Hawkinsin (T3D4372)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationXML
Record Information
Version2.0
Creation Date2014-08-29 06:36:15 UTC
Update Date2018-03-21 17:46:19 UTC
Accession NumberT3D4372
Identification
Common NameHawkinsin
ClassSmall Molecule
DescriptionHawkinsin 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.
Compound Type
  • Amine
  • Animal Toxin
  • Ether
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
6-((2-Amino-2-carboxyethyl)thio)-1,4-dihydroxy-2-cyclohexene-1-acetic acid
S-[2-(Carboxymethyl)-2,5-dihydroxy-3-cyclohexen-1-yl]cysteine
Chemical FormulaC11H17NO6S
Average Molecular Mass291.321 g/mol
Monoisotopic Mass291.078 g/mol
CAS Registry Number63224-90-8
IUPAC Name2-amino-3-{[2-(carboxymethyl)-2,5-dihydroxycyclohex-3-en-1-yl]sulfanyl}propanoic acid
Traditional Namehawkinsin
SMILESNC(CSC1CC(O)C=CC1(O)CC(O)=O)C(O)=O
InChI IdentifierInChI=1/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 KeyInChIKey=SPXVLTDISXZSFM-UHFFFAOYNA-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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentCysteine 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 FrameworkAliphatic homomonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
HawkinsinuriaSMP00190 Not Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility11.4 g/LALOGPS
logP-3.2ALOGPS
logP-3.9ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)9.13ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area141.08 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity68.53 m³·mol⁻¹ChemAxon
Polarizability27.83 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-9580000000-4b40e1d101b785a5dd342017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (4 TMS) - 70eV, Positivesplash10-03xr-4222590000-00bbdf636168538d532b2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03l9-1190000000-206d29f4a7cff85fffa32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-009j-5970000000-7486127e0c33383435152016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0079-3910000000-79b2a177b9554ba4e6332016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0097-1290000000-3302da5c9548345e6cb62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0k9i-2940000000-ac9dc52f5dfc532dcc2a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000i-9500000000-d77a0aa1fb9e315dd6a52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0290000000-55ebb1293acd072b4f5a2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-059i-2930000000-6e7be00f88b7169d16ef2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-4910000000-ecd4104261d2ab7a630a2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00e9-9520000000-707174d2daa4d39cff732021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-1900000000-76e4520868ce9296de722021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052o-9600000000-f2e0b234935cb35086062021-09-23View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of hawkinsin are associated with Hawkinsinuria.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB02354
PubChem Compound ID173909
ChEMBL IDNot Available
ChemSpider ID151775
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F: Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Mol Genet Metab. 2000 Nov;71(3):506-10. [11073718 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available