You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2007-04-12 21:28:41 UTC
Update Date2016-02-11 01:07:22 UTC
HMDB IDHMDB06055
Secondary Accession NumbersNone
Metabolite Identification
Common Name4-Hydroxy-L-proline
Description4-Hydroxy-L-proline is a hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. (PubChem CID:69248).
Structure
Thumb
Synonyms
ValueSource
L-HydroxyprolineChEBI
(2S)-4-Hydroxypyrrolidine-2-carboxylateGenerator
(4S)-4-Hydroxy-L-prolineHMDB
allo-4-Hydroxy-L-prolineHMDB
allo-4-HydroxyprolineHMDB
allo-Hydroxy-L-prolineHMDB
cis-4-Hydroxy-L-prolineHMDB
cis-4-HydroxyprolineHMDB
L-4-allo-Hydroxy-prolineHMDB
L-4-Hydroxy-prolineHMDB
L-4-HydroxyprolineHMDB
L-AllohydroxyprolineHMDB
Chemical FormulaC5H9NO3
Average Molecular Weight131.1299
Monoisotopic Molecular Weight131.058243159
IUPAC Name(2S)-4-hydroxypyrrolidine-2-carboxylic acid
Traditional Name4 hydroxyproline
CAS Registry Number30724-02-8
SMILES
OC1CN[C@@H](C1)C(O)=O
InChI Identifier
InChI=1S/C5H9NO3/c7-3-1-4(5(8)9)6-2-3/h3-4,6-7H,1-2H2,(H,8,9)/t3?,4-/m0/s1
InChI KeyInChIKey=PMMYEEVYMWASQN-BKLSDQPFSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine carboxylic acid
  • Pyrrolidine
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Secondary aliphatic amine
  • Carboxylic acid
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point274 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility361 mg/mL at 25 °CNot Available
LogP-3.17HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility492.0 mg/mLALOGPS
logP-3.3ALOGPS
logP-3.7ChemAxon
logS0.57ALOGPS
pKa (Strongest Acidic)1.64ChemAxon
pKa (Strongest Basic)10.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area69.56 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity29.38 m3·mol-1ChemAxon
Polarizability12.32 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-3900000000-c0b2003453a19bfc37d7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02t9-9400000000-1e365ce40f4342e10983View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9000000000-95dfbe4457c528ad98edView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-4328dec4e0cf083ba05dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03yi-8900000000-a8cabd8deaa24da3b219View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-9000000000-1216ea21a7fab26c6cf7View in MoNA
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)SMP00362Not Available
Creatine deficiency, guanidinoacetate methyltransferase deficiencySMP00504Not Available
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)SMP00188Not Available
Hyperornithinemia with gyrate atrophy (HOGA)SMP00505Not Available
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]SMP00506Not Available
Hyperprolinemia Type ISMP00361Not Available
Hyperprolinemia Type IISMP00360Not Available
L-arginine:glycine amidinotransferase deficiencySMP00507Not Available
Ornithine Aminotransferase Deficiency (OAT Deficiency)SMP00363Not Available
Prolidase Deficiency (PD)SMP00207Not Available
Prolinemia Type IISMP00208Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot Available
Normal
  • Not Applicable
details
UrineDetected and Quantified0.15 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified5.6 +/- 0.67 uMAdult (>18 years old)BothAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.28 +/- 0.055 uMAdult (>18 years old)BothAlzheimer's disease details
UrineDetected and Quantified0.21 +/- 0.017 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. [17031479 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023823
KNApSAcK IDNot Available
Chemspider ID62461
KEGG Compound IDC01015
BioCyc IDProtein-hydroxyprolines
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB06055
Metagene LinkHMDB06055
METLIN IDNot Available
PubChem Compound69248
PDB IDNot Available
ChEBI ID18240
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Tasanen K, Eble JA, Aumailley M, Schumann H, Baetge J, Tu H, Bruckner P, Bruckner-Tuderman L: Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15. J Biol Chem. 2000 Feb 4;275(5):3093-9. [10652291 ]
  2. Keskiaho K, Hieta R, Sormunen R, Myllyharju J: Chlamydomonas reinhardtii has multiple prolyl 4-hydroxylases, one of which is essential for proper cell wall assembly. Plant Cell. 2007 Jan;19(1):256-69. Epub 2007 Jan 12. [17220203 ]
  3. Lafranconi WM, Duhamel RC, Brendel K, Huxtable RJ: Differentiation of the cardiac and pulmonary toxicity of monocrotaline, a pyrrolizidine alkaloid. Biochem Pharmacol. 1984 Jan 15;33(2):191-7. [6200114 ]
  4. Sodian R, Hoerstrup SP, Sperling JS, Martin DP, Daebritz S, Mayer JE Jr, Vacanti JP: Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves. ASAIO J. 2000 Jan-Feb;46(1):107-10. [10667727 ]
  5. ADAMS E, GOLDSTONE A, SINGH RM, ROSSO G: SUBSTRATE ACTIVITY OF 3-HYDROXYPROLINE ISOMERS FOR ENZYMES ACTIVE WITH 4-HYDROXYPROLINE. Biochim Biophys Acta. 1964 Jul 8;89:164-6. [14212996 ]
  6. Last JA, Reiser KM, Tyler WS, Rucker RB: Long-term consequences of exposure to ozone. I. Lung collagen content. Toxicol Appl Pharmacol. 1984 Jan;72(1):111-8. [6710477 ]
  7. Koike K, Li Y, Seo M, Sakurada I, Tezuka K, Uchikura K: Free 4-hydroxyproline content in serum of bedridden aged people is elevated due to fracture. Biol Pharm Bull. 2000 Jan;23(1):101-3. [10706420 ]
  8. Burjanadze TV: New analysis of the phylogenetic change of collagen thermostability. Biopolymers. 2000 May;53(6):523-8. [10775067 ]
  9. Dixon IM, Hao J, Reid NL, Roth JC: Effect of chronic AT(1) receptor blockade on cardiac Smad overexpression in hereditary cardiomyopathic hamsters. Cardiovasc Res. 2000 May;46(2):286-97. [10773233 ]
  10. Turpeenniemi-Hujanen T, Myllyla R: Concomitant hydroxylation of proline and lysine residues in collagen using purified enzymes in vitro. Biochim Biophys Acta. 1984 Jul 16;800(1):59-65. [6331520 ]

Enzymes

General function:
Involved in D-amino-acid oxidase activity
Specific function:
Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids.
Gene Name:
DAO
Uniprot ID:
P14920
Molecular weight:
39473.75
General function:
Involved in oxidoreductase activity
Specific function:
Housekeeping enzyme that catalyzes the last step in proline biosynthesis. In some cell types, such as erythrocytes, its primary function may be the generation of NADP(+). Can utilize both NAD and NADP. Has higher affinity for NADP, but higher catalytic efficiency with NADH.
Gene Name:
PYCR2
Uniprot ID:
Q96C36
Molecular weight:
25867.975
General function:
Involved in proline dehydrogenase activity
Specific function:
Converts proline to delta-1-pyrroline-5-carboxylate.
Gene Name:
PRODH
Uniprot ID:
O43272
Molecular weight:
56196.675
General function:
Involved in ion channel activity
Specific function:
Cation channel essential for the depolarizing photoresponse of retinal ON bipolar cells. It is part of the GRM6 signaling cascade. May play a role in metastasis suppression. May act as a spontaneously active, calcium-permeable plasma membrane channel
Gene Name:
TRPM1
Uniprot ID:
Q7Z4N2
Molecular weight:
182177.0