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Hydroxyproline (M2MDB000179)

Record Information
Version2.0
Creation Date2012-05-31 13:00:48 -0600
Update Date2015-09-13 12:56:09 -0600
Secondary Accession Numbers
  • ECMDB00725
Identification
Name:Hydroxyproline
DescriptionHydroxyproline is a common proteinogenic amino acid. Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the C (gamma) atom. Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the C (gamma) atom. It is produced by hydroxylation of the amino acid proline. It is not directly coded for by DNA, however, and is hydroxylated after protein synthesis. (Wikipedia)
Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms:
  • (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylate
  • (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid
  • (2S,4R)-4-hydroxypyrrolidine-2-carboxylate
  • (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
  • (4R)-4-hydroxy-L-proline
  • 4-Hydroxy-2-pyrrolidinecarboxylate
  • 4-Hydroxy-2-pyrrolidinecarboxylic acid
  • 4-Hydroxy-L-proline
  • 4-Hydroxyproline
  • 4-L-Hydroxyproline
  • Delta-Hydroxyproline
  • Hydroxiproline
  • Hydroxy-L-proline
  • Hydroxy-proline
  • Hydroxyproline
  • L-4-Hydroxyproline
  • L-Hydroxyproline
  • L-Threo-4-hydroxyproline
  • LS-hydroxyproline
  • Oxaceprol
  • Trans-4-Hydroxy-L-proline
  • Trans-4-Hydroxyproline
  • Trans-hydroxyproline
  • Trans-L-hydroxyproline
  • δ-Hydroxyproline
Chemical Formula:C5H9NO3
Weight:Average: 131.1299
Monoisotopic: 131.058243159
InChI Key:PMMYEEVYMWASQN-DMTCNVIQSA-N
InChI: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
CAS number:51-35-4
IUPAC Name:(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid
Traditional IUPAC Name:hypro
SMILES:O[C@H]1CN[C@@H](C1)C(O)=O
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
Physical Properties
State:Solid
Charge:0
Melting point:274-275 °C
Experimental Properties:
PropertyValueSource
Water Solubility:361 mg/mL at 25 oC [MERCK INDEX (1996)]PhysProp
LogP:-3.17 [HANSCH,C ET AL. (1995)]PhysProp
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
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
Hydroxyproline + NAD <> Pyrroline hydroxycarboxylic acid + NADH + Hydrogen ion
Hydroxyproline + NADP <> Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen ion
SMPDB Pathways:Not Available
KEGG Pathways:
  • Arginine and proline metabolism ec00330
EcoCyc Pathways:Not Available
Concentrations
ConcentrationStrainMediaGrowth StatusGrowth SystemTemperatureDetails
0.31± 0.04 uMBL21 DE3Luria-Bertani (LB) mediaStationary phase cultures (overnight culture)Shake flask37 oCExperimentally Determined
Download Details
Find out more about how we convert literature concentrations.
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000x-0950000000-5b1c397e26b28e872d20View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00di-9530000000-00db00b15ab5341d7d64View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-001l-1960000000-abcd0377696d2b52d815View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-0590000000-75e03328fb2d44469057View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0950000000-c46b5bba0f41001e3c18View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-9530000000-00db00b15ab5341d7d64View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a4i-1900000000-c0a869abe2f1e9f8c08eView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-001l-1960000000-abcd0377696d2b52d815View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-97328204c6b60a244616View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000x-0940000000-468aeb79950a9e6dadc6View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0900000000-40c0bfa9451caacaf422View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a6r-9100000000-af92b4a861832ca4ec13View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-02mu-9670000000-81c8390bdfa262fa9b2fView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0019-9700000000-ea3ed008938a57d1263cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014r-9000000000-0b76109525f362b600a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014l-9000000000-477e41e40831316e68acView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0019-9300000000-7228a10f32d447b58ee0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-11800ca52c6e911f8313View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-001i-0900000000-11800ca52c6e911f8313View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-b6bba00a324b6eab209fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-001i-1900000000-ba9df49a4d967cf8851dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-000i-9000000000-6d125b0bb59101e9ce53View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0019-9300000000-7228a10f32d447b58ee0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-5bcced64c9dfeb96876fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-9600000000-b575fa8df5e2d8bb3a99View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-014l-9000000000-c036fd15ccf6ed0c554eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-00kr-9000000000-8746de5249187bab94dcView in MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-014i-9000000000-3f70e8e1eef8568e87efView in MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-000i-9200000000-cd32fa744ef013f5ca48View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-000i-9200000000-3ea6a86203c48888d528View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-02tc-9000000000-95aa07d1970d7f83f347View in MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-014r-9000000000-95b2178b5433b4b2db50View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-3900000000-a10576d40ff1d7fc707aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02t9-9400000000-8b66308781907cdf6304View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9000000000-7f9d42864b2decdbdd1dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-bfc9154f784caa2e61a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02ar-9800000000-750b3fd4f0e1dcb8ef4cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00r6-9000000000-efe39f47f6ee937ded3dView in MoNA
MSMass Spectrum (Electron Ionization)splash10-00ku-9000000000-f5bd67093b2f30a6f62bView in MoNA
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
References
References:
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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. Pubmed: 19212411
Synthesis Reference:Adams, 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)
External Links:
ResourceLink
CHEBI ID18095
HMDB IDHMDB00725
Pubchem Compound ID5810
Kegg IDC01157
ChemSpider ID5605
WikipediaHydroxyproline
BioCyc IDL-4-HYDROXY-PROLINE
EcoCyc IDL-4-HYDROXY-PROLINE
Ligand ExpoHYP

Enzymes

Protein Details
1. Pyrroline-5-carboxylate reductase
General function:
Involved in oxidation-reduction process
Specific function:
L-proline + NAD(P)(+) = 1-pyrroline-5- carboxylate + NAD(P)H
Gene Name:
proC
Uniprot ID:
P0A9L8
Molecular weight:
28145
Reactions
L-proline + NAD(P)(+) = 1-pyrroline-5-carboxylate + NAD(P)H.