Hippuric acid structure, properties, biosynthesis, uses

The hippuric acid is an organic compound of chemical formula C₆H₅CONHCH_twoCOOH. It is formed by the conjugation between benzoic acid C₆H₅COOH and glycine NH_twoCH_twoCOOH. 

Hippuric Acid is a colorless crystalline solid. It comes from the metabolism of aromatic organic compounds in the body of mammals, such as humans, horses, cattle and rodents, among others..

Its biosynthesis occurs in the mitochondria of liver cells or kidney cells, starting from benzoic acid. Once produced, hippuric acid is excreted in the urine. In fact, the name "Hippuric" comes from hippos, Greek word for horse, as it was isolated for the first time from horse urine.

The presence of certain beneficial microorganisms in the human intestine causes certain organic compounds to be absorbed or not and it depends on whether more or less hippuric acid is produced later..

It has been used to determine the degree of exposure to toluene for people who work with solvents. It can be used as an indicator of heart damage in chronic kidney patients. It also has potential use in specialized optical devices.

Article index

• 1 Structure
• 2 Nomenclature
• 3 Properties
  • 3.1 Physical state
  • 3.2 Molecular weight
  • 3.3 Melting point
  • 3.4 Boiling point
  • 3.5 Density
  • 3.6 Solubility
• 4 Location in nature
• 5 Biosynthesis
  • 5.1 Importance of the intestinal microbiota
• 6 Uses
  • 6.1 In occupational medicine
  • 6.2 Antibacterial effect
• 7 Potential uses
  • 7.1 As a biomarker in chronic kidney disease
  • 7.2 As a non-linear optical material
  • 7.3 To reduce the greenhouse effect
• 8 References

Structure

The hippuric acid molecule is made up of a benzoyl C group₆H₅-C = O and a -CH group_two-COOH both attached to an amino group -NH-.

Nomenclature

- Hippuric acid

- N-Benzoyl-glycine

- 2-benzoamidoacetic acid

- Benzoyl-amino-acetic acid

- 2-phenylformamido-acetic acid

- Phenyl-carbonyl-aminoacetic acid

- N- (phenylcarbonyl) glycine

- Hippurate (when in salt form, such as sodium or potassium hippurate)

Properties

Physical state

Colorless crystalline solid with orthorhombic structure.

Molecular weight

179.17 g / mol

Melting point

187-191 ºC

Boiling point

210 ºC (begins to decompose)

Density

1.38 g / cm³

Solubility

Slightly soluble in water: 3.75 g / L

Location in nature

It is a normal component in human urine because it comes from metabolizing aromatic organic compounds that are ingested with food.

Some of these compounds are polyphenols, present in beverages such as tea, coffee, wine and fruit juices..

Polyphenols such as chlorogenic acid, cinnamic acid, quinic acid and (+) - catechin are converted to benzoic acid which is transformed into hippuric acid and excreted in the urine..

Other compounds that also give rise to benzoic acid and therefore hippuric acid are phenylalanine and shikimic or psychic acid..

Benzoic acid is also used as a food preservative, so hippuric acid is also derived from these foods.

There are certain beverages whose ingestion increases the excretion of hippuric acid, for example, apple cider, Gingko biloba, chamomile infusion, or fruits such as blueberries, peaches and plums, among others..

It has also been found in the urine of herbivorous mammals such as cattle and horses, rodents, rats, rabbits, and also cats and some types of monkeys..

Because it was isolated for the first time from the urine of horses, it was assigned the name hippuric from the Greek word hippos what does horse mean.

Biosynthesis

Its biological synthesis occurs within the mitochondria of liver or kidney cells and comes basically from benzoic acid. Requires two steps.

The first step is the conversion of benzoic acid to benzoyladenylate. This step is catalyzed by the enzyme benzoyl-CoA synthetase..

In the second step, glycine crosses the mitochondrial membrane and reacts with benzoyladenylate, generating hippurate. This is catalyzed by the enzyme benzoylCoA-glycine N-acyltransferase..

Importance of the gut microbiota

There is evidence that high molecular weight polyphenolic compounds are not well absorbed in the human intestine. The metabolization of polyphenols in the human intestine is carried out by naturally colonizing microbes known as the microbiota..

The microbiota acts through various types of reactions such as dehydroxylation, reduction, hydrolysis, decarboxylation and demethylation.

For example, microorganisms break the catechin ring to valerolactone, which is then transformed to phenylpropionic acid. This is absorbed by the intestine and metabolized in the liver, generating benzoic acid..

Other studies indicate that the hydrolysis of chlorogenic acid by the gut microbiota produces caffeic acid and quinic acid. Caffeic acid is reduced to 3,4-dihydroxy-phenyl-propionic acid and then dehydroxylated to 3-hydroxy-phenyl-propionic acid..

Then the latter and quinic acid are converted to benzoic acid and this to hippuric acid..

Certain studies indicate that the presence of a certain type of intestinal microbiota is essential for the metabolism of phenolic components of food and consequently for the production of hippurate.

And it has been found that by changing the type of diet the intestinal microbiota can change, which can stimulate a greater or lesser production of hippuric acid..

Applications

In occupational medicine

Hippuric acid is used as a biomarker in the biological monitoring of occupational exposure to high concentrations of toluene in air..

After its absorption by inhalation, toluene in the human body is metabolized to hippuric acid via benzoic acid..

Despite its lack of specificity towards toluene, a good correlation has been found between the concentration of toluene in the air of the work environment and the levels of hippuric acid in the urine..

It is the most used indicator in the monitoring of toluene in exposed workers.

The most important sources of hippuric acid generation by exposed workers are environmental contamination with toluene and food..

Workers in the shoe industry are exposed to organic solvents, especially toluene. People who work with oily paints are also exposed to toluene from solvents.

Acute and chronic exposure to toluene causes multiple effects in the human body, as it affects the nervous, gastrointestinal, renal and cardiovascular systems.

It is for these reasons that monitoring for hippuric acid in the urine of these toluene-exposed workers is so important..

Antibacterial effect

Certain sources of information report that an increase in the concentration of hippuric acid in the urine may have an antibacterial effect..

Potential uses

As a biomarker in chronic kidney disease

Some researchers have found that the main route of elimination of hippuric acid is tubular renal secretion and that disruption of this mechanism leads to its accumulation in the blood.

The concentration of hippuric acid in the serum of chronic kidney patients undergoing hemodialysis for many years has been correlated with hypertrophy of the left ventricle of the heart in such patients..

For this reason, it has been proposed as a biomarker or way to determine the overload of the left ventricle of the heart, which is associated with an increased risk of death in patients in the final stage of chronic kidney disease..

As a non-linear optical material

Hippuric acid has been studied as a non-linear optical material.

Non-linear optical materials are useful in the fields of telecommunications, optical computing, and optical data storage..

The optical properties of crystals of hippuric acid doped with sodium chloride NaCl and potassium chloride KCl have been studied. This means that hippuric acid has crystallized with very small amounts of these salts in its crystalline structure..

Doping salts have been observed to improve second harmonic generation efficiency, an important property for non-linear optical materials. They also increase the thermal stability and microhardness of hippuric acid crystals..

Furthermore, studies in the UV-Visible region confirm that doped crystals can be very useful in optical windows at wavelengths between 300 and 1200 nm..

All these advantages confirm that hippuric acid doped with NaCl and KCl can be used in the manufacture of non-linear optical devices..

To reduce the greenhouse effect

Some researchers have shown that the increase of hippuric acid by up to 12.6% in the urine of bovines can reduce the emission of N gas by 65%._twoOr into the atmosphere from the grazing ground.

The n_twoOr is it a greenhouse gas with a potential hazard greater than that of CO_two.

One of the most important sources of N_twoOr all over the world it is the urine deposited by ruminant animals, as it comes from the transformation of urea, a nitrogen compound present in urine..

The diet of ruminant animals has a strong influence on the hippuric acid content of their urine..

Therefore, modifying the diet of grazing animals towards obtaining a higher content of hippuric acid in their urine can help mitigate the greenhouse effect..

References

1. Lees, H.J. et al. (2013). Hippurate: The Natural History of a Mammalian-Microbial Cometabolite. Journal of Proteome Research, January 23, 2013. Recovered from pubs.acs.org.
2. Yu, T.-H. et al. (2018) Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients. Clinica Chimica Acta 484 (2018) 47-51. Recovered from sciencedirect.com.
3. Suresh Kumar, B. and Rajendra Babu, K. (2007). Growth and characterization of doped hippuric acid crystals for NLO devices. Crys. Res. Technol. 42, No. 6, 607-612 (2007). Recovered from onlinelibrary.wiley.com.
4. Bertram, J.E. et al. (2009). Hippuric acid and benzoic acid inhibition of urine derived N_twoOr emissions from soil. Global Change Biology (2009) 15, 2067-2077. Recovered from onlinelibrary.wiley.com.
5. Decharat, S. (2014). Hippuric Acid Levels in Paint Workers at Steel Furniture Manufacturers in Thailand. Safety and Health at Work 5 (2014) 227-233. Recovered from sciencedirect.com.
6. U.S. National Library of Medicine. (2019). Hippuric acid. Recovered from: pubchem.ncbi.nlm.nih.gov.