ChemFOnt: Showing chemical card for 3-Hydroxymethylglutaric acid (CFc000000256)

Record Information

Version

1.0

Creation Date

2022-08-28 10:25:12 UTC

Update Date

2022-09-13 18:44:36 UTC

Chemfont ID

CFc000000256

Molecule Identification

Common Name

3-Hydroxymethylglutaric acid

Definition

3-Hydroxymethylglutaric acid is an "off-product" intermediate in the leucine degradation process. It is produced by defective or inefficient versions of 3-hydroxy-3-methylglutaryl-CoA lyase, an enzyme that normally catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA to acetyl-CoA and acetoacetate. If this enzyme is defective, 3-hydroxy-3-methylglutaryl-CoA will accumulate in the mitochondria. Increased concentrations of 3-hydroxy-3-methylglutaryl-CoA can lead to a disruption of the esterified CoA:free CoA ratio and ultimately to mitochondrial toxicity. Detoxification of these CoA end products occurs via the transfer of the 3-hydroxymethylglutaryl moiety to carnitine, forming 3-hydroxymethylglutaric-carnitine, which is then transferred across the inner mitochondrial membrane where 3-hydroxymethylglutaric acid is released as the free acid. 3-Hydroxymethylglutaric acid has been found to accumulate in the urine of patients affected by 3-Hydroxy-3-methylglutaric aciduria, a rare inborn error of metabolism (OMIM: 246450 ). 3-Hydroxy-3-methylglutaric aciduria is caused by significantly reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4), the enzyme that catalyzes the final step of leucine degradation. This enzyme also plays a key role in ketone body formation. The profile of urinary organic acids for individuals with 3-hydroxy-3-methylglutaric aciduria is different from that of the other identified defects of leucine degradation, such as maple syrup urine disease (OMIM: 248600 ), isovaleric acidemia (OMIM: 243500 ), and methylcrotonylglycinemia (OMIM: 210200 ). The urinary organic acid profile of 3-hydroxy-3-methylglutaric aciduria includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic, and 3-methylglutaric acids (PMID: 10916782 , 9658458 , 3063529 ). Clinical manifestations of 3-hydroxy-3-methylglutaric aciduria include hepatomegaly, lethargy, coma, and apnea. Biochemically, there is a characteristic absence of ketosis with hypoglycemia, acidosis, hypertransaminasemia, and variable hyperammonemia. Therefore, when present in sufficiently high concentrations, 3-hydroxymethylglutaric acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. As noted above, chronically high levels of 3-hydroxymethylglutaric acid are associated with the inborn error of metabolism 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 3-Hydroxymethylglutaric acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(S)-3-Hydroxy-3-methylglutaric acid	ChEBI
(S)-Meglutol	ChEBI
3-HYDROXY-3-methyl-glutarIC ACID	ChEBI
3-Hydroxy-3-methylpentanedioic acid	ChEBI
beta-Hydroxy-beta-methylglutaric acid	ChEBI
Dicrotalic acid	ChEBI
Meglutol	ChEBI
Meglutolum	ChEBI
3-Hydorxy-3-methylglutaric acid	Kegg
(S)-3-Hydroxy-3-methylglutarate	Generator
3-HYDROXY-3-methyl-glutarate	Generator
3-Hydroxy-3-methylpentanedioate	Generator
b-Hydroxy-b-methylglutarate	Generator
b-Hydroxy-b-methylglutaric acid	Generator
beta-Hydroxy-beta-methylglutarate	Generator
Β-hydroxy-β-methylglutarate	Generator
Β-hydroxy-β-methylglutaric acid	Generator
Dicrotalate	Generator
3-Hydorxy-3-methylglutarate	Generator
3-Hydroxymethylglutarate	Generator
3-Hydroxy-3-methylglutarate	HMDB
3-Hydroxy-3-methylglutaric acid	HMDB
3-Methyl-3-hydroxyglutarate	HMDB
3-Methyl-3-hydroxyglutaric acid	HMDB
CB 337	HMDB
3 Hydroxy 3 methylpentanedioic acid	HMDB
Acid, 3-hydroxy-3-methylglutaric	HMDB
Acid, 3-hydroxy-3-methylpentanedioic	HMDB
beta Hydroxy beta methylglutarate	HMDB
3 Hydroxy 3 methylglutaric acid	HMDB
3-Methyl-3-hydroxypentanedioate	HMDB
3-Methyl-3-hydroxypentanedioic acid	HMDB
HMG	HMDB
HMGA	HMDB
Lipoglutaren	HMDB
Medroglutarate	HMDB
Medroglutaric acid	HMDB

Chemical Formula

C₆H₁₀O₅

Average Molecular Weight

162.1406

Monoisotopic Molecular Weight

162.05282343

IUPAC Name

3-hydroxy-3-methylpentanedioic acid

Traditional Name

meglutol

CAS Registry Number

503-49-1

SMILES

CC(O)(CC(O)=O)CC(O)=O

InChI Identifier

InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)

InChI Key

NPOAOTPXWNWTSH-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty acids and conjugates

Direct Parent

Hydroxy fatty acids

Alternative Parents

Substituents

Methyl-branched fatty acid
Short-chain hydroxy acid
Hydroxy fatty acid
Branched fatty acid
Dicarboxylic acid or derivatives
Tertiary alcohol
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Alcohol
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

tertiary alcohol (CHEBI:16831 )
dicarboxylic acid (CHEBI:16831 )
3-hydroxy carboxylic acid (CHEBI:16831 )

Functional Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 32966057)
Saliva (HMDB: HMDB0000355)

Organ

Placenta (HMDB: HMDB0000355)

Excreta

Biofluid or Excreta

Urine (PMID: 8087979)
Feces (PMID: 27543620)

Cellular substructure

Cytoplasm (HMDB: HMDB0000355)
Extracellular (HMDB: HMDB0000355)

Source

Exogenous

Exogenous (HMDB: HMDB0000355)

Food

Herb and spice

Oilseed crop

Flaxseed (FooDB: FOOD00101)

Endogenous

Endogenous (HMDB: HMDB0000355)

Process

Naturally occurring process

Biological process

Biochemical pathway

Disease pathway

3-Hydroxy-3-methylglutaryl-CoA Lyase Deficiency (HMDB: HMDB0000355)

EC 1.1.1.34/EC 1.1.1.88 (hydroxymethylglutaryl-CoA reductase) inhibitor (HMDB: HMDB0000355)

Industrial application

Pharmaceutical industry

Anticholesteremic drug (HMDB: HMDB0000355)

Biomarker

Eosinophilic esophagitis (MarkerDB: MDB00000152)

Physical Properties

Predicted Properties

Property	Value	Source
Water Solubility	275 g/L	ALOGPS
logP	-0.88	ALOGPS
logP	-0.75	ChemAxon
logS	0.23	ALOGPS
pKa (Strongest Acidic)	3.68	ChemAxon
pKa (Strongest Basic)	-3	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	94.83 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	34.14 m³·mol⁻¹	ChemAxon
Polarizability	14.55 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

External Links

HMDB ID

HMDB0000355

DrugBank ID

DB04377

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

5344

PubChem Compound

1662

PDB ID

Not Available

ChEBI ID

16831

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Klosterman, Harold J.; Smith, F. The isolation of b-hydroxy-b-methylglutaric acid from the seed of flax (Linum usitatissimum). Journal of the American Chemical Society (1954), 76 1229-30.

Showing chemical card for 3-Hydroxymethylglutaric acid (CFc000000256)

MOL for CFc000000256 (3-Hydroxymethylglutaric acid)

3D MOL for CFc000000256 (3-Hydroxymethylglutaric acid)

3D SDF for CFc000000256 (3-Hydroxymethylglutaric acid)

3D-SDF for CFc000000256 (3-Hydroxymethylglutaric acid)

PDB for CFc000000256 (3-Hydroxymethylglutaric acid)

3D PDB for CFc000000256 (3-Hydroxymethylglutaric acid)

SMILES for CFc000000256 (3-Hydroxymethylglutaric acid)

INCHI for CFc000000256 (3-Hydroxymethylglutaric acid)

Structure for CFc000000256 (3-Hydroxymethylglutaric acid)

3D Structure for CFc000000256 (3-Hydroxymethylglutaric acid)