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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-11-09 23:14:23 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?1582752152
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:

Process

Naturally occurring process:

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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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-0950000000-5b1c397e26b28e872d20Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-9530000000-00db00b15ab5341d7d64Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eSpectrum
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-001l-1960000000-abcd0377696d2b52d815Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-0590000000-75e03328fb2d44469057Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9530000000-00db00b15ab5341d7d64Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eSpectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-001l-1960000000-abcd0377696d2b52d815Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-97328204c6b60a244616Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-468aeb79950a9e6dadc6Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0900000000-40c0bfa9451caacaf422Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a6r-9100000000-af92b4a861832ca4ec13Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-02mu-9670000000-81c8390bdfa262fa9b2fSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0019-9700000000-ea3ed008938a57d1263cSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014r-9000000000-0b76109525f362b600a0Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014l-9000000000-477e41e40831316e68acSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0019-9300000000-7228a10f32d447b58ee0Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-11800ca52c6e911f8313Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-001i-0900000000-11800ca52c6e911f8313Spectrum
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-b6bba00a324b6eab209fSpectrum
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-ba9df49a4d967cf8851dSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-000i-9000000000-6d125b0bb59101e9ce53Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0019-9300000000-7228a10f32d447b58ee0Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-5bcced64c9dfeb96876fSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-b575fa8df5e2d8bb3a99Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-3900000000-a10576d40ff1d7fc707aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02t9-9400000000-8b66308781907cdf6304Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9000000000-7f9d42864b2decdbdd1dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-bfc9154f784caa2e61a7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02ar-9800000000-750b3fd4f0e1dcb8ef4cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00r6-9000000000-efe39f47f6ee937ded3dSpectrum
MSMass Spectrum (Electron Ionization)splash10-00ku-9000000000-f5bd67093b2f30a6f62bSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Mitochondria
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Locations
  • Epidermis
  • Fibroblasts
  • Kidney
  • Liver
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Female
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Female
Normal
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>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 but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodDetected and Quantified4.00-30.0 uMAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedNot SpecifiedBoth
Normal
details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedNormal details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected and Quantified10 +/- 10 nmol/g wet fecesAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>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 QuantifiedNot QuantifiedAdult (>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 Quantified497.46 +/- 203.51 umol/mmol creatinineNewborn (0-30 days old)Both
Normal
details
UrineDetected and Quantified720.19 +/- 373.10 umol/mmol creatinineNewborn (0-30 days old)Both
Normal
details
UrineDetected and Quantified723.58 +/- 260.04 umol/mmol creatinineNewborn (0-30 days old)Both
Normal
details
UrineDetected and Quantified<2.49 umol/mmol creatinineAdolescent (13-18 years old)Not SpecifiedNormal details
UrineDetected and Quantified0.26-0.64 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified8.12-92.19 umol/mmol creatinineNewborn (0-30 days old)BothNormal
    • López Hernández Y...
details
UrineDetected and Quantified28.41(16.96-78.82) umol/mmol creatinineNewborn (0-30 days old)FemaleNormal
    • López Hernández Y...
details
UrineDetected and Quantified34.65(8.07-96.55) umol/mmol creatinineNewborn (0-30 days old)MaleNormal
    • López Hernández Y...
details
UrineDetected and Quantified<1.70 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified<3.289 umol/mmol creatinineAdult (>18 years old)BothNormal
      Not Available
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected and Quantified<286.82 umol/mmol creatinineInfant (0-1 year old)Not SpecifiedNormal details
UrineDetected and Quantified1.37 +/- 0.78 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<10.067 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified0.26-0.45 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified186.45 (145.78-227.11) umol/mmol creatinineNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
    • West Cadwell, N.J...
    • Basel, Switzerlan...
details
UrineDetected and Quantified< 2.0 umol/mmol creatinineInfant (6 months - <1 year old)Both
Normal
details
UrineDetected and Quantified<10.0 umol/mmol creatinineInfant (1 - 6 months old)Both
Normal
details
UrineDetected and Quantified7.5 +/- 2.9 umol/mmol creatinineNewborn (0-30 days old)Both
Normal
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 Quantified<5.20 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified4-230 umol/mmol creatinineNewborn (0-30 days 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
UrineDetected and Quantified<2.15 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>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 QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedCrohns disease details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedUlcerative colitis details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedUnclassified IBD details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothColorectal Cancer details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MaleAttachment loss  details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MaleMissing teeth details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MalePeriodontal Probing Depth details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>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
FooDB 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
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000237
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 ]
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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.