What molecule am I?
Homogentisic acid is a carboxylic acid with an aromatic ring functionalized by two hydroxyl groups. The compound was known by 1901, when Kennedy J. P. Orton at St. Bartholomew’s Hospital (London) reported its use as a substrate in an article titled “The benzoylation of fatty acids in the presence of ammonia”.
In the early 20th century, there were reports of homogentisic acid in the urine of individuals with alkaptonuria, a genetic disease that can lead to osteoarthritis, kidney stones, and heart valve damage. A 1909 account by Oskar Adler at the German University in Prague described a method for isolating the compound from urine.
Homogentisic acid occurs in multiple natural sources. In 1994, Paul H. Goodwin* and Coralie. R. Sopher at the University of Guelph (ON) reported that a brown pigment produced by some strains of the bacterial pathogen Xanthomonas campestris was the result of the secretion and subsequent oxidation of homogentisic acid. Five years after that, homogentisic acid was discovered in the honey of the strawberry tree (Arbutus unedo), as reported by Paolo Cabras at the University of Cagliari (Italy) and colleagues there and at other Italian institutions.
Homogentisic acid is formed in organisms during the breakdown of the amino acids phenylalanine1 and tyrosine2. In patients with alkaptonuria, homogentisic acid builds up because of a deficiency in the enzyme homogentisate 1,2-dioxygenase, which cleaves the aromatic ring and converts the acid to 4-maleylacetoacetic acid3. David E. Timm and coauthors stated that “alkaptonuria was the first human disease shown to be inherited as a recessive Mendelian trait”.
An early laboratory synthesis of homogentisic acid from 2,5-dihydroxymandelic acid4 or 2,5-dihydroxyphenylglyoxylic acid5 was reported in 1907; but improved syntheses were reported much later, including that of Lynn DeForrest Abbott, Jr., and J. Doyle Smith at the Medical College of Virginia (Richmond) in 1949, who prepared it in three steps from 1,4-dimethoxybenzene6.
Homogentisic acid’s importance lies in medicinal and biochemical research. It has no commercial uses.
1. CAS Reg. No. 63-91-2.
2. CAS Reg. No. 60-18-4.
3. CAS Reg. No.5698-52-2.
4. CAS Reg. No. 90111-47-0.
5. CAS Reg. No. 10385-70-3.
6. CAS Reg. No. 150-78-7.
Homogentisic acid hazard information
| Hazard class* | GHS code and hazard statement | |
|---|---|---|
| Skin corrosion/irritation, category 2 | H315—Causes skin irritation |  |
| Serious eye damage/eye irritation, category 2A | H319—Causes serious eye irritation | |
| Specific target organ toxicity, single exposure, respiratory tract irritation, category 3 | H335—May cause respiratory irritation | |
*Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms.
Molecules in the News
Mitragynine1 was the Molecule of the Week for February 27, 2017. It is the major alkaloid found in the leaves of the Asian plant Mitragyna speciosa. The leaves, known familiarly as kratom, have been used in traditional medicine for centuries; but in 2016, its opiate-like properties caused the US Drug Enforcement Administration to classify kratom and mitragynine as Schedule I substances. At the time, this move was criticized by scientists who were seeking to develop useful drugs from mitragynine.
Now there is a revival of interest in kratom/mitragynine. On June 19, Karen Garcia at the Los Angeles Times wrote that the National Institutes of Health (Bethesda, MD) and researchers at the University of Florida (Gainesville) plan to begin clinical trials on mitragynine to evaluate its potential as a treatment for opioid use disorder. In contrast, Garcia described how kratom and another of its components, 7-hydroxymitragynine2 (aka 7-OH), have been the subject of a crackdown by the California Department of Public Health, which has seized >$5 million worth of the substances.
1. CAS Reg. No. 4098-40-2.
2. CAS Reg. No. 174418-82-7.
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Homogentisic acid fast facts
| CAS Reg. No. | 451-13-8 |
| SciFinder name | Benzeneacetic acid, 2,5-dihydroxy- |
| Empirical formula | C8H8O4 |
| Molar mass | 168.15 g/mol |
| Appearance | White to off-white crystals |
| Melting point | 150–152 °C |
| Water solubility | 850 g/L (25 °C) |
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