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
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2019-07-29 19:20:32 UTC
HMDB IDHMDB0000725
Secondary Accession Numbers
  • HMDB0006055
  • HMDB0036576
  • HMDB00725
  • HMDB06055
  • HMDB36576
Metabolite 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, non-essential amino acid. Hydroxyproline and proline play key roles in 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.
Structure
Data?1563860665
Synonyms
ValueSource
(2S,4R)-4-Hydroxy-2-pyrrolidinecarboxylic acidChEBI
(2S,4R)-trans-4-HydroxyprolineChEBI
delta-HydroxyprolineChEBI
Hydroxy-L-prolineChEBI
HydroxyprolineChEBI
HypChEBI
HyproChEBI
L-4-HydroxyprolineChEBI
L-Threo-4-hydroxyprolineChEBI
trans-HydroxyprolineChEBI
trans-L-HydroxyprolineChEBI
L-HydroxyprolineKegg
trans-4-Hydroxy-L-prolineKegg
(2S,4R)-4-Hydroxy-2-pyrrolidinecarboxylateGenerator
Δ-hydroxyprolineGenerator
(2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acidHMDB
(4R)-4-Hydroxy-L-prolineHMDB
4-Hydroxy-2-pyrrolidinecarboxylic acidHMDB
4-Hydroxy-L-prolineHMDB
4-L-HydroxyprolineHMDB
HydroxiprolineHMDB
Hydroxy-prolineHMDB
LS-HydroxyprolineHMDB
OxaceprolHMDB
trans-4-HydroxyprolineHMDB
4 HydroxyprolineHMDB
OxyprolineHMDB
(-)-4-Hydroxy-2-pyrrolidinecarboxylic acidHMDB
(2S,4R)-(-)-4-HydroxyprolineHMDB
(2S,4R)-4-HydroxyprolineHMDB
(R)-4-Hydroxy-(S)-prolineHMDB
(R)-4-Hydroxy-L-prolineHMDB
(S)-HydroxyprolineHMDB
4(R)-Hydroxy-2(S)-pyrrolidinecarboxylic acidHMDB
4(R)-HydroxyprolineHMDB
4-Hydroxy-(S)-prolineHMDB
4-trans-Hydroxy-L-prolineHMDB
L-HyproHMDB
L-trans-4-HydroxyprolineHMDB
NSC 46704HMDB
trans-L-4-HydroxyprolineHMDB
4-HydroxyprolineHMDB
Chemical FormulaC5H9NO3
Average Molecular Weight131.1299
Monoisotopic Molecular Weight131.058243159
IUPAC Name(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
Traditional Namehypro
CAS Registry Number51-35-4
SMILES
O[C@H]1CN[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+/m1/s1
InChI KeyPMMYEEVYMWASQN-DMTCNVIQSA-N
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
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
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point274 - 275 °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
Polarizability12.29 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000x-0950000000-5b1c397e26b28e872d20JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-9530000000-00db00b15ab5341d7d64JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-001l-1960000000-abcd0377696d2b52d815JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-0590000000-75e03328fb2d44469057JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9530000000-00db00b15ab5341d7d64JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-001l-1960000000-abcd0377696d2b52d815JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-97328204c6b60a244616JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-468aeb79950a9e6dadc6JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0900000000-40c0bfa9451caacaf422JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a6r-9100000000-af92b4a861832ca4ec13JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-02mu-9670000000-81c8390bdfa262fa9b2fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0019-9700000000-ea3ed008938a57d1263cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014r-9000000000-0b76109525f362b600a0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014l-9000000000-477e41e40831316e68acJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0019-9300000000-7228a10f32d447b58ee0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-11800ca52c6e911f8313JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-001i-0900000000-11800ca52c6e911f8313JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-b6bba00a324b6eab209fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-ba9df49a4d967cf8851dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-000i-9000000000-6d125b0bb59101e9ce53JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0019-9300000000-7228a10f32d447b58ee0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-5bcced64c9dfeb96876fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-b575fa8df5e2d8bb3a99JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-3900000000-a10576d40ff1d7fc707aJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02t9-9400000000-8b66308781907cdf6304JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9000000000-7f9d42864b2decdbdd1dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-bfc9154f784caa2e61a7JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02ar-9800000000-750b3fd4f0e1dcb8ef4cJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00r6-9000000000-efe39f47f6ee937ded3dJSpectraViewer | MoNA
MSMass Spectrum (Electron Ionization)splash10-00ku-9000000000-f5bd67093b2f30a6f62bJSpectraViewer | MoNA
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular Locations
  • Mitochondria
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Locations
  • Fibroblasts
  • Gingiva
  • Kidney
  • Liver
  • Muscle
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Skin
  • Spleen
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not Quantified Adult (>18 years old)Female
Normal
details
BloodDetected but not Quantified Adult (>18 years old)Female
Normal
details
BloodDetected but not Quantified Adult (>18 years old)Female
Normal
details
BloodDetected and Quantified<91000 uMInfant (0-1 year old)FemaleNormal details
BloodDetected and Quantified16 - 53 uMInfant (0-1 year old)MaleNormal details
BloodDetected and Quantified11.8 (9.9-13.7) uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified40.0 (28.0-55.0) uMNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified40.0 +/- 40.0 uMNewborn (0-30 days old)Not Specified
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified24.0 +/- 13.0 uMChildren (1-13 years old)Male
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified20.0 +/- 12.0 uMChildren (1-13 years old)Female
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified20 +/- 12 uMChildren (1 - 13 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified20.0 +/- 11.0 uMAdult (>18 years old)Male
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified16.0 +/- 9.0 uMAdult (>18 years old)Female
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified24 +/- 13 uMChildren (1 - 13 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified13.0 (3.0-23.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified4.00-30.0 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.0-0.1 uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Not SpecifiedBoth
Normal
details
FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected and Quantified10 +/- 10 nmol/g wet fecesAdult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
SalivaDetected and Quantified0.873 +/- 0.537 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not Quantified Adult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified1.5 +/- 2.6 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified1.1 +/- 2.0 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified0.93 +/- 0.91 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
SalivaDetected and Quantified<0.25 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified0.432 +/- 0.431 uMAdult (>18 years old)Male
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified<0.25 uMAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified0.15 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.26-0.64 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified<3.289 umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified1.37 +/- 0.78 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.26-0.45 umol/mmol creatinineAdult (>18 years old)MaleNormal details
    UrineDetected and Quantified2.0 (2.15-3.36) umol/mmol creatinineNewborn (0-30 days old)BothNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified2 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified6.5 (2.4-12.5) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified88.17 +/- 49.59 umol/mmol creatinineInfant (0-1 year old)BothNormal details
    UrineDetected and Quantified0 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0 umol/mmol creatinineInfant (0-1 year old)Both
    Normal
    details
    UrineDetected and Quantified0 umol/mmol creatinineInfant (0-1 year old)Both
    Normal
    details
    UrineDetected and Quantified<143 umol/mmol creatinineInfant (0-1 year old)FemaleNormal details
    UrineDetected and Quantified0 - 143 umol/mmol creatinineInfant (0-1 year old)MaleNormal details
    Abnormal Concentrations
    BiospecimenStatusValueAgeSexConditionReferenceDetails
    BloodDetected but not Quantified Adult (>18 years old)BothColorectal cancer details
    BloodDetected and Quantified5.66 +/- 0.67 uMElderly (>65 years old)BothAlzheimer's disease details
    BloodDetected and Quantified43.8 +/- 12.5 uMAdult (>18 years old)Both
    Hemodialysis
    details
    BloodDetected and Quantified27.0 +/- 14.1 uMAdult (>18 years old)Both
    Hemodialysis
    details
    BloodDetected and Quantified339 uMInfant (0-1 year old)MaleHydroxyprolinemia details
    BloodDetected and Quantified412000 uMInfant (0-1 year old)FemaleHydroxyprolinemia details
    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
    FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedCrohns disease details
    FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUlcerative colitis details
    FecesDetected but not Quantified Children (6 - 18 years old)Not SpecifiedUnclassified IBD details
    FecesDetected but not Quantified Adult (>18 years old)BothColorectal Cancer details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Colorectal cancer
    details
    SalivaDetected but not Quantified Adult (>18 years old)MaleAttachment loss  details
    SalivaDetected but not Quantified Adult (>18 years old)MaleMissing teeth details
    SalivaDetected but not Quantified Adult (>18 years old)MalePeriodontal Probing Depth details
    SalivaDetected but not Quantified Adult (>18 years old)MaleTooth Decay details
    UrineDetected and Quantified30.862 +/- 12.249 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Eosinophilic esophagitis
      • Mordechai, Hien, ...
    details
    UrineDetected and Quantified0.21 +/- 0.017 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
    UrineDetected and Quantified75 (50-100) umol/mmol creatinineChildren (1-13 years old)BothIminoglycinuria
      • MetaGene: Metabol...
    details
    UrineDetected and Quantified0 umol/mmol creatinineAdolescent (13-18 years old)BothHyperglycinuria details
    UrineDetected and Quantified0 umol/mmol creatinineAdult (>18 years old)BothHyperglycinuria details
    UrineDetected and Quantified1957 umol/mmol creatinineInfant (0-1 year old)FemaleHydroxyprolinemia details
    UrineDetected and Quantified2960 umol/mmol creatinineInfant (0-1 year old)MaleHydroxyprolinemia details
    UrineDetected and Quantified0-250 umol/mmol creatinineChildren (1-13 years old)BothIminoglycinuria details
    UrineDetected and Quantified40-150 umol/mmol creatinineAdult (>18 years old)Female
    Iminoglycinuria
    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 ]
    Hemodialysis
    1. Raj DS, Ouwendyk M, Francoeur R, Pierratos A: Plasma amino acid profile on nocturnal hemodialysis. Blood Purif. 2000;18(2):97-102. [PubMed:10838467 ]
    Colorectal cancer
    1. Ni Y, Xie G, Jia W: Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014 Sep 5;13(9):3857-70. doi: 10.1021/pr500443c. Epub 2014 Aug 14. [PubMed:25105552 ]
    2. Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
    3. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
    Hydroxyprolinemia
    1. la Marca G, Malvagia S, Pasquini E, Donati MA, Gasperini S, Procopio E, Zammarchi E: Hyperhydroxyprolinaemia: a new case diagnosed during neonatal screening with tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19(6):863-4. [PubMed:15723447 ]
    2. Baykal T, Karaaslan I, Gokcay G, Demir F, Laleli Y, Demirkol M: Hyperhydroxyprolinaemia detected in newborn screening with tandem mass spectrometry. J Inherit Metab Dis. 2004;27(6):781-2. [PubMed:15617190 ]
    Crohn's disease
    1. Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
    Ulcerative colitis
    1. Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
    Attachment loss
    1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
    Missing teeth
    1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
    Periodontal Probing Depth
    1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
    Tooth Decay
    1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
    Iminoglycinuria
    1. Broer S, Bailey CG, Kowalczuk S, Ng C, Vanslambrouck JM, Rodgers H, Auray-Blais C, Cavanaugh JA, Broer A, Rasko JE: Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. J Clin Invest. 2008 Dec;118(12):3881-92. doi: 10.1172/JCI36625. Epub 2008 Nov 6. [PubMed:19033659 ]
    2. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
    Eosinophilic esophagitis
    1. (). Mordechai, Hien, and David S. Wishart. .
    Associated OMIM IDs
    DrugBank IDDB08847
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB013511
    KNApSAcK IDC00001370
    Chemspider ID5605
    KEGG Compound IDC01157
    BioCyc ID4-HYDROXY-L-PROLINE
    BiGG ID36935
    Wikipedia LinkHydroxyproline
    METLIN ID257
    PubChem Compound5810
    PDB IDNot Available
    ChEBI ID18095
    References
    Synthesis ReferenceAdams, Elijah; Goldstone, Alfred. Hydroxyproline metabolism. II. Enzymic preparation and properties of D1-pyrroline-3-hydroxy-5-carboxylic acid. Journal of Biological Chemistry (1960), 235 3492-8.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Matsuda Y, Matsumoto K, Yamada A, Ichida T, Asakura H, Komoriya Y, Nishiyama E, Nakamura T: Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology. 1997 Jul;26(1):81-9. [PubMed:9214455 ]
    2. Seibel MJ, Woitge HW: Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitom. 1999 Fall;2(3):299-321. [PubMed:10548826 ]
    3. Kelleher PC: Urinary excretion of hydroxyproline, hydroxylysine and hydroxylysine glycosides by patients with Paget's disease of bone and carcinoma with metastases in bone. Clin Chim Acta. 1979 Mar 15;92(3):373-9. [PubMed:436278 ]
    4. Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. [PubMed:12297216 ]
    5. Akalin FA, Sengun D, Eratalay K, Renda N, Caglayan G: Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in patients with juvenile, rapidly progressive, and adult periodontitis. J Periodontol. 1993 May;64(5):323-9. [PubMed:8515361 ]
    6. Akalin FA, Sengun D, Renda N, Eratalay K, Caglayan G: Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in periodontally healthy human subjects. J Nihon Univ Sch Dent. 1992 Sep;34(3):172-7. [PubMed:1287145 ]
    7. Lee HS, Shun CT, Chiou LL, Chen CH, Huang GT, Sheu JC: Hydroxyproline content of needle biopsies as an objective measure of liver fibrosis: Emphasis on sampling variability. J Gastroenterol Hepatol. 2005 Jul;20(7):1109-14. [PubMed:15955222 ]
    8. Akalin FA, Bozkurt FY, Sengun D, Renda N, Kalfa Z, Eratalay K, Velidedeoglu E: Hydroxyproline and total protein levels in gingiva from patients treated with phenytoin and cyclosporine-A. J Nihon Univ Sch Dent. 1996 Mar;38(1):21-30. [PubMed:8648408 ]
    9. Diaz S, Reyes MV, Zepeda A, Gonzalez GB, Lopez JM, Campino C, Croxatto HB: Norplant((R)) implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod. 1999 Oct;14(10):2499-505. [PubMed:10527977 ]
    10. Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Morelli A, Pruzanski M, Pellicciari R: Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. J Pharmacol Exp Ther. 2005 Oct;315(1):58-68. Epub 2005 Jun 24. [PubMed:15980055 ]
    11. Kondo A, Ishikawa O, Okada K, Miyachi Y, Abe S, Kuboki Y: Measurement of histidinohydroxylysinonorleucine and hydroxyproline in skin collagen by reversed-phase high-performance liquid chromatography after 9-fluorenylmethyl chloroformate labeling. Anal Biochem. 1997 Oct 15;252(2):255-9. [PubMed:9344411 ]
    12. Gerling B, Becker M, Waldschmidt J, Rehmann M, Schuppan D: Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis. J Hepatol. 1996 Jul;25(1):79-84. [PubMed:8836905 ]
    13. Bienkowski RS: A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues. Arch Biochem Biophys. 1984 Mar;229(2):455-8. [PubMed:6703705 ]
    14. Bellon G, Berg R, Chastang F, Malgras A, Borel JP: Separation and evaluation of the cis and trans isomers of hydroxyprolines: effect of hydrolysis on the epimerization. Anal Biochem. 1984 Feb;137(1):151-5. [PubMed:6731795 ]
    15. 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 ]
    16. Shibasaki T, Mori H, Ozaki A: Enzymatic production of trans-4-hydroxy-L-proline by regio- and stereospecific hydroxylation of L-proline. Biosci Biotechnol Biochem. 2000 Apr;64(4):746-50. [PubMed:10830487 ]
    17. Pickersgill IF, Rapoport H: Preparation of functionalized, conformationally constrained DTPA analogues from L- or D-serine and trans-4-hydroxy-L-proline. Hydroxymethyl substituents on the central acetic acid and on the backbone. J Org Chem. 2000 Jun 30;65(13):4048-57. [PubMed:10866623 ]
    18. Song IK, Kang YK: Conformational preference and cis-trans isomerization of 4(R)-substituted proline residues. J Phys Chem B. 2006 Feb 2;110(4):1915-27. [PubMed:16471763 ]
    19. Baldwin JE, Pritchard GJ, Williamson DS: The synthesis of 4-arylsulfanyl-substituted kainoid analogues from trans-4-hydroxy-L-proline. Bioorg Med Chem Lett. 2000 Sep 4;10(17):1927-9. [PubMed:10987419 ]
    20. Miskolzie M, Gera L, Stewart JM, Kotovych G: The importance of the N-terminal beta-turn in bradykinin antagonists. J Biomol Struct Dyn. 2000 Oct;18(2):249-60. [PubMed:11089646 ]
    21. Kofoed J, Darbre T, Reymond JL: Dual mechanism of zinc-proline catalyzed aldol reactions in water. Chem Commun (Camb). 2006 Apr 14;(14):1482-4. Epub 2006 Mar 2. [PubMed:16575434 ]
    22. Kuttan R, Radhakrishnan AN: Studies on bound trans-4-hydroxy-L-proline in sandal (Santalum album L.). Biochem J. 1970 Oct;119(4):651-7. [PubMed:5493503 ]
    23. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
    24. 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 ]
    25. 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 ]
    26. 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 ]
    27. 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 ]
    28. 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 ]
    29. 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 ]
    30. Burjanadze TV: New analysis of the phylogenetic change of collagen thermostability. Biopolymers. 2000 May;53(6):523-8. [PubMed:10775067 ]
    31. 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 ]
    32. 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 ]
    33. 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 ]
    34. Nogueira Ade C, Vale RG, Gomes AL, Dantas EH: The effect of muscle actions on the level of connective tissue damage. Res Sports Med. 2011 Oct;19(4):259-70. doi: 10.1080/15438627.2011.608046. [PubMed:21988268 ]
    35. Lee KW, Kim SJ, Park JB, Lee KJ: Relationship between depression anxiety stress scale (DASS) and urinary hydroxyproline and proline concentrations in hospital workers. J Prev Med Public Health. 2011 Jan;44(1):9-13. doi: 10.3961/jpmph.2011.44.1.9. [PubMed:21483218 ]
    36. (). Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.. .

    Only showing the first 10 proteins. There are 15 proteins in total.

    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:
    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
    Gene Name:
    P4HA2
    Uniprot ID:
    O15460
    Molecular weight:
    60632.19
    Reactions
    L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.
    Gene Name:
    PYCR1
    Uniprot ID:
    P32322
    Molecular weight:
    33360.27
    Reactions
    4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Iondetails
    4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Iondetails
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
    Gene Name:
    P4HA1
    Uniprot ID:
    P13674
    Molecular weight:
    60966.645
    Reactions
    L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
    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
    Reactions
    4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Iondetails
    4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Iondetails
    General function:
    Involved in serine-type endopeptidase activity
    Specific function:
    Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF- kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline
    Gene Name:
    DPP4
    Uniprot ID:
    P27487
    Molecular weight:
    88277.9
    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 oxidoreductase activity
    Specific function:
    Not Available
    Gene Name:
    PYCRL
    Uniprot ID:
    Q53H96
    Molecular weight:
    29892.415
    Reactions
    4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Iondetails
    4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Iondetails
    General function:
    Involved in sodium:dicarboxylate symporter activity
    Specific function:
    Transporter for alanine, serine, cysteine, and threonine. Exhibits sodium dependence
    Gene Name:
    SLC1A4
    Uniprot ID:
    P43007
    Molecular weight:
    55722.5
    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

    Only showing the first 10 proteins. There are 15 proteins in total.