ChemFOnt: Showing chemical card for Hawkinsin (CFc000001585)

Record Information

Version

1.0

Creation Date

2022-08-28 10:25:12 UTC

Update Date

2022-09-13 18:46:15 UTC

Chemfont ID

CFc000001585

Molecule Identification

Common Name

Hawkinsin

Definition

Hawkinsin is a sulfur amino acid identified as (2-L-cystein-S-yl-1,4-dihydroxycyclohex-5-en-1-yl)acetic acid. It is a reactive byproduct of abnormal tyrosine metabolism. Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme leads to an inborn error of metabolism called tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid but is unable to convert this intermediate to homogentisate (PMID: 11073718 ). The intermediate then spontaneously reacts with glutathione to form hawkinsin. Chronically high levels of hawkinsin are associated with hawkinsinuria (characterized by the inability to break down the amino acid tyrosine). Patients with hawkinsinuria excrete hawkinsin in their urine throughout their life. The features of this condition usually appear around the time infants are weaned off breast milk and begin to use formula. The signs and symptoms may include the following: failure to gain weight and grow at the expected rate (failure to thrive), abnormally high acid levels in the blood (acidosis), and fine or sparse hair. Hawkinsin is 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. Hawkinsin 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 untreated hawkinsinuria. 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
(2-L-Cystein-S-yl-1,4-dihydroxycyclohex-5-en-1- yl)acetic acid	HMDB
2-Amino-3-{[2-(carboxymethyl)-2,5-dihydroxycyclohex-3-en-1-yl]sulfanyl}propanoate	HMDB
2-Amino-3-{[2-(carboxymethyl)-2,5-dihydroxycyclohex-3-en-1-yl]sulphanyl}propanoate	HMDB
2-Amino-3-{[2-(carboxymethyl)-2,5-dihydroxycyclohex-3-en-1-yl]sulphanyl}propanoic acid	HMDB
Hawkinsin	MeSH

Chemical Formula

C₁₁H₁₇NO₆S

Average Molecular Weight

291.321

Monoisotopic Molecular Weight

291.077657971

IUPAC Name

2-amino-3-{[2-(carboxymethyl)-2,5-dihydroxycyclohex-3-en-1-yl]sulfanyl}propanoic acid

Traditional Name

hawkinsin

CAS Registry Number

63224-90-8

SMILES

NC(CSC1CC(O)C=CC1(O)CC(O)=O)C(O)=O

InChI Identifier

InChI=1S/C11H17NO6S/c12-7(10(16)17)5-19-8-3-6(13)1-2-11(8,18)4-9(14)15/h1-2,6-8,13,18H,3-5,12H2,(H,14,15)(H,16,17)

InChI Key

SPXVLTDISXZSFM-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as cysteine and derivatives. Cysteine and derivatives are compounds containing cysteine or a derivative thereof resulting from reaction of cysteine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Cysteine and derivatives

Alternative Parents

Substituents

Cysteine or derivatives
Alpha-amino acid
Hydroxy fatty acid
Thia fatty acid
Dicarboxylic acid or derivatives
Fatty acyl
Tertiary alcohol
Amino acid
Secondary alcohol
Carboxylic acid
Dialkylthioether
Sulfenyl compound
Thioether
Organic oxide
Organopnictogen compound
Primary amine
Organosulfur compound
Organooxygen compound
Organonitrogen compound
Primary aliphatic amine
Organic oxygen compound
Alcohol
Carbonyl group
Amine
Organic nitrogen compound
Hydrocarbon derivative
Aliphatic homomonocyclic compound

Molecular Framework

Aliphatic homomonocyclic compounds

External Descriptors

Not Available

Functional Ontology

Not Available

Urine (PMID: 10412819)

Cellular substructure

Cytoplasm (HMDB: HMDB0002354)
Membrane (HMDB: HMDB0002354)

Source

Endogenous

Endogenous (HMDB: HMDB0002354)

Pheasant (FooDB: FOOD00430)
Squab (FooDB: FOOD00481)
Turkey (FooDB: FOOD00494)
Quail (FooDB: FOOD00541)
Anatidae (FooDB: FOOD00576)
Rock ptarmigan (FooDB: FOOD00597)
Columbidae (Dove, Pigeon) (FooDB: FOOD00610)
Chicken (FooDB: FOOD00329)
Mallard duck (FooDB: FOOD00353)
Emu (FooDB: FOOD00360)
Greylag goose (FooDB: FOOD00368)
Guinea hen (FooDB: FOOD00373)
Ostrich (FooDB: FOOD00422)
Velvet duck (FooDB: FOOD00427)

Lagomorph

Ovis

Sheep (Mutton, Lamb) (FooDB: FOOD00473)

Bovine

Venison

Deer (FooDB: FOOD00524)
Mule deer (FooDB: FOOD00348)
Elk (FooDB: FOOD00359)

Caprae

Domestic goat (FooDB: FOOD00529)

Swine

Domestic pig (FooDB: FOOD00536)
Wild boar (FooDB: FOOD00307)

Equine

Horse (FooDB: FOOD00378)

Process

Naturally occurring process

Biological process

Biochemical pathway

Disease pathway

Hawkinsinuria (HMDB: HMDB0002354)

Role

Indirect biological role

Metabotoxin

Metabotoxin (HMDB: HMDB0002354)

Physical Properties

Predicted Properties

Property	Value	Source
Water Solubility	11.4 g/L	ALOGPS
logP	-3.2	ALOGPS
logP	-3.9	ChemAxon
logS	-1.4	ALOGPS
pKa (Strongest Acidic)	1.94	ChemAxon
pKa (Strongest Basic)	9.13	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	7	ChemAxon
Hydrogen Donor Count	5	ChemAxon
Polar Surface Area	141.08 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	68.53 m³·mol⁻¹	ChemAxon
Polarizability	27.83 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon