MiMeDB: Showing metabocard for Homogentisic acid (MMDBc0047902)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2021-11-23 23:06:06 UTC

Update Date

2024-10-13 14:48:44 UTC

Metabolite ID

MMDBc0047902

Metabolite Identification

Common Name

Homogentisic acid

Description

Homogentisic acid, also known as melanic acid, is an intermediate in the breakdown or catabolism of tyrosine and phenylalanine. It is generated from the compound p-hydroxyphenylpyruvate through the enzyme p-hydroxyphenylpyruvate dehydrogenase. The resulting homogentisic acid is then broken down into 4-maleylacetoacetate via the enzyme homogentisate 1,2-dioxygenase. Homogentisic acid is also found in other organisms. For instance, it can found in Arbutus unedo (strawberry-tree) honey, in the bacterial plant pathogen Xanthomonas campestris as well as in the yeast Yarrowia lipolytica where it is associated with the production of brown pigments. Homogentisic acid can be oxidatively dimerized to form hipposudoric acid, one of the main constituents of the 'blood sweat' of hippopotamuses. When present in sufficiently high levels, homogentisic acid can function as an osteotoxin and a renal toxin. An osteotoxin is a substance that causes damage to bones and/or joints. A renal toxin causes damage to the kidneys. Chronically high levels of homogentisic acid are associated with alkaptonuria (OMIM: 203500 ), an inborn error of metabolism. Alkaptonuria is a rare inherited genetic disorder in which the body cannot process the amino acids phenylalanine and tyrosine. It is caused by a mutation in the enzyme homogentisate 1,2-dioxygenase (EC 1.13.11.5), which leads to an accumulation of homogentisic acid in the blood and tissues. Homogentisic acid and its oxidized form benzoquinone acetic acid are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid (and benzoquinone acetic acid) causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs. More specifically, homogentisic acid can be converted to benzoquinone acetic acid (BQA), and the resulting BQA can be readily converted to polymers that resemble the dark skin pigment melanin. These polymers are deposited in the collagen, a connective tissue protein, of particular tissues such as cartilage. This process is called ochronosis (as the tissue looks ochre); ochronotic tissue is stiffened and unusually brittle, impairing its normal function and causing damage. Homogentisic acid is the primary precursor of melanin synthesis in Vibrio cholerae.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HEADER    PROTEIN                                 03-SEP-20   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   03-SEP-20         0                                  
HETATM    1  C   UNK     0    8667.3328668.205   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8668.6668667.436   0.000  0.00  0.00           C+0
HETATM    3  O   UNK     0    8669.9968668.205   0.000  0.00  0.00           O+0
HETATM    4  O   UNK     0    8668.6668665.899   0.000  0.00  0.00           O+0
HETATM    5  O   UNK     0    8664.6738669.743   0.000  0.00  0.00           O+0
HETATM    6  O   UNK     0    8664.6738663.591   0.000  0.00  0.00           O+0
HETATM    7  C   UNK     0    8666.0048667.437   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0    8664.6708668.207   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0    8663.3368667.437   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0    8663.3368665.897   0.000  0.00  0.00           C+0
HETATM   11  C   UNK     0    8664.6708665.127   0.000  0.00  0.00           C+0
HETATM   12  C   UNK     0    8666.0048665.897   0.000  0.00  0.00           C+0
CONECT    1    2    7                                                       
CONECT    2    1    3    4                                                  
CONECT    3    2                                                            
CONECT    4    2                                                            
CONECT    5    8                                                            
CONECT    6   11                                                            
CONECT    7    8   12    1                                                  
CONECT    8    7    9    5                                                  
CONECT    9    8   10                                                       
CONECT   10    9   11                                                       
CONECT   11   10   12    6                                                  
CONECT   12   11    7                                                       
MASTER        0    0    0    0    0    0    0    0   12    0   24    0
END

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

Molecular Formula

C₈H₈O₄

Average Mass

168.1467

Monoisotopic Mass

168.042258744

IUPAC Name

2-(2,5-dihydroxyphenyl)acetic acid

Traditional Name

homogentisic acid

CAS Registry Number

451-13-8

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 )

Functional Ontology

Not Available

Physical Properties

State

Solid

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	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Not Available

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Blood
Cartilage
Feces
Kidney
Urine

Tissue Locations

Cartilage
Kidney

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192461	4-hydroxyphenylpyruvate dioxygenase	Unknown	P32754	Homo sapiens
MMDBp0192462	Homogentisate 1,2-dioxygenase	Unknown	Q93099	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Alkaptonuria		Association	Human Urine	HMDB	19014543
Alkaptonuria		Association	Human Urine	HMDB	12705346
Alkaptonuria	Increased	Association	Human Urine	HMDB	9529368
Alkaptonuria		Association	Human Urine	HMDB	25956497
Alkaptonuria		Association	Human Urine	HMDB	2914385
Alkaptonuria	Increased	Association	Human Urine	HMDB	12501223
Alkaptonuria		Association	Human Blood	HMDB	2914385
Alkaptonuria	Increased	Association	Human Blood	HMDB	2383921
Eosinophilic esophagitis		Association	Human Urine	HMDB	Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria/Eubacteria	Proteobacteria	134	Human feces; Human sputum; Human ; Human unknown; Human pleural fluid plaque; Turkey	Metabolic reconstruction
Bacteria/Eubacteria	Firmicutes	15	Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Actinobacteria	17	Human feces; Human	Metabolic reconstruction
Bacteria	Actinobacteria	5	Human feces; Human	Metabolic reconstruction
Bacteria/Eubacteria	Bacteroidetes	5	Human feces	Metabolic reconstruction
Bacteria	Proteobacteria	4	Human feces; Human sputum; Human ; Human unknown; Human pleural fluid plaque; Turkey	Metabolic reconstruction
Archaea	Crenarchaeota	1		Metabolic reconstruction
Eukaryota/Fungi	Ascomycota	10	Human feces
Bacteria	nah	1

Exposure Sources

Other Exposures

Source Type	Data Source	Reference
Drugs - Antimicrobial	U.S. Environmental Protection Agency	CompTox
Cosmetics	U.S. Environmental Protection Agency	CompTox
Domestics	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Urine	Detected and Quantified	666.085				umol/mmol creatinine	Infant (0-1 year old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	19014543
Human Urine	Detected and Quantified	2100				umol/mmol creatinine	Infant (0-1 year old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	12705346
Human Urine	Detected and Quantified	4690				umol/mmol creatinine	Children (1 - 13 years old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	12705346
Human Urine	Detected and Quantified	5020				umol/mmol creatinine	Children (1 - 13 years old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	12705346
Human Urine	Detected and Quantified	> 2780				umol/mmol creatinine	Adult (>18 years old)	Both	Alkaptonuria	HMDB	9529368
Human Urine	Detected and Quantified	>1189.438				umol/mmol creatinine	Newborn (0-30 days old)	Male	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	25956497
Human Urine	Detected and Quantified	>1189.438				umol/mmol creatinine	Newborn (0-30 days old)	Male	Alkaptonuria	HMDB	25956497
Human Urine	Detected and Quantified			1570	2220	umol/mmol creatinine	Children (1 - 13 years old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	12705346
Human Urine	Detected and Quantified			1746.67	2500.00	umol/mmol creatinine	Adult (>18 years old)	Not Specified	Alkaptonuria	HMDB	2914385
Human Urine	Detected and Quantified	1819		1134	2504	umol/mmol creatinine	Adult (>18 years old)	Both	Alkaptonuria	HMDB	12501223
Human Urine	Detected and Quantified			1980	2710	umol/mmol creatinine	Children (1 - 13 years old)	Female	Homogentisic Acid Oxidase deficiency (Alkaptonuria)	HMDB	12705346
Human Blood	Detected and Quantified			33.33	46.5	uM	Adult (>18 years old)	Not Specified	Alkaptonuria	HMDB	2914385
Human Blood	Detected and Quantified	35.5		33.0	38.0	uM	Adult (>18 years old)	Both	Alkaptonuria	HMDB	2383921
Human Urine	Detected and Quantified	0.04	0.17			umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	2026685
Human Blood	Detected and Quantified	0.043		0.014	0.071	uM	Adult (>18 years old)	Both	Normal	HMDB	8925087
Human Urine	Detected and Quantified	1.70		0.5	2.8	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	24023812
Human Urine	Detected and Quantified	14.333	9.278			umol/mmol creatinine	Infant (0-1 year old)	Not Specified	Normal	HMDB	12705346
Human Urine	Detected and Quantified	16.593	12.251			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	12705346
Human Urine	Detected and Quantified	16.771	13.262			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	12705346
Human Urine	Detected and Quantified	7.315	4.698			umol/mmol creatinine	Adolescent (13-18 years old)	Not Specified	Normal	HMDB	12705346
Human Urine	Detected and Quantified	7.672	3.330			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	12705346
Human Urine	Detected and Quantified	3.009	1.469			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Urine	Detected and Quantified	1.917	1.061			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Urine	Detected and Quantified	0				umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	HMDB	BC Children's Hospital Biochemical Genetics Lab
Human Cartilage	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Kidney	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Feces	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	19573517
Human Feces	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	20669995
Human Feces	Detected but not Quantified						Adult (>18 years old)	Female	Normal	HMDB	26709303
Human Feces	Detected but not Quantified						Children (6 - 18 years old)	Not Specified	Normal	HMDB	27609529
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

HMDB0000130

DrugBank ID

DB08327

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

METLIN ID

PubChem Compound

PDB ID

Not Available

ChEBI ID

44747

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Venkataseshan VS, Chandra B, Graziano V, Steinlauf P, Marquet E, Irmiere V, Needle MA: Alkaptonuria and renal failure: a case report and review of the literature. Mod Pathol. 1992 Jul;5(4):464-71. [PubMed:1495952 ]
Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. doi: 10.1016/0378-4347(91)80571-s. [PubMed:2026685 ]
Bory C, Boulieu R, Chantin C, Mathieu M: Diagnosis of alcaptonuria: rapid analysis of homogentisic acid by HPLC. Clin Chim Acta. 1990 Jul;189(1):7-11. doi: 10.1016/0009-8981(90)90228-k. [PubMed:2383921 ]
Hegedus ZL, Nayak U: Homogentisic acid and structurally related compounds as intermediates in plasma soluble melanin formation and in tissue toxicities. Arch Int Physiol Biochim Biophys. 1994 May-Jun;102(3):175-81. doi: 10.3109/13813459409007534. [PubMed:8000039 ]
Janocha S, Wolz W, Srsen S, Srsnova K, Montagutelli X, Guenet JL, Grimm T, Kress W, Muller CR: The human gene for alkaptonuria (AKU) maps to chromosome 3q. Genomics. 1994 Jan 1;19(1):5-8. doi: 10.1006/geno.1994.1003. [PubMed:8188241 ]
Deutsch JC, Santhosh-Kumar CR: Quantitation of homogentisic acid in normal human plasma. J Chromatogr B Biomed Appl. 1996 Feb 23;677(1):147-51. doi: 10.1016/0378-4347(95)00442-4. [PubMed:8925087 ]
Concepcion Masip T, Banares Baudet F, Traba ML, Rodriguez de Minon Cifuentes JL: [Alkaptonuria, prostatic calculi, and ectopic ureter]. Actas Urol Esp. 1997 Feb;21(2):167-70. [PubMed:9214216 ]
La Du BN Jr: Are we ready to try to cure alkaptonuria? Am J Hum Genet. 1998 Apr;62(4):765-7. doi: 10.1086/301810. [PubMed:9529368 ]
de Haas V, Carbasius Weber EC, de Klerk JB, Bakker HD, Smit GP, Huijbers WA, Duran M, Poll-The BT: The success of dietary protein restriction in alkaptonuria patients is age-dependent. J Inherit Metab Dis. 1998 Dec;21(8):791-8. doi: 10.1023/a:1005410416482. [PubMed:9870204 ]
Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA: Natural history of alkaptonuria. N Engl J Med. 2002 Dec 26;347(26):2111-21. doi: 10.1056/NEJMoa021736. [PubMed:12501223 ]
Ehongo A, Schrooyen M, Pereleux A: [Important bilateral corneal astigmatism in a case of ocular ochronosis]. Bull Soc Belge Ophtalmol. 2005;(295):17-21. [PubMed:15849984 ]

Showing metabocard for Homogentisic acid (MMDBc0047902)

MOL for #<Metabolite:0x00007f923c03cef8>

3D MOL for #<Metabolite:0x00007f923c03cef8>

3D SDF for #<Metabolite:0x00007f923c03cef8>

3D-SDF for #<Metabolite:0x00007f923c03cef8>

PDB for #<Metabolite:0x00007f923c03cef8>

3D PDB for #<Metabolite:0x00007f923c03cef8>

SMILES for #<Metabolite:0x00007f923c03cef8>

INCHI for #<Metabolite:0x00007f923c03cef8>

Structure for #<Metabolite:0x00007f923c03cef8>

3D Structure for #<Metabolite:0x00007f923c03cef8>