ContaminantDB: Homogentisic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References XML

Record Information

Version

1.0

Creation Date

2014-08-29 06:15:36 UTC

Update Date

2026-04-03 00:35:15 UTC

Accession Number

CHEM003247

Identification

Common Name

Homogentisic acid

Class

Small Molecule

Description

Homogentisic acid is an intermediate of the metabolic breakdown of tyrosine and phenylalanine; it occurs in the urine in cases of alkaptonuria. (OMIN 203500) Homogentisic acid is the primary precursor of melanin synthesis in Vibrio cholerae.

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Feces
HMDB Contaminants - Urine
T3DB toxins

Contaminant Type

Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
2,5-Dihydroxyphenylacetic acid	ChEBI
2-(3,6-DIHYDROXYPHENYL)acetIC ACID	ChEBI
2,5-Dihydroxyphenylacetate	Kegg
2-(3,6-DIHYDROXYPHENYL)acetate	Generator
Homogentisate	Generator
(2,5-Dihydroxyphenyl)-acetate	HMDB
(2,5-Dihydroxyphenyl)-acetic acid	HMDB
2,5-Dihydroxy-a-toluate	HMDB
2,5-Dihydroxy-a-toluic acid	HMDB
2,5-Dihydroxy-alpha-toluate	HMDB
2,5-Dihydroxy-alpha-toluic acid	HMDB
2,5-Dihydroxy-benzeneacetate	HMDB
2,5-Dihydroxy-benzeneacetic acid	HMDB
Alcapton	HMDB
Homogentisate acid	HMDB
Homogentisinate	HMDB
Homogentisinic acid	HMDB
Melanic acid	HMDB
Acid, homogentisic	HMDB

Chemical Formula

C₈H₈O₄

Average Molecular Mass

168.147 g/mol

Monoisotopic Mass

168.042 g/mol

CAS Registry Number

451-13-8

IUPAC Name

2-(2,5-dihydroxyphenyl)acetic acid

Traditional Name

homogentisic acid

SMILES

OC(=O)CC1=C(O)C=CC(O)=C1

InChI Identifier

InChI=1S/C8H8O4/c9-6-1-2-7(10)5(3-6)4-8(11)12/h1-3,9-10H,4H2,(H,11,12)

InChI Key

IGMNYECMUMZDDF-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as 2(hydroxyphenyl)acetic acids. These are phenylacetic acids that carry a hydroxyl group at the 2-position.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenylacetic acids

Direct Parent

2(hydroxyphenyl)acetic acids

Alternative Parents

Substituents

2(hydroxyphenyl)acetic acid
Hydroquinone
1-hydroxy-2-unsubstituted benzenoid
Phenol
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

hydroquinones (CHEBI:44747 )
dihydroxyphenylacetic acid (CHEBI:44747 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Cartilage
Connective Tissue
Kidney

Pathways

Name	SMPDB Link	KEGG Link
Phenylalanine and Tyrosine Metabolism	SMP00008	map00360
Tyrosine Metabolism	SMP00006	map00350
Alkaptonuria	SMP00169	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	153°C
Boiling Point	Not Available
Solubility	850 mg/mL at 25°C

Predicted Properties

Property	Value	Source
Water Solubility	8.1 g/L	ALOGPS
logP	0.81	ALOGPS
logP	1	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	3.57	ChemAxon
pKa (Strongest Basic)	-5.9	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	77.76 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	41.33 m³·mol⁻¹	ChemAxon
Polarizability	15.57 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000t-0945000000-2f4b9ef9c9ee6e7cd1ed	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-0016-3955000000-1cdc64ab3032ff29df29	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a5c-0679000000-97890865f85a79efa2e6	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000t-0945000000-2f4b9ef9c9ee6e7cd1ed	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0016-3955000000-1cdc64ab3032ff29df29	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-0944000000-fd48cc27da661ce24833	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00di-4900000000-ea40fc8d43156151710c	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-014i-5093000000-c342ba08a9bff049fc1c	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_3_1) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-00di-0900000000-9c395aa569b4b54f8681	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-00xs-9500000000-ab92286f0d5bc843814b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-014l-9000000000-35740a40f4fdf3e84c3c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-014i-0900000000-f4eba60d63bd99e18b8b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-00di-0900000000-12e330dc18f0b128b961	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-00di-0900000000-4bd53b0472edd31e8609	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-00di-0900000000-7121173193a9ba3751a4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-00di-1900000000-04eca21bf25c671b8b6e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-00di-0900000000-780d3740762c2ff89d9a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-014i-0900000000-f4eba60d63bd99e18b8b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00di-0900000000-12e330dc18f0b128b961	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00di-0900000000-4bd53b0472edd31e8609	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00di-0900000000-7121173193a9ba3751a4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00di-1900000000-04eca21bf25c671b8b6e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-00di-0900000000-9c85164306514c6d4c4b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-00di-0900000000-867a4e32ba2d14fd0aad	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0900000000-ac8e05a9300b51b24e77	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-00di-1900000000-eeb664cef1197d609735	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-00di-0900000000-1d890267ec7f3a5843b3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0gb9-0900000000-a650bbb95019f3305d03	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00di-1900000000-94f13b2c7b9726353701	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-05tf-9300000000-968a6390a00dcd77e566	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01b9-0900000000-0f9d5926d702af7d4d63	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01b9-1900000000-7f257033d3b1952b3c27	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9800000000-bbcb0f0d7348cd1663b1	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,1H] 2D NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Extremely high levels of homogentisic acid are found in patients with the inborn error of metabolism (IEM) called Alkaptonuria. Homogentisic acid spontaneously undergoes oxidation into benzoquinone acetic acid (BQA), which polymerizes forming plasma soluble melanins (PSM). The PSM darkens many tissues (ochronosis - as the tissue looks like ochre), and produces widespread degenerative changes in cartilage and other connective tissues, joints, blood vessels, heart valves and the kidneys. Ochronotic tissue is stiff and unusually brittle. The accumulation of PSM in chondrocytes (the cells that form cartilage) leads to profound alterations in the levels of proteins involved in cell defense, protein folding, and cell organization. An increased post-translational oxidation of proteins, which also involved high molecular weight protein aggregates, has been found to be particularly evident in chondrocytes from patients with alkaptonuria.

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

Homogentisic acid is only toxic under chronic exposure. One of the first symptoms of alkaptonuria is darkening of urine on standing (due to the oxidation of homogentisic acid). In most pediatric patients, darkening of urine is the only feature suggesting alkaptonuria. Most patients are usually asymptomatic until age 30. Scleral pigmentation usually starts around age 30. Skin pigmentation becomes obvious by the time patients reach age 40. One of the first sites to be affected is the ear cartilage. There may be discoloration of the forehead, cheeks, axilla, genitalia, palms, nails and soles. Ochronotic arthropathy starts around the 4th decade. Weight-bearing joints like the knees and the intervertebral joints in the spine, as well as the shoulder joints, are involved, with narrowing of joint spaces and disc calcifications. Arthritis is the only disabling effect of this condition and occurs in almost all patients as age advances. Ochronotic arthropathy can be so severe as to require total joint replacement. Pigment deposits can be seen in the larynx, tonsils, esophagus, dura mater, eardrums, trachea, and bronchi. Aortic or mitral valvulitis, calcification of coronary arteries and atherosclerotic plaques are seen after the age of 50 years.

Symptoms

Not Available

Treatment

Apart from treatment of the complications (such as pain relief using NSAIDs and joint replacement for the cartilage damage), vitamin C has been used to reduce the ochronosis and lowering of the homogentisic acid levels may be attempted with a low-protein diet. Recently the drug nitisinone has been found to suppress homogentisic acid production. Nitrisinone inhibits the enzyme, 4-hydroxyphenylpyruvate dioxygenase, responsible for converting tyrosine to homogentisic acid, thereby blocking the production and accumulation of homogentisic acid. Nitisinone treatment has been shown to cause a 95% reduction in plasma and urinary homogentisic acid.

Concentrations

Not Available

External Links

DrugBank ID

DB08327

HMDB ID

HMDB0000130

FooDB ID

FDB030907

Phenol Explorer ID

Not Available

KNApSAcK ID