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Record Information
Version3.6
Creation Date2006-08-12 20:18:30 UTC
Update Date2016-05-16 17:41:56 UTC
HMDB IDHMDB03411
Secondary Accession NumbersNone
Metabolite Identification
Common NameD-Proline
DescriptionD-proline is an isomer of the naturally occurring amino acid, L-Proline. D-amino acids have been found in relatively high abundance in human plasma and saliva (PMID: 16480744 ). These amino acids may be of bacterial origin, but there is also evidence that they are endogenously produced through amino acid racemase activity. (PMID: 1426150 ).
Structure
Thumb
Synonyms
ValueSource
(R)-2-CarboxypyrrolidineChEBI
(R)-Pyrrolidine-2-carboxylic acidChEBI
D-ProlinChEBI
(2R)-Pyrrolidine-2-carboxylateGenerator
(R)-Pyrrolidine-2-carboxylateGenerator
R)-2-CarboxypyrrolidineHMDB
R-ProlineHMDB
Chemical FormulaC5H9NO2
Average Molecular Weight115.1305
Monoisotopic Molecular Weight115.063328537
IUPAC Name(2R)-pyrrolidine-2-carboxylic acid
Traditional NameD-proline
CAS Registry Number344-25-2
SMILES
OC(=O)[C@H]1CCCN1
InChI Identifier
InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m1/s1
InChI KeyInChIKey=ONIBWKKTOPOVIA-SCSAIBSYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as d-alpha-amino acids. These are alpha amino acids which have the D-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentD-alpha-amino acids
Alternative Parents
Substituents
  • D-alpha-amino acid
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine carboxylic acid
  • Pyrrolidine
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Secondary aliphatic amine
  • Carboxylic acid
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
StatusDetected but not Quantified
Origin
  • Endogenous
  • Microbial
Biofunction
  • Component of Arginine and proline metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
  • Lysosome
  • Peroxisome
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point221 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility365.0 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity28.06 m3·mol-1ChemAxon
Polarizability11.39 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Lysosome
  • Peroxisome
Biofluid Locations
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)SMP00362Not Available
Creatine deficiency, guanidinoacetate methyltransferase deficiencySMP00504Not Available
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)SMP00188Not Available
Hyperornithinemia with gyrate atrophy (HOGA)SMP00505Not Available
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]SMP00506Not Available
Hyperprolinemia Type ISMP00361Not Available
Hyperprolinemia Type IISMP00360Not Available
L-arginine:glycine amidinotransferase deficiencySMP00507Not Available
Ornithine Aminotransferase Deficiency (OAT Deficiency)SMP00363Not Available
Prolidase Deficiency (PD)SMP00207Not Available
Prolinemia Type IISMP00208Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothAutosomal dominant polycystic kidney disease (ADPKD) details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023166
KNApSAcK IDNot Available
Chemspider ID8640
KEGG Compound IDC00763
BioCyc IDD-PROLINE
BiGG ID35916
Wikipedia LinkNot Available
NuGOwiki LinkHMDB03411
Metagene LinkHMDB03411
METLIN IDNot Available
PubChem Compound8988
PDB IDDPR
ChEBI ID16313
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001 Aug;108(3):457-65. [11489939 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Kubilus J, MacDonald MJ, Baden HP: Epidermal proteins of cultured human and bovine keratinocytes. Biochim Biophys Acta. 1979 Jun 19;578(2):484-92. [486533 ]
  6. Meyer W, Poehling HM, Neurand K: Intraepidermal distribution of free amino acids in porcine skin. J Dermatol Sci. 1991 Sep;2(5):383-92. [1742249 ]
  7. Metzner L, Kottra G, Neubert K, Daniel H, Brandsch M: Serotonin, L-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J. 2005 Sep;19(11):1468-73. [16126914 ]
  8. Nagata Y, Higashi M, Ishii Y, Sano H, Tanigawa M, Nagata K, Noguchi K, Urade M: The presence of high concentrations of free D-amino acids in human saliva. Life Sci. 2006 Mar 6;78(15):1677-81. Epub 2006 Feb 9. [16480744 ]
  9. Goan SR, Junghahn I, Wissler M, Becker M, Aumann J, Just U, Martiny-Baron G, Fichtner I, Henschler R: Donor stromal cells from human blood engraft in NOD/SCID mice. Blood. 2000 Dec 1;96(12):3971-8. [11090086 ]
  10. Rhaleb NE, Peng H, Harding P, Tayeh M, LaPointe MC, Carretero OA: Effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in rat cardiac fibroblasts. Hypertension. 2001 Mar;37(3):827-32. [11244003 ]
  11. Watkins NA, Smethurst PA, Allen D, Smith GA, Ouwehand WH: Platelet alphaIIbbeta3 recombinant autoantibodies from the B-cell repertoire of a post-transfusion purpura patient. Br J Haematol. 2002 Mar;116(3):677-85. [11849233 ]
  12. Lalko CC, Deppe E, Ulatowski D, Lutgen A, Hart AP, Patton EA, Lunn DP, Suresh M, Darien BJ: Equine platelet CD62P (P-selectin) expression: a phenotypic and morphologic study. Vet Immunol Immunopathol. 2003 Jan 30;91(2):119-34. [12543548 ]
  13. Ozyurt H, Totan A, Sahin S, Kilinc C, Sogut S, Akyol O: Maternal serum and amniotic fluid hydroxyproline levels in neural tube defects. Fetal Diagn Ther. 2003 Sep-Oct;18(5):321-3. [12913341 ]
  14. Schwan WR, Wetzel KJ, Gomez TS, Stiles MA, Beitlich BD, Grunwald S: Low-proline environments impair growth, proline transport and in vivo survival of Staphylococcus aureus strain-specific putP mutants. Microbiology. 2004 Apr;150(Pt 4):1055-61. [15073314 ]
  15. Bonafe M, Salvioli S, Barbi C, Trapassi C, Tocco F, Storci G, Invidia L, Vannini I, Rossi M, Marzi E, Mishto M, Capri M, Olivieri F, Antonicelli R, Memo M, Uberti D, Nacmias B, Sorbi S, Monti D, Franceschi C: The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death. Cell Death Differ. 2004 Sep;11(9):962-73. [15131588 ]
  16. Sarkar A, Caamano S, Fernandez JM: The elasticity of individual titin PEVK exons measured by single molecule atomic force microscopy. J Biol Chem. 2005 Feb 25;280(8):6261-4. Epub 2005 Jan 4. [15632200 ]
  17. Babraj JA, Cuthbertson DJ, Smith K, Langberg H, Miller B, Krogsgaard MR, Kjaer M, Rennie MJ: Collagen synthesis in human musculoskeletal tissues and skin. Am J Physiol Endocrinol Metab. 2005 Nov;289(5):E864-9. Epub 2005 Jun 21. [15972270 ]
  18. Vitari AC, Deak M, Morrice NA, Alessi DR: The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Biochem J. 2005 Oct 1;391(Pt 1):17-24. [16083423 ]
  19. Broer S: The SLC6 orphans are forming a family of amino acid transporters. Neurochem Int. 2006 May-Jun;48(6-7):559-67. Epub 2006 Mar 15. [16540203 ]
  20. Corfield AP, Clamp JR, Casey AD, Paraskeva C: Characterization of a sialic-acid-rich mucus glycoprotein secreted by a premalignant human colorectal adenoma cell line. Int J Cancer. 1990 Dec 15;46(6):1059-65. [2249893 ]
  21. Wolf GC, Hilton CW, Prasad C, Miller JM Jr, Thorneycroft IH: The neuropeptide histidyl proline diketopiperazine throughout human pregnancy: an inverse correlation with amniotic fluid prolactin. Am J Obstet Gynecol. 1990 Mar;162(3):740-5. [2316580 ]
  22. Prasad C: Cyclo(His-Pro): its distribution, origin and function in the human. Neurosci Biobehav Rev. 1988 Spring;12(1):19-22. [3287238 ]
  23. Linkosalo E, Markkanen H, Syrjanen S: Effects of a lacto-ovo-vegetarian diet on the free amino acid composition of wax-stimulated whole human saliva. J Nutr. 1985 May;115(5):588-92. [3998860 ]
  24. Manicourt D, Brauman H, Orloff S: Synovial fluid beta 2 microglobulin and hydroxyproline fractions in rheumatoid arthritis and nonautoimmune arthropathies. Ann Rheum Dis. 1980 Jun;39(3):207-16. [6158297 ]
  25. Miller DR, Mankin HJ, Shoji H, D'Ambrosia RD: Identification of fibronectin in preparations of osteoarthritic human cartilage. Connect Tissue Res. 1984;12(3-4):267-75. [6478826 ]
  26. Bogovski PA, Rooma MA, Kann JM: Studies on the excretion of endogenously formed N-nitrosoproline. I. Percutaneous excretion of N-nitrosoproline in humans. IARC Sci Publ. 1984;(57):199-204. [6533008 ]
  27. Maurer G, Schreier E, Delaborde S, Nufer R, Shukla AP: Fate and disposition of bromocriptine in animals and man. II: Absorption, elimination and metabolism. Eur J Drug Metab Pharmacokinet. 1983;8(1):51-62. [6861794 ]
  28. Levison PR, Tomalin G: The kinetics of hydrolysis of some extended N-aminoacyl-L-arginine methyl esters by human plasma kallikrein. Evidence for subsites S2 and S3. Biochem J. 1982 Apr 1;203(1):149-53. [6921035 ]
  29. Canalis E, Raisz LG: Effect of fibroblast growth factor on cultured fetal rat calvaria. Metabolism. 1980 Feb;29(2):108-14. [6986532 ]
  30. Whiteley J, Francis MJ, Walton RJ, Smith R: Serum proline imino-peptidase activity in normal adult subjects and in patients with Paget's disease of bone. Clin Chim Acta. 1976 Sep 6;71(2):157-63. [822968 ]
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  32. Nagata Y, Masui R, Akino T: The presence of free D-serine, D-alanine and D-proline in human plasma. Experientia. 1992 Oct 15;48(10):986-8. [1426150 ]

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
Reactions
D-Proline + Oxygen → 1-Pyrroline-2-carboxylic acid + Hydrogen peroxidedetails
General function:
Involved in proline racemase 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