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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| N-benzoylglycine | |
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| Chemical Name | 2-benzamidoacetic acid |
| Chemical Formula | C9H9NO3 |
| CAS Number | 495-69-2 |
| Chemical Information | HMDB00714 |
| Biochemical Taxonomy |
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| Functional Taxonomy | Not Available |
| Nutritional Taxonomy | Not Available |
| Metabolic Pathways | Not Available |
| Biofluid Location |
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| Tissue Location |
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| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available |
| Diseases / Conditions Related to Nutrition |
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| Other (Monogenic Disorders) | Not Available |
| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available |
| Physiological Processes | Not Available |
| Authors: | |
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Contents |
Introduction
guidelines
Hippuric acid is formed by the conjugation of benzoic acid with glycine. Hippuric acid is the most frequently used biomarker in the biological monitoring of occupational exposure to toluene. This product of solvent biotransformation may be also found in the urine of individuals who have not been exposed to the solvent. A smaller fraction of the absorbed toluene is oxidized to aromatic compounds including ortho-cresol, which is not found significantly in the urine of nonexposed individuals. The concentration of hippuric acid in the urine of individuals exposed to a low toluene concentration does not differ from that of individuals not exposed to the solvent. This has led to the conclusion that hippuric acid should not be utilized in the biological monitoring of occupational exposure to low levels of toluene in the air.
Protein-bound organic acids such as hippuric acid are markedly accumulated in uremic plasma and produce defective protein binding of drugs. (PMID: 9120876, 8734460)
Hippuric acid (also known as n-benzoylglycine or benzoyl amidoacetic acid), is the glycine conjugate of benzoic acid. It is synthesised in the liver and its production is greatly increased following consumption of benzoic acid (e.g. foods containing E210-213) or substances which generate benzoic acid during intermediate metabolism (e.g. foods high in the polyphenols chlorogenic acid, quinic acid and caffeic acid). It appears in variable concentrations in urine and at much lower concentrations in plasma. It is mainly identified on an 1H NMR spectrum at around 7.80-7.86 ppm, although there are other representative peaks.
Biological Function
guidelines
Hippuric acid itself does not have a direct biological function, but its formation in the liver results from detoxification of benzoic acid. Benzoic acid is a naturally occurring crystalline compound, found in a variety of foods. It is also industrially synthesised and it acts as an antiseptic and antifungal agent. Hippuric acid production facilitates an efficient mechanism for the excretion of this otherwise less soluble compound.
Catabolism
guidelines
Formation of hippuric acid results from the conjugation of the amino acid, glycine with the aromatic carboxylic acid, benzoic acid. This reaction takes place in the liver and hippuric acid is the end-point. It is not catabolised but excreted in the urine. Two urinary metabolites of benzoic acid are known, namely hippuric acid and benzoylglucuronic acid. However, in man, rabbits and rats, benzoic acid is almost entirely excreted as hippuric acid. It has been shown that excretion rate is influenced by age and gender, with higher excretion in females and in older age groups (Siqueira ME, 2002)
Diseases / Conditions Related to Nutrition
- Lung Cancer
- Paraquat poisoning
Since it is produced in the liver, the excretion rate of hippuric acid, following the administration of benzoic acid can be used to test liver function. Normal excretion rates are approximately 1.0-1.25 g/day, which is equivalent to 0.7-1.7 g of benzoic acid (normal biofluid concentrations are in the table above in g/l and are sometimes expressed as mmol/mol creatinine). In addition, toluene (also known as methylbenzene or phenylmethane) exposure can be assessed by urinary hippuric acid excretion. Toluene is an aromatic hydrocarbon that is used as a solvent and is a component of paint thinners. It enters the body principally by inhalation but can also enter through soil contamination. Following toluene metabolism, toxicity is caused by epoxides, which cause severe cell damage. Hippuric acid is another toluene metabolite and serves as a biomarker of toxicity. Alcohol consumption and cigarette smoking, both together and individually, are know to interfere with toluene metabolism, but they do not influence hippuric acid excretion in individuals not exposed to toluene (Alvarez-Leite EM, 1999). The presence of diabetes has been shown to increase hippuric acid excretion (Messana I, 1998). Excretion was found to be 511.8 mmol/mol creatinine in diabetics as opposed to 341.0 mmol/mol creatinine in healthy controls. However, hippuric acid excretion was only found to be significantly different in patients with pathological glycated Hb concentrations and glycosuria did not appear to influence excretion levels. This study also reported a high degree of variation in urinary hippuric acid concentrations for all subjects.
Associated decreased protein/metabolite profile
Associated increased protein/metabolite profile
Other (Monogenic) Disorders
guidelines
No genetic diseases are known to exhibit an effect on hippuric acid production
Nutritional Information
guidelines
Dietary intake influences hippuric acid excretion through two main routes. The first is directly, by the consumption of foods containing benzoic acid and the second is indirectly through the metabolism of other plant phenols (mainly chlorogenic acids) by the gut microflora. (However a deficiency of glycine could potentially reduce hippuric acid excretion but this would be very rare as glycine is a nonessential amino acid). Benzoic acid is naturally present in a variety of foods, particularly some fruits and berries, with cranberries being the best example. Cranberries contain so much benzoic acid that they barely spoil. More commonly benzoic acid is used as a food preservative. When added as a preservative, it is labelled as E210-213, benzoic acid or benzoate. Typical products containing this preservative include jams, preserved fruit, pickles, sauces, syrups and beer. Chlorogenic acids are plant phenols formed between trans-cinnamic acids and quinic acid. Chlorogenic acid, an ester of caffeic acid with quinic acid is the most abundant hydroxycinnamic acid found in food and coffee is one of the richest dietary sources. It is estimated that only about 33% of chlorogenic acid is absorbed in the proximal part of the gut (Olthof MR,2001). The remainder reaches the large intestine where it is hydrolysed to caffeic acid and quinic acid by the colonic flora. Following further dehydroxylation, benzoic acid is formed from quinic acid and from 3-hydroxyphenylpropionic acid. The benzoic acid is then conjugated with glycine in the liver and excreted as hippuric acid. It has also been shown that the catechin polymers of black tea, theflavins and therarubigins, are mainly metabolised to hippuric acid (Olthof MR, 2003)(Daykin CA, 2005)(Mulder TP, 2005).On reaching the large intestine, they undergo cleavage by the colonic flora to produce valerolacetates. These are further metabolised to benzoic acid and ultimately excreted as hippuric acid.