 95, which shuttles between the neutral and relatively rare negatively charged form. The latter is stabilized by interactions (more. )

X-ray crystallographic and other studies showed that glutamate 165 (see Figure 16.5) plays the role of a general acid-base catalyst. However, this carboxylate group by itself is not basic enough to pull a proton away from a carbon atom adjacent to a carbonyl group. Histidine 95 assists catalysis by donating a proton to stabilize the negative charge that develops on the C-2 carbonyl group.

Two features of this enzyme are noteworthy. First, TIM displays great catalytic prowess. It accelerates isomerization by a factor of 10 10 compared with the rate obtained with a simple base catalyst such as acetate ion. Indeed, the kcat/KM ratio for isomerization of glyceraldehyde 3-phosphate is 2 × 10 8 M -1 s -1 , which is close to the diffusion-controlled limit. In other words, the rate-limiting step in catalysis is the diffusion-controlled encounter of substrate and enzyme. TIM is an example of a kinetically perfect enzyme (Section 8.2.5). Second, TIM suppresses an undesired side reaction, the decomposition of the enediol intermediate into methyl glyoxal and inorganic phosphate.

In solution, this physiologically useless reaction is 100 times as fast as isomerization. Hence, TIM must prevent the enediol from leaving the enzyme. This labile intermediate is trapped in the active site by the movement of a loop of 10 residues (see Figure 16.5). This loop serves as a lid on the active site, shutting it when the enediol is present and reopening it when isomerization is completed. We see here a striking example not only of catalytic perfection, but also of the acceleration of a desirable reaction so that it takes place much faster than an undesirable alternative reaction. Thus, two molecules of glyceraldehyde 3-phosphate are formed from one molecule of fructose 1,6-bisphosphate by the sequential action of aldolase and triose phosphate isomerase. The economy of metabolism is evident in this reaction sequence. The isomerase funnels dihydroxyacetone phosphate into the main glycolytic pathway𠅊 separate set of reactions is not needed.


2. Glycolysis

Glycolysis is the predominant energy system used for all-out exercise lasting from 30 seconds to about 2 minutes and is the second-fastest way to resynthesize ATP. During glycolysis, carbohydrate—in the form of either blood glucose (sugar) or muscle glycogen (the stored form of glucose)—is broken down through a series of chemical reactions to form pyruvate (glycogen is first broken down into glucose through a process called glycogenolysis).

For every molecule of glucose broken down to pyruvate through glycolysis, two molecules of usable ATP are produced (Brooks et al. 2000). Thus, very little energy is produced through this pathway, but the trade-off is that you get the energy quickly. Once pyruvate is formed, it has two fates: conversion to lactate or conversion to a metabolic intermediary molecule called acetyl coenzyme A (acetyl-CoA), which enters the mitochondria for oxidation and the production of more ATP (Robergs & Roberts 1997). Conversion to lactate occurs when the demand for oxygen is greater than the supply (i.e., during anaerobic exercise). Conversely, when there is enough oxygen available to meet the muscles’ needs (i.e., during aerobic exercise), pyruvate (via acetyl-CoA) enters the mitochondria and goes through aerobic metabolism.

When oxygen is not supplied fast enough to meet the muscles’ needs (anaerobic glycolysis), there is an increase in hydrogen ions (which causes the muscle pH to decrease a condition called acidosis) and other metabolites (ADP, Pi and potassium ions). Acidosis and the accumulation of these other metabolites cause a number of problems inside the muscles, including inhibition of specific enzymes involved in metabolism and muscle contraction, inhibition of the release of calcium (the trigger for muscle contraction) from its storage site in muscles, and interference with the muscles’ electrical charges (Enoka & Stuart 1992 Glaister 2005 McLester 1997). As a result of these changes, muscles lose their ability to contract effectively, and muscle force production and exercise intensity ultimately decrease.


Contents

Swedish chemist Carl Wilhelm Scheele was the first person to isolate lactic acid in 1780 from sour milk. [16] The name reflects the lact- combining form derived from the Latin word lac, which means milk. In 1808, Jöns Jacob Berzelius discovered that lactic acid (actually L -lactate) also is produced in muscles during exertion. [17] Its structure was established by Johannes Wislicenus in 1873.

In 1856, the role of Lactobacillus in the synthesis of lactic acid was discovered by Louis Pasteur. This pathway was used commercially by the German pharmacy Boehringer Ingelheim in 1895.

In 2006, global production of lactic acid reached 275,000 tonnes with an average annual growth of 10%. [18]

Lactic acid is produced industrially by bacterial fermentation of carbohydrates, or by chemical synthesis from acetaldehyde. [19] In 2009, lactic acid was produced predominantly (70–90%) [20] by fermentation. Production of racemic lactic acid consisting of a 1:1 mixture of D and L stereoisomers, or of mixtures with up to 99.9% L -lactic acid, is possible by microbial fermentation. Industrial scale production of D -lactic acid by fermentation is possible, but much more challenging.

Fermentative production Edit

As a starting material for industrial production of lactic acid, almost any carbohydrate source containing C5 and C6 sugars can be used. Pure sucrose, glucose from starch, raw sugar, and beet juice are frequently used. [21] Lactic acid producing bacteria can be divided in two classes: homofermentative bacteria like Lactobacillus casei and Lactococcus lactis, producing two moles of lactate from one mole of glucose, and heterofermentative species producing one mole of lactate from one mole of glucose as well as carbon dioxide and acetic acid/ethanol. [22]

Chemical production Edit

Racemic lactic acid is synthesized industrially by reacting acetaldehyde with hydrogen cyanide and hydrolysing the resultant lactonitrile. When hydrolysis is performed by hydrochloric acid, ammonium chloride forms as a by-product the Japanese company Musashino is one of the last big manufacturers of lactic acid by this route. [23] Synthesis of both racemic and enantiopure lactic acids is also possible from other starting materials (vinyl acetate, glycerol, etc.) by application of catalytic procedures. [24]

Molecular biology Edit

Exercise and lactate Edit

During power exercises such as sprinting, when the rate of demand for energy is high, glucose is broken down and oxidized to pyruvate, and lactate is then produced from the pyruvate faster than the body can process it, causing lactate concentrations to rise. The production of lactate is beneficial for NAD + regeneration (pyruvate is reduced to lactate while NADH is oxidized to NAD + ), which is used up in oxidation of glyceraldehyde 3-phosphate during production of pyruvate from glucose, and this ensures that energy production is maintained and exercise can continue. During intense exercise, the respiratory chain cannot keep up with the amount of hydrogen ions that join to form NADH, and cannot regenerate NAD + quickly enough.

The resulting lactate can be used in two ways:

    back to pyruvate by well-oxygenated muscle cells, heart cells, and brain cells
    • Pyruvate is then directly used to fuel the Krebs cycle
    • If blood glucose concentrations are high, the glucose can be used to build up the liver's glycogen stores.

    However, lactate is continually formed even at rest and during moderate exercise. Some causes of this are metabolism in red blood cells that lack mitochondria, and limitations resulting from the enzyme activity that occurs in muscle fibers having high glycolytic capacity. [25]

    In 2004, Robergs et al. maintained that lactic acidosis during exercise is a "construct" or myth, pointing out that part of the H + comes from ATP hydrolysis (ATP 4− + H2O → ADP 3− + HPO 2−
    4 + H + ), and that reducing pyruvate to lactate (pyruvate − + NADH + H + → lactate − + NAD + ) actually consumes H + . [26] Lindinger et al. [27] countered that they had ignored the causative factors of the increase in [H + ]. After all, the production of lactate − from a neutral molecule must increase [H + ] to maintain electroneutrality. The point of Robergs's paper, however, was that lactate − is produced from pyruvate − , which has the same charge. It is pyruvate − production from neutral glucose that generates H + :

    C6H12O6 + 2 NAD + + 2 ADP 3− + 2 HPO 2−
    4
    2 CH
    3 COCO −
    2 + 2 H + + 2 NADH + 2 ATP 4− + 2 H2O
    Subsequent lactate − production absorbs these protons:
    2 CH
    3 COCO −
    2 + 2 H + + 2 NADH
    2 CH
    3 CH(OH)CO −
    2 + 2 NAD +
    Overall:
    C6H12O6 + 2 NAD + + 2 ADP 3− + 2 HPO 2−
    4
    2 CH
    3 COCO −
    2 + 2 H + + 2 NADH + 2 ATP 4− + 2 H2O
    2 CH
    3 CH(OH)CO −
    2 + 2 NAD + + 2 ATP 4− + 2 H2O

    Although the reaction glucose → 2 lactate − + 2 H + releases two H + when viewed on its own, the H + are absorbed in the production of ATP. On the other hand, the absorbed acidity is released during subsequent hydrolysis of ATP: ATP 4− + H2O → ADP 3− + HPO 2−
    4 + H + . So once the use of ATP is included, the overall reaction is

    The generation of CO2 during respiration also causes an increase in [H + ].

    Neural tissue energy source Edit

    Although glucose is usually assumed to be the main energy source for living tissues, there are a few reports that indicate that it is lactate, and not glucose, that is preferentially metabolized by neurons in the brain of several mammalian species (the notable ones being mice, rats, and humans). [28] [29] [ non-primary source needed ] According to the lactate-shuttle hypothesis, glial cells are responsible for transforming glucose into lactate, and for providing lactate to the neurons. [30] [31] Because of this local metabolic activity of glial cells, the extracellular fluid immediately surrounding neurons strongly differs in composition from the blood or cerebrospinal fluid, being much richer with lactate, as was found in microdialysis studies. [28]

    Brain development metabolism Edit

    Some evidence suggests that lactate is important at early stages of development for brain metabolism in prenatal and early postnatal subjects, with lactate at these stages having higher concentrations in body liquids, and being utilized by the brain preferentially over glucose. [28] It was also hypothesized that lactate may exert a strong action over GABAergic networks in the developing brain, making them more inhibitory than it was previously assumed, [32] acting either through better support of metabolites, [28] or alterations in base intracellular pH levels, [33] [34] or both. [35]

    Studies of brain slices of mice show that β-hydroxybutyrate, lactate, and pyruvate act as oxidative energy substrates, causing an increase in the NAD(P)H oxidation phase, that glucose was insufficient as an energy carrier during intense synaptic activity and, finally, that lactate can be an efficient energy substrate capable of sustaining and enhancing brain aerobic energy metabolism in vitro. [36] The study "provides novel data on biphasic NAD(P)H fluorescence transients, an important physiological response to neural activation that has been reproduced in many studies and that is believed to originate predominately from activity-induced concentration changes to the cellular NADH pools." [37]

    Lactate can also serve as an important source of energy for other organs, including the heart and liver. During physical activity, up to 60% of the heart muscle's energy turnover rate derives from lactate oxidation. [16]

    Blood tests for lactate are performed to determine the status of the acid base homeostasis in the body. Blood sampling for this purpose is often arterial (even if it is more difficult than venipuncture), because lactate levels differ substantially between arterial and venous, and the arterial level is more representative for this purpose.

    Reference ranges
    Lower limit Upper limit Unit
    Venous 4.5 [38] 19.8 [38] mg/dL
    0.5 [39] 2.2 [39] mmol/L
    Arterial 4.5 [38] 14.4 [38] mg/dL
    0.5 [39] 1.6 [39] mmol/L

    During childbirth, lactate levels in the fetus can be quantified by fetal scalp blood testing.

    Two molecules of lactic acid can be dehydrated to the lactone lactide. In the presence of catalysts lactide polymerize to either atactic or syndiotactic polylactide (PLA), which are biodegradable polyesters. PLA is an example of a plastic that is not derived from petrochemicals.

    Lactic acid is also employed in pharmaceutical technology to produce water-soluble lactates from otherwise-insoluble active ingredients. It finds further use in topical preparations and cosmetics to adjust acidity and for its disinfectant and keratolytic properties.

    Lactic acid is found primarily in sour milk products, such as kumis, laban, yogurt, kefir, and some cottage cheeses. The casein in fermented milk is coagulated (curdled) by lactic acid. Lactic acid is also responsible for the sour flavor of sourdough bread.

    In lists of nutritional information lactic acid might be included under the term "carbohydrate" (or "carbohydrate by difference") because this often includes everything other than water, protein, fat, ash, and ethanol. [40] If this is the case then the calculated food energy may use the standard 4 kilocalories (17 kJ) per gram that is often used for all carbohydrates. But in some cases lactic acid is ignored in the calculation. [41] The energy density of lactic acid is 362 kilocalories (1,510 kJ) per 100 g. [42]

    Some beers (sour beer) purposely contain lactic acid, one such type being Belgian lambics. Most commonly, this is produced naturally by various strains of bacteria. These bacteria ferment sugars into acids, unlike the yeast that ferment sugar into ethanol. After cooling the wort, yeast and bacteria are allowed to “fall” into the open fermenters. Brewers of more common beer styles would ensure that no such bacteria are allowed to enter the fermenter. Other sour styles of beer include Berliner weisse, Flanders red and American wild ale. [43] [44]

    In winemaking, a bacterial process, natural or controlled, is often used to convert the naturally present malic acid to lactic acid, to reduce the sharpness and for other flavor-related reasons. This malolactic fermentation is undertaken by lactic acid bacteria.

    While not normally found in significant quantities in fruit, lactic acid is the primary organic acid in akebia fruit, making up 2.12% of the juice. [45]

    As a food additive it is approved for use in the EU, [46] USA [47] and Australia and New Zealand [48] it is listed by its INS number 270 or as E number E270. Lactic acid is used as a food preservative, curing agent, and flavoring agent. [49] It is an ingredient in processed foods and is used as a decontaminant during meat processing. [50] Lactic acid is produced commercially by fermentation of carbohydrates such as glucose, sucrose, or lactose, or by chemical synthesis. [49] Carbohydrate sources include corn, beets, and cane sugar. [51]

    Lactic acid has historically been used to assist with the erasure of inks from official papers to be modified during forgery. [52]

    Lactic acid is used in some liquid cleaners as a descaling agent for removing hard water deposits such as calcium carbonate, forming the lactate, Calcium lactate. Owing to its high acidity, such deposits are eliminated very quickly, especially where boiling water is used, as in kettles. It also is gaining popularity in antibacterial dish detergents and hand soaps replacing Triclosan.


    Why Does Lactic Acid Build Up in Muscles? And Why Does It Cause Soreness?

    As our bodies perform strenuous exercise, we begin to breathe faster as we attempt to shuttle more oxygen to our working muscles. The body prefers to generate most of its energy using aerobic methods, meaning with oxygen. Some circumstances, however&mdashsuch as evading the historical saber tooth tiger or lifting heavy weights&mdashrequire energy production faster than our bodies can adequately deliver oxygen. In those cases, the working muscles generate energy anaerobically. This energy comes from glucose through a process called glycolysis, in which glucose is broken down or metabolized into a substance called pyruvate through a series of steps. When the body has plenty of oxygen, pyruvate is shuttled to an aerobic pathway to be further broken down for more energy. But when oxygen is limited, the body temporarily converts pyruvate into a substance called lactate, which allows glucose breakdown&mdashand thus energy production&mdashto continue. The working muscle cells can continue this type of anaerobic energy production at high rates for one to three minutes, during which time lactate can accumulate to high levels.

    A side effect of high lactate levels is an increase in the acidity of the muscle cells, along with disruptions of other metabolites. The same metabolic pathways that permit the breakdown of glucose to energy perform poorly in this acidic environment. On the surface, it seems counterproductive that a working muscle would produce something that would slow its capacity for more work. In reality, this is a natural defense mechanism for the body it prevents permanent damage during extreme exertion by slowing the key systems needed to maintain muscle contraction. Once the body slows down, oxygen becomes available and lactate reverts back to pyruvate, allowing continued aerobic metabolism and energy for the body&rsquos recovery from the strenuous event.

    Contrary to popular opinion, lactate or, as it is often called, lactic acid buildup is not responsible for the muscle soreness felt in the days following strenuous exercise. Rather, the production of lactate and other metabolites during extreme exertion results in the burning sensation often felt in active muscles, though which exact metabolites are involved remains unclear. This often painful sensation also gets us to stop overworking the body, thus forcing a recovery period in which the body clears the lactate and other metabolites.

    Researchers who have examined lactate levels right after exercise found little correlation with the level of muscle soreness felt a few days later. This delayed-onset muscle soreness, or DOMS as it is called by exercise physiologists, is characterized by sometimes severe muscle tenderness as well as loss of strength and range of motion, usually reaching a peak 24 to 72 hours after the extreme exercise event.

    Though the precise cause of DOMS is still unknown, most research points to actual muscle cell damage and an elevated release of various metabolites into the tissue surrounding the muscle cells. These responses to extreme exercise result in an inflammatory-repair response, leading to swelling and soreness that peaks a day or two after the event and resolves a few days later, depending on the severity of the damage. In fact, the type of muscle contraction appears to be a key factor in the development of DOMS. When a muscle lengthens against a load&mdashimagine your flexed arms attempting to catch a thousand pound weight&mdashthe muscle contraction is said to be eccentric. In other words, the muscle is actively contracting, attempting to shorten its length, but it is failing. These eccentric contractions have been shown to result in more muscle cell damage than is seen with typical concentric contractions, in which a muscle successfully shortens during contraction against a load. Thus, exercises that involve many eccentric contractions, such as downhill running, will result in the most severe DOMS, even without any noticeable burning sensations in the muscles during the event.

    Given that delayed-onset muscle soreness in response to extreme exercise is so common, exercise physiologists are actively researching the potential role for anti-inflammatory drugs and other supplements in the prevention and treatment of such muscle soreness, but no conclusive recommendations are currently available. Although anti-inflammatory drugs do appear to reduce the muscle soreness&mdasha good thing&mdashthey may slow the ability of the muscle to repair the damage, which may have negative consequences for muscle function in the weeks following the strenuous event.



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