PYRUVATE: PROPERTIES, SYNTHESIS, BIOLOGICAL ROLE, APPLICATIONS - CHEMISTRY - 2025

The pyruvate or pyruvic acid is the simplest ketoacid. It has a three-carbon molecule with a carboxyl group adjacent to a ketone carbon. This compound is the end product of glycolysis and constitutes a crossroads for the development of numerous metabolic processes.

Glycolysis is a metabolic pathway that breaks down glucose. It consists of ten steps in which one molecule of glucose is transformed into two molecules of pyruvate, with the net generation of two molecules of ATP.

Skeleton of the pyruvic acid molecule. Source: Lukáš Mižoch

In the first five steps of glycolysis there is an consumption of two ATP molecules for the production of phosphate sugars: glucose-6-phosphate and fructose-1,6-bisphosphate. In the last five reactions of glycolysis, energy and four ATP molecules are generated.

Pyruvic acid is produced from phosphoenolpyruvic acid or phosphoenolpyruvate, in a reaction catalyzed by the enzyme pyruvate kinase; an enzyme that requires Mg ²⁺ and K ⁺. During the reaction, the production of an ATP molecule occurs.

The pyruvic acid produced can be used in different biochemical events; depending on whether the glycolysis has been performed under aerobic conditions, or under anaerobic conditions.

Under aerobic conditions, pyruvic acid is transformed into acetylCoA, and this is incorporated into the Krebs cycle or the tricarboxylic acids. Glucose ends up transforming during the electronic transport chain, a process that occurs after glycolysis, into carbon dioxide and water.

Under anaerobic conditions, pyruvic acid is transformed into lactate by the action of the enzyme lactic dehydrogenase. This occurs in higher organisms, including mammals and bacteria in milk.

However, yeasts ferment pyruvic acid into acetaldehyde by the action of the enzyme pyruvate decarboxylase. The acetaldehyde is subsequently transformed into ethanol.

Properties

Molecular formula

C ₃ H ₄ O ₃

Chemical names

-Pyruvic acid, -Pyroacemic acid and

-2-oxopropionic (IUPAC name).

Molar mass

88.062 g / mol.

Physical description

Colorless liquid, which can also be yellowish or amber in color.

Odor

Pungent odor similar to acetic acid.

Boiling point

54 ° C.

Melting point

13.8 ° C.

Density

1.272 g / cm ³ at 20 ° C.

Water solubility

10 ⁶ mg / L at 20 ° C; or what is the same, generates a solution with a molar concentration of 11.36 M.

Vapor pressure

129 mmHg.

Octanol / water partition coefficient

Log P = -0.5

Acidity

pKa = 2.45 at 25 ºC

Refractive index

η20D = 1.428

Storage temperature

2 - 8 ºC

pH

1.2 at a concentration of 90 g / L of water at 20 ºC.

Stability

Stable, but combustible. Incompatible with strong oxidizing agents and strong bases. It polymerizes and decomposes during storage if the container does not protect it from air and light.

Flavor threshold

5 ppm.

Synthesis

It is prepared by heating tartaric acid with molten potassium bisulfate (KHSO ₄), at a temperature of 210 ° C - 220 ° C. The reaction product is purified by fractional distillation under reduced pressure.

Thiamine auxotrophic yeasts are capable of synthesizing pyruvic acid when grown in glycerol and propionic acid. Pyruvic acid has a 71% yield from glycerol.

Pyruvic acid is also produced by the oxidation of propylene glycol with an oxidant such as potassium permanganate.

Biological role

Destinations

Pyruvic acid is not an essential nutrient, since it is produced in all living organisms; for example, a red apple contains 450 mg of this compound, which constitutes a crossroads for the development of various metabolic processes.

When it is formed during glycolysis, it can have several destinations: to become acetylCoA to be used in the Krebs cycle; transform into lactic acid; or in amino acids.

In addition, pyruvic acid can be incorporated, without the need to convert to acetylCoA, into the Krebs cycle through an anaplerotic route.

Conversion to acetylCoA

In the conversion of pyruvic acid to acetylCoA a decarboxylation of pyruvic acid occurs, and the remaining acetyl group combines with coenzymeA to form acetylCoA. It is a complex process catalyzed by the enzyme pyruvate dehydrogenase.

This enzyme forms a complex with two other enzymes to catalyze the synthesis of acetylCoA: dihydrolipoamide transacetylase and dihydrolipoamide dehydrogenase. In addition, five coenzymes participate in the synthesis: thiamine pyrophosphate, lipoic acid, FADH ₂, NADH and CoA.

In cases of vitamin B ₁ (thiamine) deficiency, pyruvic acid accumulates in nerve structures. In addition to the acetylCoA originating from pyruvic acid, the one from the metabolism of amino acids and from the β-oxidation of fatty acids is used in the Krebs cycle.

The two-carbon acetyl CoA combines with the four-carbon oxaloacetate to form the six-carbon citrate. This event is followed by a sequence of reactions, which together are called the Krebs cycle or the tricarboxylic acid cycle.

Krebs cycle

In the Krebs cycle, the coenzymes NADH and FADH _{2 are produced}, which are used in a sequence of reactions in which proteins called cytochromes are involved. This set of reactions is called the electronic transport chain.

The electron transport chain is coupled to oxidative phosphorylation, a metabolic activity in which ATP is produced. For every glucose molecule metabolized through glycolysis, electron transport chain, and oxidative phosphorylation, a total of 36 ATP molecules are produced.

Conversion to oxaloacetate

Pyruvic acid, in an anaplerotic reaction, is carboxylated to oxaloacetate, joining the Krebs cycle. Anaplerotic reactions supply the components of metabolic cycles, preventing their exhaustion. The conversion of pyruvic acid to oxaloacetate is dependent on ATP.

This anaplerotic reaction takes place mainly in the liver of animals. Pyruvic acid is also incorporated into the Krebs cycle transforming into malate, in an anaplerotic reaction catalyzed by the malic enzyme using NADPH as a coenzyme.

Conversion to alanine

Pyruvic acid under starvation conditions undergoes the incorporation of an amino group from glutamic acid in the muscles, thus transforming into the amino acid alanine. This reaction is catalyzed by the enzyme alanine aminotransferase.

Alanine passes into the blood and the reverse process occurs in the liver, transforming alanine into pyruvic acid, and this in turn produces glucose. This sequence of events is called the Cahill Cycle.

Conversion to lactate

In aerobic cells with a high rate of glycolysis, the synthesized NADH molecules are not adequately converted to NAD molecules in mitochondrial oxidation. Therefore, in this case, as in anaerobic cells, the reduction of pyruvic acid to lactate occurs.

This explains what happens during intense exercise, during which glycolysis and the production of NADH are activated, where this NADH is used in the reduction of pyruvic acid into lactic acid. This leads to a build-up of lactic acid in the muscle and therefore pain.

This also occurs in eukaryotic cells, such as lactic acid bacteria; such is the case of lactobacillus. The conversion of pyruvic acid to lactic acid is catalyzed by the lactic dehydrogenase enzyme that uses NADH as a coenzyme.

Alcoholic fermentation

Pyruvic acid, among other destinations, undergoes alcoholic fermentation. In a first step, the pyruvic acid undergoes decarboxylation, giving rise to the acetaldehyde compound. This reaction is catalyzed by the enzyme pyruvate decarboxylase.

Subsequently, acetaldehyde is transformed into ethanol, in a reaction catalyzed by the alcoholic dehydrogenase enzyme that uses NADH as a coenzyme.

Antioxidant function

Pyruvic acid has an antioxidant function, thus eliminating reactive oxygen species such as hydrogen peroxide and lipid peroxides. Supraphysiological levels of pyruvic acid can increase the concentration of cellular reduced glutathione.

Applications

Medical uses

Pyruvic acid has an inotropic effect on the heart muscle, so its injection or infusion via the intracoronary route increases the contractility or strength of muscle contraction.

However, some toxic effects of this procedure must be considered, since a child who received pyruvate intravenously for the treatment of restrictive cardiomyopathy resulted in the death.

Among the possible mechanisms to explain the inotropic effect of pyruvic acid, is an increase in the generation of ATP and an increase in the phosphorylation potential of ATP. Another explanation is the activation of pyruvate dehydrogenase.

Pyruvic acid has long been sold as a usable compound for weight loss. But, in several studies it has been shown that although it has an effect on weight reduction, it is small and its use for this purpose is not recommended.

In addition, there is evidence that the intake of five grams of pyruvic acid / day has a harmful effect on the digestive system, evidenced by abdominal discomfort and abdominal distortion, gas and diarrhea.

An increase in low-density lipoprotein (LDL) cholesterol, considered “the bad cholesterol”, was also observed.

Other uses

Pyruvic acid is used as a food flavoring agent. It also serves as a raw material for the synthesis of L-tryptophan, L-tyrosine and 3,4-dihydrophenylalanine in various industries.

References

1. Mathews, CK, Van Holde, KE and Ahern, KG (2004). Biochemistry. 3rd Edition. Editorial Pearson Educación, SA
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3. Chemical Book. (2017). Pyruvic acid. Recovered from: chemicalbook.com
4. The Editors of Encyclopaedia Britannica. (August 16, 2018). Pyruvic acid. Encyclopædia Britannica. Recovered from: britannica.com
5. Drugbank. (2019). Pyruvic acid. Recovered from: drugbank.ca
6. Wikipedia. (2019). Pyruvic acid. Recovered from: en.wikipedia.org