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Record Information
Created at2005-11-16 15:48:42 UTC
Updated at2021-10-07 20:39:52 UTC
NP-MRD IDNP0001257
Secondary Accession NumbersNone
Natural Product Identification
Common Name4-Hydroxyproline
Description4-Hydroxyproline (hydroxyproline or Hyp) is a major component of the protein collagen. Hydroxyproline is produced by hydroxylation of the amino acid proline and is, therefore, a post-translationally modified amino acid. Hydroxyproline and proline play key roles for collagen stability. In particular, they permit the sharp twisting of the collagen helix. Hydroxyproline is found in few proteins other than collagen. The only other mammalian protein which includes hydroxyproline is elastin. For this reason, hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount in tissue or biological samples. Increased serum and urine levels of hydroxyproline have been found in Paget's disease (PMID: 436278 ). Hydroxyproline (Hyp) content in biological fluids is used as a parameter of collagen catabolism, especially bone resorption or tissue degradation. Bedridden and elderly individuals show significantly elevated serum levels of hydroxyproline in comparison to normal, active individuals (PMID: 10706420 ). Elevated levels of urinary hydroxyproline are also indicative of muscle damage (PMID: 21988268 ). Increased reactive oxygen species (ROS) are also known to accelerate collagen degradation. Hydroxyproline levels increase in cases of depression and stress (PMID: 21483218 ). 4-Hydroxyproline is found to be associated with Alzheimer's disease, and also hydroxyprolinemia and iminoglycinuria which are both inborn errors of metabolism. 4-Hydroxyproline is also involved in metabolic disorders such as hyperprolinemia type I, hyperornithinemia with gyrate atrophy (HOGA), L-arginine:Glycine amidinotransferase deficiency, creatine deficiency, and guanidinoacetate methyltransferase deficiency. A deficiency in ascorbic acid can result in impaired hydroxyproline formation (PubChem). Trans-4-Hydroxy-L-proline is a biomarker for the consumption of processed meat.
(2S,4R)-4-Hydroxy-2-pyrrolidinecarboxylic acidChEBI
(2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acidHMDB
4-Hydroxy-2-pyrrolidinecarboxylic acidHMDB
4 HydroxyprolineHMDB
(-)-4-Hydroxy-2-pyrrolidinecarboxylic acidHMDB
4(R)-Hydroxy-2(S)-pyrrolidinecarboxylic acidHMDB
Chemical FormulaC5H9NO3
Average Mass131.1299 Da
Monoisotopic Mass131.05824 Da
IUPAC Name(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
Traditional Namehypro
CAS Registry Number51-35-4
InChI Identifier
Experimental Spectra
Spectrum TypeDescriptionDepositor IDDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, simulated)Varshavi.d262021-10-26View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Varshavi.d262021-10-26View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, simulated)Varshavi.d262021-10-26View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Varshavi.d262021-10-26View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Predicted Spectra
Not Available
Chemical Shift Submissions
Spectrum TypeDescriptionDepositor IDDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, simulated)Varshavi.d262021-08-09View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, simulated)Varshavi.d262021-08-07View Spectrum
Species of Origin
Species NameSourceReference
Afzelia bellaKNApSAcK Database
Allium ampeloprasumFooDB
Anas platyrhynchosFooDB
Anser anserFooDB
Antirrhinum majusLOTUS Database
Arabidopsis thalianaKNApSAcK Database
Arachis hypogaeaFooDB
Bison bisonFooDB
Borago officinalisFooDB
Bos taurusFooDB
Bos taurus X Bison bisonFooDB
Brassica oleracea var. italicaPlant
Bubalus bubalisFooDB
Cannabis sativaCannabisDB
      Not Available
Capra aegagrus hircusFooDB
Castanea sativaKNApSAcK Database
Ceratonia siliquaFooDB
Cervus canadensisFooDB
Chlamydomonas reinhardtiiLOTUS Database
Citrullus lanatusFooDB
Citrus X sinensis (L.) Osbeck (pro. sp.)FooDB
Cocos nuciferaFooDB
Curcuma longaFooDB
Daphnia pulexLOTUS Database
Daucus carotaFooDB
Daucus carota ssp. sativusFooDB
Dromaius novaehollandiaeFooDB
Equus caballusFooDB
Gallus gallusFooDB
Glycine maxFooDB
Hippoglossus hippoglossusFooDB
Homo sapiensLOTUS Database
Lagopus mutaFooDB
Lepus timidusFooDB
Linum usitatissimumFooDB
Melanitta fuscaFooDB
Meleagris gallopavoFooDB
Mus musculusLOTUS Database
Numida meleagrisFooDB
Origanum vulgareFooDB
Origanum X majoricumFooDB
Ovis ariesFooDB
Phaseolus vulgarisFooDB
Phasianus colchicusFooDB
Piper nigrum L.FooDB
Prunus domesticaLOTUS Database
Salmo salarFooDB
Santalum albumKNApSAcK Database
Solanum tuberosumFooDB
Struthio camelusFooDB
Sus scrofaFooDB
Sus scrofa domesticaFooDB
Syzygium aromaticumFooDB
Vicia fabaKNApSAcK Database
Zea mays L.FooDB
Chemical Taxonomy
Description Belongs to the class of organic compounds known as proline and derivatives. Proline and derivatives are compounds containing proline or a derivative thereof resulting from reaction of proline 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 ParentProline and derivatives
Alternative Parents
  • Proline or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Pyrrolidine carboxylic acid
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine
  • 1,2-aminoalcohol
  • Amino acid
  • Secondary alcohol
  • Carboxylic acid
  • Secondary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Secondary amine
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Amine
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Physical Properties
Experimental Properties
Melting Point274 - 275 °CNot Available
Boiling Point186.13 °C. @ 760.00 mm Hg (est)The Good Scents Company Information System
Water Solubility361 mg/mL at 25 °CNot Available
LogP-3.17Hansch CH, Leo A and Hoekman DH. "Exploring QSAR: Hydrophobic, Electronic, and Steric Constraints. Volume 1" ACS Publications (1995).
Predicted Properties
Water Solubility492 g/LALOGPS
pKa (Strongest Acidic)1.64ChemAxon
pKa (Strongest Basic)10.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area69.56 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity29.38 m³·mol⁻¹ChemAxon
Polarizability12.29 ųChemAxon
Number of Rings1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
DrugBank IDDB08847
Phenol Explorer Compound IDNot Available
FoodDB IDFDB013511
KNApSAcK IDC00001370
Chemspider ID5605
KEGG Compound IDC01157
BiGG ID36935
Wikipedia LinkHydroxyproline
PubChem Compound5810
PDB IDNot Available
ChEBI ID18095
Good Scents IDrw1510101
General References
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  16. Lindblad WJ, Diegelmann RF: Quantitation of hydroxyproline isomers in acid hydrolysates by high-performance liquid chromatography. Anal Biochem. 1984 May 1;138(2):390-5. [PubMed:6742416 ]
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