L-Proline (T3D4411)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (23)XML
Targets (23)
Record Information
Version2.0
Creation Date2014-08-29 06:51:05 UTC
Update Date2018-03-21 17:46:20 UTC
Accession NumberT3D4411
Identification
Common NameL-Proline
ClassSmall Molecule
DescriptionL-proline is one of the twenty amino acids used in living organisms as the building blocks of proteins. Proline is sometimes called an imino acid, although the IUPAC definition of an imine requires a carbon-nitrogen double bond. Proline is a non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. Proline is derived from the amino acid L-glutamate in which glutamate-5-semialdehyde is first formed by glutamate 5-kinase and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This semialdehyde can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase, or turned into ornithine by ornithine aminotransferase, followed by cyclization by ornithine cyclodeaminase to form proline. L-Proline has been found to act as a weak agonist of the glycine receptor and of both NMDA and non-NMDA ionotropic glutamate receptors. It has been proposed to be a potential endogenous excitotoxin/neurotoxin. Studies in rats have shown that when injected into the brain, proline non-selectively destroys pyramidal and granule cells (PMID: 3409032). Therefore, under certain conditions proline can act as a neurotoxin and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of proline are associated with at least five inborn errors of metabolism, including hyperprolinemia type I, hyperprolinemia type II, iminoglycinuria, prolinemia type II, and pyruvate carboxylase deficiency. People with hyperprolinemia type I often do not show any symptoms even though they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems. Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. Hyperprolinemia type II has signs and symptoms that vary in severity, and is more likely than type I to involve seizures or intellectual disability.
Compound Type
  • Amine
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Non-Essential Amino Acid
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(-)-(S)-Proline
(-)-2-Pyrrolidinecarboxylate
(-)-2-Pyrrolidinecarboxylic acid
(-)-Proline
(2S)-Pyrrolidine-2-carboxylic acid
(S)-(-)-Proline
(S)-(-)-Pyrrolidine-2-carboxylate
(S)-(-)-Pyrrolidine-2-carboxylic acid
(S)-2-Carboxypyrrolidine
(S)-2-Pyrralidinecarboxylate
(S)-2-Pyrralidinecarboxylic acid
(S)-2-Pyrrolidinecarboxylate
(S)-2-Pyrrolidinecarboxylic acid
(S)-Proline
(S)-Pyrrolidine-2-carboxylic acid
(−)-(S)-proline
(−)-2-pyrrolidinecarboxylic acid
(−)-proline
2-Pyrrolidinecarboxylate
2-Pyrrolidinecarboxylic acid
L-(-)-Proline
L-alpha-pyrrolidinecarboxylic acid
L-Prolin
L-pyrrolidine-2-carboxylic acid
L-α-pyrrolidinecarboxylic acid
P
Prolina
Proline
Prolinum
Chemical FormulaC5H9NO2
Average Molecular Mass115.131 g/mol
Monoisotopic Mass115.063 g/mol
CAS Registry Number147-85-3
IUPAC Name(2S)-pyrrolidine-2-carboxylic acid
Traditional NameL-proline
SMILES[H][C@]1(CCCN1)C(O)=O
InChI IdentifierInChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1
InChI KeyInChIKey=ONIBWKKTOPOVIA-BYPYZUCNSA-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
  • Amino acid
  • Carboxylic acid
  • Secondary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Secondary amine
  • Organoheterocyclic compound
  • Azacycle
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Lysosome
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • All Tissues
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020 map00330
Transcription/TranslationSMP00019 Not Available
Hyperprolinemia Type ISMP00361 Not Available
Hyperprolinemia Type IISMP00360 Not Available
IminoglycinuriaSMP00193 Not Available
Prolinemia Type IISMP00208 Not Available
Pyruvate Carboxylase DeficiencySMP00350 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point221 dec°C
Boiling PointNot Available
Solubility1.62E+005 mg/L (at 25°C)
LogP-2.54
Predicted Properties
PropertyValueSource
Water Solubility365 g/LALOGPS
logP-2.7ALOGPS
logP-2.6ChemAxon
logS0.5ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)11.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.33 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity28.06 m³·mol⁻¹ChemAxon
Polarizability11.5 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-0006-0910000000-a9127c0e370afb80259b2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-000f-0910000000-3195f21e625520d513162014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0006-0900000000-119af746c347969e8ae72014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-006x-8900000000-b31beabb1ed6235e71452014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-00di-9100000000-c1c67bc521741ee891cb2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0006-1900000000-84e6fb318323fd0261b12014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-00xs-8910000000-74b0c34ca5fd7c85f1d92014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00fu-9000000000-716c3d01b301162863b62017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-0900000000-0d7354201ed866c87b132017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0006-0910000000-a9127c0e370afb80259b2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000f-0910000000-3195f21e625520d513162017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0006-0900000000-119af746c347969e8ae72017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-QQ (Non-derivatized)splash10-001i-1920000000-09006ee4e7a137d8a45a2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-006x-8900000000-b31beabb1ed6235e71452017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0006-1900000000-84e6fb318323fd0261b12017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00xs-8910000000-74b0c34ca5fd7c85f1d92017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-9100000000-c1c67bc521741ee891cb2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00fu-9000000000-d203e3dfb0701403a75b2016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9000000000-56471980a375d26046ca2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00xr-9600000000-ba51a901e786b1a4663e2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-9000000000-f72e2f3812225708fc562012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00di-9000000000-59887da6580f63bcc1c52012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-00fu-9000000000-c69dcaf7cb2d1e9d285e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-0930000000-984f9a23ebfe28f950172012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-9000000000-f75575cac28a54aa923d2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-00di-9000000000-221cfb8c82f3df76eb512012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-0900000000-e5741fd9870218d57caf2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-0900000000-6bc9b4e775be37fa18d92012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-9000000000-a8eb419b26655a6a1dab2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-00di-9000000000-873ee03b61d1ffcae70f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-014i-0900000000-61d583960651669fb9e62012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-03di-0900000000-2c23774af5f6a0c217d52012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-03di-0900000000-d89c1e626ef24a79c89f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-03di-1900000000-fc27094f2eb75e65b4382012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-014i-1900000000-3221c23504b8847abf8d2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-00di-9100000000-8169367f5127c57fae122012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-9000000000-f704eb8402fcacfccd182012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-00di-9000000000-ccd74eea36efab2cbab82012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00di-9000000000-9f214692cd39a65818132012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - CE-ESI-TOF (CE-system connected to 6210 Time-of-Flight MS, Agilent) , Positivesplash10-014i-0900000000-ef038c77922e4c89eeb02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-00di-9400000000-4073ea1df57a60b36d692012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-00di-9000000000-495fdbd2f565bd7946322012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-03di-0900000000-e1d0a4b20419dc7bae922012-08-31View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-6900000000-eba8ceb2a71d2726acd02016-09-12View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 1H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityGlycogenic, by L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde. It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.
MetabolismHepatic
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesL-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of proline are associated with at least 5 inborn errors of metabolism including: Hyperprolinemia Type I, Hyperprolinemia Type II, Iminoglycinuria, Prolinemia Type II and Pyruvate carboxylase deficiency.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00172
HMDB IDHMDB00162
PubChem Compound ID145742
ChEMBL IDCHEMBL54922
ChemSpider ID128566
KEGG IDC00148
UniProt IDNot Available
OMIM ID
ChEBI ID17203
BioCyc IDPRO
CTD IDNot Available
Stitch IDNot Available
PDB IDPRO
ACToR IDNot Available
Wikipedia LinkL-Proline
References
Synthesis Reference

Richard I. Leavitt, “L-Proline production from algae.” U.S. Patent US4383039, issued October, 1968.

MSDSLink
General References
  1. Deng C, Shang C, Hu Y, Zhang X: Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jul 25;775(1):115-20. [12101068 ]
  2. Azizi M, Junot C, Ezan E, Menard J: Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline. Clin Exp Pharmacol Physiol. 2001 Dec;28(12):1066-9. [11903317 ]
  3. Roesel RA, Blankenship PR, Mobley EB, Coryell ME: Increased excretion of histidyl-L-proline diketopiperazine by infants receiving Pregestimil and Nutramigen formulas. Clin Chem. 1986 May;32(5):865-7. [3698278 ]
  4. Chambers ST, Kunin CM: Osmoprotective activity for Escherichia coli in mammalian renal inner medulla and urine. Correlation of glycine and proline betaines and sorbitol with response to osmotic loads. J Clin Invest. 1987 Nov;80(5):1255-60. [3316273 ]
  5. Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. [12297216 ]
  6. Azizi M, Ezan E, Reny JL, Wdzieczak-Bakala J, Gerineau V, Menard J: Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans. Hypertension. 1999 Mar;33(3):879-86. [10082503 ]
  7. Hart W, van den Hamer CJ, van der Sluys Veer J: The use of hydroxy-DL-proline-2-(14)C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency. Clin Nephrol. 1976 Sep;6(3):379-87. [991465 ]
  8. Kanwar YS, Krakower CA, Manaligod JR, Justice P, Wong PW: Biochemical, morphological and hybrid studies in hyperprolinemic mice. Biomedicine. 1975 May;22(3):209-16. [240452 ]
  9. Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81. [533224 ]
  10. Lu SH, Ohshima H, Fu HM, Tian Y, Li FM, Blettner M, Wahrendorf J, Bartsch H: Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C. Cancer Res. 1986 Mar;46(3):1485-91. [3943105 ]
  11. Hausmann D: [Post-traumatic imbalances of plasma amino acids--interference factors or defense mechanisms? A study of protein metabolism in severe craniocerebral trauma]. Anasth Intensivther Notfallmed. 1988 Feb;23(1):14-21. [3364629 ]
  12. Scriver CR, McInnes RR, Mohyuddin F: Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1431-5. [1055415 ]
  13. Boden G, Rezvani I, Owen OE: Effects of glucagon on plasma amino acids. J Clin Invest. 1984 Mar;73(3):785-93. [6142902 ]
  14. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. [12097436 ]
  15. Feldman JM, Plonk JW, Admiraal J, Sidbury JB: Plasma amino acids in patients with the carcinoid syndrome. Cancer. 1976 Nov;38(5):2127-31. [136295 ]
  16. Humbertclaude V, Rivier F, Roubertie A, Echenne B, Bellet H, Vallat C, Morin D: Is hyperprolinemia type I actually a benign trait? Report of a case with severe neurologic involvement and vigabatrin intolerance. J Child Neurol. 2001 Aug;16(8):622-3. [11510941 ]
  17. 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. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Peptidyl-prolyl cis-trans isomerase A
General Function:
Virion binding
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Gene Name:
PPIA
Uniprot ID:
P62937
Molecular Weight:
18012.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
2. Peptidyl-prolyl cis-trans isomerase B
General Function:
Unfolded protein binding
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Gene Name:
PPIB
Uniprot ID:
P23284
Molecular Weight:
23742.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
3. Proline dehydrogenase 1, mitochondrial
General Function:
Proline dehydrogenase activity
Specific Function:
Converts proline to delta-1-pyrroline-5-carboxylate.
Gene Name:
PRODH
Uniprot ID:
O43272
Molecular Weight:
68001.405 Da
References
  1. Huang TC, Huang YW, Hung HJ, Ho CT, Wu ML: Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2-acetyl-1-pyrroline. J Agric Food Chem. 2007 Jun 27;55(13):5097-102. Epub 2007 May 31. [17536821 ]
  2. White TA, Krishnan N, Becker DF, Tanner JJ: Structure and kinetics of monofunctional proline dehydrogenase from Thermus thermophilus. J Biol Chem. 2007 May 11;282(19):14316-27. Epub 2007 Mar 7. [17344208 ]
  3. White TA, Tanner JJ: Cloning, purification and crystallization of Thermus thermophilus proline dehydrogenase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Aug 1;61(Pt 8):737-9. Epub 2005 Jul 8. [16511143 ]
Target Details
4. Pyrroline-5-carboxylate reductase 1, mitochondrial
General Function:
Pyrroline-5-carboxylate reductase 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 Da
References
  1. Huang TC, Huang YW, Hung HJ, Ho CT, Wu ML: Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2-acetyl-1-pyrroline. J Agric Food Chem. 2007 Jun 27;55(13):5097-102. Epub 2007 May 31. [17536821 ]
  2. Hu CA, Donald SP, Yu J, Lin WW, Liu Z, Steel G, Obie C, Valle D, Phang JM: Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. Mol Cell Biochem. 2007 Jan;295(1-2):85-92. Epub 2006 Jul 28. [16874462 ]
  3. Meng Z, Lou Z, Liu Z, Hui D, Bartlam M, Rao Z: Purification, characterization, and crystallization of human pyrroline-5-carboxylate reductase. Protein Expr Purif. 2006 Sep;49(1):83-7. Epub 2006 Mar 20. [16600630 ]
Target Details
5. Pyrroline-5-carboxylate reductase 2
General Function:
Pyrroline-5-carboxylate reductase 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 (PubMed:2722838, PubMed:6894153). Involved in cellular response to oxidative stress (PubMed:25865492).
Gene Name:
PYCR2
Uniprot ID:
Q96C36
Molecular Weight:
33636.815 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Murahama M, Yoshida T, Hayashi F, Ichino T, Sanada Y, Wada K: Purification and characterization of Delta(1)-pyrroline-5-carboxylate reductase isoenzymes, indicating differential distribution in spinach (Spinacia oleracea L.) leaves. Plant Cell Physiol. 2001 Jul;42(7):742-50. [11479381 ]
Target Details
6. Pyrroline-5-carboxylate reductase 3
General Function:
Pyrroline-5-carboxylate reductase activity
Specific Function:
Not Available
Gene Name:
PYCRL
Uniprot ID:
Q53H96
Molecular Weight:
28663.025 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Target Details
7. Bifunctional glutamate/proline--tRNA ligase
General Function:
Rna stem-loop binding
Specific Function:
Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:
EPRS
Uniprot ID:
P07814
Molecular Weight:
170589.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
8. Peptidyl-prolyl cis-trans isomerase C
General Function:
Peptidyl-prolyl cis-trans isomerase activity
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Gene Name:
PPIC
Uniprot ID:
P45877
Molecular Weight:
22763.165 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
9. Peptidyl-prolyl cis-trans isomerase F, mitochondrial
General Function:
Peptidyl-prolyl cis-trans isomerase activity
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.
Gene Name:
PPIF
Uniprot ID:
P30405
Molecular Weight:
22040.09 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
10. Peptidyl-prolyl cis-trans isomerase G
General Function:
Poly(a) rna binding
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing.
Gene Name:
PPIG
Uniprot ID:
Q13427
Molecular Weight:
88616.535 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
11. Peptidyl-prolyl cis-trans isomerase H
General Function:
Ribonucleoprotein complex binding
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. May act as a chaperone.
Gene Name:
PPIH
Uniprot ID:
O43447
Molecular Weight:
19208.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
12. Probable proline--tRNA ligase, mitochondrial
General Function:
Proline-trna ligase activity
Specific Function:
Not Available
Gene Name:
PARS2
Uniprot ID:
Q7L3T8
Molecular Weight:
53262.18 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
13. Proline synthase co-transcribed bacterial homolog protein
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
PROSC
Uniprot ID:
O94903
Molecular Weight:
30343.7 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
14. Prolyl 3-hydroxylase 1
General Function:
Protein complex binding
Specific Function:
Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.
Gene Name:
P3H1
Uniprot ID:
Q32P28
Molecular Weight:
83393.195 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
15. Prolyl 3-hydroxylase 2
General Function:
Procollagen-proline 3-dioxygenase activity
Specific Function:
Shows prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types II, IV and V.
Gene Name:
P3H2
Uniprot ID:
Q8IVL5
Molecular Weight:
80983.685 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
16. Prolyl 3-hydroxylase 3
General Function:
Procollagen-proline 3-dioxygenase activity
Specific Function:
Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types IV and V.
Gene Name:
P3H3
Uniprot ID:
Q8IVL6
Molecular Weight:
81835.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
17. Prolyl 4-hydroxylase subunit alpha-1
General Function:
Procollagen-proline 4-dioxygenase 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:
61048.775 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
18. Prolyl 4-hydroxylase subunit alpha-2
General Function:
Procollagen-proline 4-dioxygenase 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:
60901.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
19. Pyrroline-5-carboxylate reductase
General Function:
Pyrroline-5-carboxylate reductase activity
Specific Function:
Not Available
Gene Name:
P5CR2
Uniprot ID:
Q4W8W1
Molecular Weight:
33726.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
20. Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner.
Gene Name:
SLC6A14
Uniprot ID:
Q9UN76
Molecular Weight:
72152.145 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
21. Sodium-dependent proline transporter
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A7
Uniprot ID:
Q99884
Molecular Weight:
70909.935 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
22. Trans-3-hydroxy-L-proline dehydratase
General Function:
Trans-l-3-hydroxyproline dehydratase activity
Specific Function:
Catalyzes the dehydration of trans-3-hydroxy-L-proline to Delta(1)-pyrroline-2-carboxylate (Pyr2C). May be required to degrade trans-3-hydroxy-L-proline from the diet and originating from the degradation of proteins such as collagen-IV that contain it.
Gene Name:
L3HYPDH
Uniprot ID:
Q96EM0
Molecular Weight:
38137.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
23. Proton-coupled amino acid transporter 1
General Function:
L-proline transmembrane transporter activity
Specific Function:
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid (By similarity).
Gene Name:
SLC36A1
Uniprot ID:
Q7Z2H8
Molecular Weight:
53075.045 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1600 uMNot AvailableBindingDB 50000100
References
  1. Thondorf I, Voigt V, Schafer S, Gebauer S, Zebisch K, Laug L, Brandsch M: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). Bioorg Med Chem. 2011 Nov 1;19(21):6409-18. doi: 10.1016/j.bmc.2011.08.058. Epub 2011 Sep 5. [21955456 ]