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Record Information
Version4.0
Creation Date2007-04-12 21:28:41 UTC
Update Date2017-09-27 08:24:41 UTC
HMDB IDHMDB0006055
Secondary Accession Numbers
  • HMDB06055
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
(2S)-4-Hydroxypyrrolidine-2-carboxylic acidChEBI
cis-4-Hydroxy-L-prolineChEBI
Hydroxy-L-prolineChEBI
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-HydroxyprolineHMDB
L-4-allo-Hydroxy-prolineHMDB
L-4-Hydroxy-prolineHMDB
L-4-HydroxyprolineHMDB
L-AllohydroxyprolineHMDB
4-HydroxyprolineMeSH
OxyprolineMeSH
cis 4 HydroxyprolineMeSH
HydroxyprolineMeSH
4 HydroxyprolineMeSH
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 KeyPMMYEEVYMWASQN-BKLSDQPFSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as proline and derivatives. These 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentProline and derivatives
Alternative Parents
Substituents
  • 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
Ontology
Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Disposition

Biological Location:

  Biofluid and excreta:

Source:

Role

Indirect biological role:

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 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity29.38 m³·mol⁻¹ChemAxon
Polarizability12.32 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
GC-MSGC-MS Spectrum - GC-EI-TOFsplash10-000x-0940000000-a668e3cb89c27d5aaaecView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-9000000000-268874d675b6738960f8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-0900000000-cc0c0c49fda47ff3c20aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-1900000000-091663d1fbe737185a8aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-9100000000-b2aeae336cfe73f5d96eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014r-9000000000-cd33ebf7746baae48364View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-9000000000-f7d527bb54521981a624View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-9000000000-1c34470907bfbc038d07View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-9000000000-2b450c503f28b7e56789View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-9000000000-3885e554a98e35271b27View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-9000000000-59edfed4387af678c85bView in MoNA
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/PathwhizKEGG
Arginine and Proline MetabolismPw000010Pw000010 greyscalePw000010 simpleMap00330
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)Pw000084Pw000084 greyscalePw000084 simpleNot Available
Creatine deficiency, guanidinoacetate methyltransferase deficiencyPw000480Pw000480 greyscalePw000480 simpleNot Available
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)Pw000088Pw000088 greyscalePw000088 simpleNot Available
Hyperornithinemia with gyrate atrophy (HOGA)Pw000481Pw000481 greyscalePw000481 simpleNot Available
Displaying entries 1 - 5 of 12 in total
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    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. [PubMed: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 Link4-hydroxy-L-proline
    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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10706420 ]
    8. Burjanadze TV: New analysis of the phylogenetic change of collagen thermostability. Biopolymers. 2000 May;53(6):523-8. [PubMed: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. [PubMed: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. [PubMed: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