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Showing metabocard for 1-Pyrroline-5-carboxylic acid (HMDB0001301)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (6) Show 6 proteinsXML
enzymes (6) Show 6 proteins
Record Information
Version4.0
StatusDetected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:23:10 UTC
HMDB IDHMDB0001301
Secondary Accession Numbers
  • HMDB0002240
  • HMDB01301
  • HMDB02240
Metabolite Identification
Common Name1-Pyrroline-5-carboxylic acid
Description1-Pyrroline-5-carboxylic acid is an enamine or an imino acid that forms upon the spontaneous dehydration of L-glutamate gamma-semialdehyde in aqueous solutions. The stereoisomer (S)-1-pyrroline-5-carboxylate is an intermediate in glutamate metabolism, arginine degradation, and proline biosynthesis and degradation. It can also be converted into or be formed from three amino acids: L-glutamate, L-ornithine, and L-proline. In particular, it is synthesized via the oxidation of proline by pyrroline-5-carboxylate reductase 1 (PYCR1) (EC 1.5.1.2) or by proline dehydrogenase (PRODH) (EC 1.5.99.8). It is hydrolyzed to L-glutamate by delta-1-pyrroline-5-carboxylate dehydrogenase (ALDH4A1) (EC 1.5.1.12). It is also one of the few metabolites that can act as a precursor to other metabolites of both the urea cycle and the tricarboxylic acid (TCA) cycle. Under certain conditions, pyrroline-5-carboxylate 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 pyrroline-5-carboxylate 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. Hyperprolinemia type II results in high levels of pyrroline-5-carboxylate. People with hyperprolinemia type II have signs and symptoms that vary in severity, but they are more likely than type I to have seizures or intellectual disability. Pyrroline-5-carboxylate is highly reactive and excess quantities have been shown to cause cell death and apoptosis (PMID: 15548746 ).
Structure
Data?1582752190
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
3,4-Dihydro-2H-pyrrole-2-carboxylateChEBI
Delta(1)-Pyrroline-5-carboxylic acidChEBI
3,4-Dihydro-2H-pyrrole-2-carboxylic acidGenerator
delta(1)-Pyrroline-5-carboxylateGenerator
Δ(1)-pyrroline-5-carboxylateGenerator
Δ(1)-pyrroline-5-carboxylic acidGenerator
1-Pyrroline-5-carboxylateGenerator
delta(1)Pyrroline-5-carboxylateHMDB
delta-1-Pyrroline-5-carboxylate, 14C-labeled, (+-)-isomerHMDB
Pyrroline-5-carboxylateHMDB
delta-1-Pyrroline-5-carboxylateHMDB
delta-1-Pyrroline-5-carboxylate, (+-)-isomerHMDB
delta-1-Pyrroline-5-carboxylic acidHMDB
(S)-1-Pyrroline-5-carboxylateHMDB
D1-Pyrroline-5-carboxylateHMDB
D1-Pyrroline-5-carboxylic acidHMDB
DL-1-Pyrroline-5-carboxylateHMDB
DL-1-Pyrroline-5-carboxylic acidHMDB
L-1-Pyrroline-5-carboxylateHMDB
L-delta 1-Pyrroline-5-carboxylateHMDB
Pyrroline 5-carboxylateHMDB
Chemical FormulaC5H7NO2
Average Molecular Weight113.1146
Monoisotopic Molecular Weight113.047678473
IUPAC Name3,4-dihydro-2H-pyrrole-2-carboxylic acid
Traditional Name1-pyrroline-5-carboxylic acid
CAS Registry Number2906-39-0
SMILES
OC(=O)C1CCC=N1
InChI Identifier
InChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8)
InChI KeyDWAKNKKXGALPNW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Pyrroline carboxylic acid
  • Pyrroline carboxylic acid or derivatives
  • Pyrroline
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organoheterocyclic compound
  • Azacycle
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Carbonyl group
  • Imine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility13.1 g/LALOGPS
logP-0.01ALOGPS
logP-2.3ChemAxon
logS-0.94ALOGPS
pKa (Strongest Acidic)1.82ChemAxon
pKa (Strongest Basic)6.07ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.66 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity27.4 m³·mol⁻¹ChemAxon
Polarizability10.7 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00mo-9000000000-8ab2bc6c045679da1664Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-014i-9100000000-34b6b42e5a9e4ff8715fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03dj-9700000000-f2bc2275638f96dc74acSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9100000000-72dff6639c24448bec9cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014l-9000000000-28eb1358005b28459debSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-5900000000-0720aa91caee03b9364eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02t9-9400000000-cfcc87863f675fb12691Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-9000000000-a15b91c200295166bf9eSpectrum
Biological Properties
Cellular Locations
  • Mitochondria
Biospecimen Locations
  • Feces
Tissue Locations
  • Intestine
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
FecesDetected but not Quantified Adult (>18 years old)Both
Normal		 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022542
KNApSAcK IDC00007606
Chemspider ID1159
KEGG Compound IDC04322
BioCyc IDl-delta(1)-pyrroline_5-carboxylate
BiGG ID42766
Wikipedia Link1-Pyrroline-5-carboxylic acid
METLIN ID6145
PubChem Compound1196
PDB IDNot Available
ChEBI ID1372
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceVogel, Henry J.; Davis, Bernard D. Glutamic g-semialdehyde and D1-pyrroline-5-carboxylic acid, intermediates in the biosynthesis of proline. Journal of the American Chemical Society (1952), 74 109-12.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81. [PubMed:533224 ]
  2. Mixson AJ, Phang JM: The uptake of pyrroline 5-carboxylate. Group translocation mediating the transfer of reducing-oxidizing potential. J Biol Chem. 1988 Aug 5;263(22):10720-4. [PubMed:3392037 ]
  3. Wakabayashi Y: Tissue-selective expression of enzymes of arginine synthesis. Curr Opin Clin Nutr Metab Care. 1998 Jul;1(4):335-9. [PubMed:10565370 ]
  4. Onenli-Mungan N, Yuksel B, Elkay M, Topaloglu AK, Baykal T, Ozer G: Type II hyperprolinemia: a case report. Turk J Pediatr. 2004 Apr-Jun;46(2):167-9. [PubMed:15214748 ]
  5. Fleming GA, Hagedorn CH, Granger AS, Phang JM: Pyrroline-5-carboxylate in human plasma. Metabolism. 1984 Aug;33(8):739-42. [PubMed:6748947 ]
  6. 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. [PubMed:11510941 ]
  7. Deuschle K, Funck D, Forlani G, Stransky H, Biehl A, Leister D, van der Graaff E, Kunze R, Frommer WB: The role of [Delta]1-pyrroline-5-carboxylate dehydrogenase in proline degradation. Plant Cell. 2004 Dec;16(12):3413-25. doi: 10.1105/tpc.104.023622. Epub 2004 Nov 17. [PubMed:15548746 ]

Enzymes

Enzyme Details
1. Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
General function:
Involved in oxidoreductase activity
Specific function:
Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.
Gene Name:
ALDH4A1
Uniprot ID:
P30038
Molecular weight:
55117.24
Reactions
1-Pyrroline-5-carboxylic acid + NAD(P)(+) + Water → L-Glutamic acid + NAD(P)Hdetails
1-Pyrroline-5-carboxylic acid + NAD + Water → L-Glutamic acid + NADH + Hydrogen Iondetails
1-Pyrroline-5-carboxylic acid + NADP + Water → L-Glutamic acid + NADPH + Hydrogen Iondetails
Enzyme Details
2. Pyrroline-5-carboxylate reductase 1, mitochondrial
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
L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
Enzyme Details
3. Pyrroline-5-carboxylate reductase 2
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
L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
Enzyme Details
4. Proline dehydrogenase 1, mitochondrial
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
Reactions
L-Proline + acceptor → 1-Pyrroline-5-carboxylic acid + reduced acceptordetails
L-Proline + Acceptor → 1-Pyrroline-5-carboxylic acid + Reduced acceptordetails
Enzyme Details
5. Pyrroline-5-carboxylate reductase 3
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
PYCRL
Uniprot ID:
Q53H96
Molecular weight:
29892.415
Reactions
L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
Enzyme Details
6. Probable proline dehydrogenase 2
General function:
Involved in proline dehydrogenase activity
Specific function:
Converts proline to delta-1-pyrroline-5-carboxylate (Probable).
Gene Name:
PRODH2
Uniprot ID:
Q9UF12
Molecular weight:
58870.115
Reactions
L-Proline + acceptor → 1-Pyrroline-5-carboxylic acid + reduced acceptordetails