Homogentisic Acid

2,5-DIHYDROXYPHENYLACETIC ACID · 2-(2,5-dihydroxyphenyl)acetic acid · alcapton · Melanic acid · homogentisicaci · Homogentisic acid · Homogentisinic acid · HOMOGENTISIC ACID(RG)

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Identifiers & Physical Properties

CAS No.	451-13-8
Molecular formula	C8H8O4
Average molar mass	168.15 g/mol
Monoisotopic mass	168.04225874 g/mol
SMILES	O=C(O)Cc1cc(O)ccc1O
InChIKey	IGMNYECMUMZDDF-UHFFFAOYSA-N
PubChem CID	780
ChEBI	CHEBI:44747
EC No.	207-192-7
DTXSID	DTXSID1060005

Chemical & Physical Properties

XLogP	0.5
Topological polar surface area	77.8
Hydrogen bond donors	3
Hydrogen bond acceptors	4
Rotatable bonds	2
Heavy atoms	12
Formal charge	0
Complexity	168
Chemical classes	Other Classes -> Organic Acids
Drugs	Pharmaceuticals -> Metabolite of DiclofenacPharmaceuticals -> Listed in ZINC15
LogP (partition coefficient)	0.86
Solubility	850 mg/mL at 25 °CSoluble in methanol.very faint turbidity
Melting point	153 °C150-152 °C (lit.)
Vapor pressure	0.00000082 [mmHg]
Physical Description	Beige crystalline solid[Sigma-Aldrich MSDS]
Collision Cross Section	132.4 Å² [M-H]- [CCS Type: DTMethod: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]135.9 Å² [M+H-H2O]+ [CCS Type: DTMethod: single field calibrated with Agilent tune mix (Agilent)]132.7 Å² [M-H]-
Boiling point	257.07°C (rough estimate)
Density	1.3037 (rough estimate)
Refractive index	1.5090 (estimate)
Storage conditions	2-8°C
pKa (acidity coefficient)	4.4(at 25℃)
Physical state	crystalline
Color	off-white to tan
Merck	14,4737
BRN	2692860
Major applications	food and beverages
InChI	1S/C8H8O4/c9-6-1-2-7(10)5(3-6)4-8(11)12/h1-3,9-10H,4H2,(H,11,12)
InChIKey	IGMNYECMUMZDDF-UHFFFAOYSA-N
SMILES	OC(=O)Cc1cc(O)ccc1O
LogP (partition coefficient)	0.860
CAS DataBase Reference	451-13-8(CAS DataBase Reference)
FDA UNII	NP8UE6VF08
EPA Substance Registry System	Benzeneacetic acid, 2,5-dihydroxy- (451-13-8)
UNSPSC Code	41116107
NACRES	NA.24
GHS pictogram	GHS07
Signal word	Warning
GHS hazard statements	H315-H319-H335
GHS precautionary statements	P280a-P304+P340-P405-P501a-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P261-P305+P351+P338
Hazard symbols	Xi
Risk statements (R)	36/37/38
Safety statements (S)	26-36
Water hazard class (WGK)	3
RTECS number	AH0589000
TSCA inventory status	TSCA listed
Customs code	29182900
Storage class	13 - Non Combustible Solids

Safety & Regulations

GHS classification	WarningH315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazards summary	Causes changes in urine composition in 5-day intermittent intraperitoneal studies of rats[RTECS] A skin and strong eye irritant[Sigma-Aldrich MSDS]
Hazard Classes and Categories	Skin Irrit. 2 (100%)
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.
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.

Applications & Uses

Uses

An intermediate in the metabolism of tyrosine and phenylalanine. Occurs in plants and in the urine of alkaptonurics.

Uses

Homogentisic acid may be used as an analytical reference standard for the quantification of the analyte in the following:Urine matrices using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS).Strawberry tree honey samples using reversed phase-high performance liquid chromatography (RP-HPLC) and ion chromatography (IC).It may also be used as an internal standard for the determination of ascorbic acid (AA) and uric acid (UA) in human plasma samples using high-pressure liquid chromatography–electrochemical detection (HPLC–ECD).

General Description

Homogentisic acid (HGA) is an intermediate formed during the catabolism of phenylalanine and tyrosine. Alkaptonuria, a metabolic disorder, is characterized by high levels of HGA in serum and urine due to the deficiency of the enzyme homogentisic acid oxidase, which is involved in the degradation of HGA.