Hippuric acid is an organic compound consistently found in human urine, serving as a normal metabolic byproduct that is excreted daily. The compound is a conjugate of benzoic acid and the amino acid glycine, and its presence reflects the body’s efforts to process and eliminate certain substances. As a simple amide molecule, hippuric acid is highly water-soluble, which facilitates its efficient removal from the body via the kidneys.
How the Body Creates Hippuric Acid
The formation of hippuric acid is a specific metabolic process that functions as a detoxification mechanism. This pathway is primarily carried out in the mitochondria of the liver and, to a lesser extent, the kidneys. The goal is to convert benzoic acid, which can be toxic in high concentrations, into a more benign and easily excreted form.
The process begins when benzoic acid is activated by reacting with coenzyme A (CoA) to form benzoyl-CoA. The enzyme glycine N-acyltransferase then facilitates the final reaction, combining benzoyl-CoA with the amino acid glycine. This conjugation reaction creates the hippuric acid molecule, or N-benzoylglycine.
Converting benzoic acid into hippuric acid significantly increases the compound’s water solubility. This chemical modification is an example of a Phase II detoxification reaction. The efficiency of this pathway depends on the availability of glycine and the proper function of the liver and kidneys.
Dietary and Environmental Sources of Precursors
The benzoic acid needed to create hippuric acid comes from two main sources: the diet and exposure to certain environmental chemicals. A substantial portion of urinary hippuric acid originates from the breakdown of plant-based compounds consumed in the diet. The body absorbs complex molecules called polyphenols, such as flavonoids and catechins, which are abundant in fruits, vegetables, coffee, and tea.
These polyphenols are not directly absorbed in the small intestine but travel to the large intestine where the gut microbiota breaks them down. The bacteria convert these large plant structures into smaller phenolic acids, including benzoic acid. Therefore, a diet rich in berries, plums, whole grains, and beverages like coffee and wine naturally leads to higher levels of hippuric acid excretion.
The second major source of benzoic acid is the industrial solvent toluene. When an individual is exposed to toluene, often in occupational settings like painting or printing, the body metabolizes it through a series of steps. Toluene is oxidized to benzyl alcohol, which is then converted into benzoic acid. This benzoic acid then enters the same conjugation pathway with glycine, producing hippuric acid for excretion.
Interpreting Levels: What Hippuric Acid Measurements Indicate
Measuring hippuric acid in urine offers a non-invasive way to gain insight into an individual’s diet, gut health, and chemical exposure history. High levels can reflect recent, high consumption of polyphenol-rich foods, such as fruits or vegetables. However, the most significant clinical application for elevated levels is monitoring occupational safety, particularly in workers exposed to toluene.
High hippuric acid concentrations are a recognized biomarker for toluene exposure, a common solvent in glues, paints, and thinners. While a standard level is always present, an elevated amount signals that the body has metabolized a significant dose of the solvent. Dietary factors must be considered during interpretation, as they can interfere with the assessment of toluene exposure.
Conversely, low levels of hippuric acid can suggest conditions related to metabolic function or the gut environment. A low reading might indicate a lack of precursor compounds, either from a diet poor in plant-based foods or from an alteration in the gut microbiota that breaks down polyphenols. Low levels may also point to a problem with the detoxification process itself.
The metabolic process requires adequate levels of the amino acid glycine; thus, a glycine deficiency could impair the body’s ability to create hippuric acid. Since conversion takes place in the liver and excretion occurs via the kidneys, low hippuric acid excretion can also be a sign of impaired organ function.