Human Metabolome Database: Showing metabocard for 1-Pyrroline-5-carboxylic acid (HMDB0001301)

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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (6) Show 6 proteins XML

enzymes (6) Show 6 proteins

Record Information

Version

4.0

Status

Detected but not Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2020-09-14 22:01:26 UTC

HMDB ID

HMDB0001301

Secondary Accession Numbers

HMDB0002240
HMDB01301
HMDB02240

Metabolite Identification

Common Name

1-Pyrroline-5-carboxylic acid

Description

1-Pyrroline-5-carboxylic acid (CAS: 2906-39-0) 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 into 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

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
1-Pyrroline-5-carboxylate	ChEBI, KEGG
L-1-Pyrroline-5-carboxylate	ChEBI, KEGG
1-Pyrroline-5-carboxylic acid	Generator
(S)-1-Pyrroline-5-carboxylic acid	Generator
L-1-Pyrroline-5-carboxylic acid	Generator
delta-1-Pyrroline-5-carboxylate	MeSH
delta-1-Pyrroline-5-carboxylate, (+-)-isomer	MeSH
delta-1-Pyrroline-5-carboxylic acid	MeSH
delta-1-Pyrroline-5-carboxylate, 14C-labeled, (+-)-isomer	MeSH
delta(1)Pyrroline-5-carboxylate	MeSH
Pyrroline-5-carboxylate	MeSH
(2S)-3,4-Dihydro-2H-pyrrole-2-carboxylic acid	HMDB
(S)-1-Pyrroline-5-carboxylate	HMDB
3,4-Dihydro-2H-pyrrole-2-carboxylic acid	HMDB
delta1-Pyrroline-5-carboxylic acid	HMDB
Δ1-Pyrroline-5-carboxylic acid	HMDB

Chemical Formula

C₅H₇NO₂

Average Molecular Weight

113.1146

Monoisotopic Molecular Weight

113.047678473

IUPAC Name

(2S)-3,4-dihydro-2H-pyrrole-2-carboxylic acid

Traditional Name

L-1-pyrroline-5-carboxylate

CAS Registry Number

64199-88-8

SMILES

OC(=O)[C@@H]1CCC=N1

InChI Identifier

InChI=1S/C5H7NO2/c7-5(8)4-2-1-3-6-4/h3-4H,1-2H2,(H,7,8)/t4-/m0/s1

InChI Key

DWAKNKKXGALPNW-BYPYZUCNSA-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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Alpha 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 Framework

Aliphatic heteromonocyclic compounds

External Descriptors

1-pyrroline-5-carboxylic acid (CHEBI:371 )

Ontology

Disposition

Source:

Endogenous

Biological location:

Organ and components:

Intestine

Subcellular:

Process

Naturally occurring process:

Biological process:

Biochemical pathway:

Role

Indirect biological role:

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	13.1 g/L	ALOGPS
logP	-0.01	ALOGPS
logP	-2.3	ChemAxon
logS	-0.94	ALOGPS
pKa (Strongest Acidic)	1.82	ChemAxon
pKa (Strongest Basic)	6.07	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	49.66 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	27.4 m³·mol⁻¹	ChemAxon
Polarizability	10.72 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03dj-9700000000-f2bc2275638f96dc74ac	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-014i-9100000000-72dff6639c24448bec9c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-014l-9000000000-28eb1358005b28459deb	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-5900000000-0720aa91caee03b9364e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-02t9-9400000000-cfcc87863f675fb12691	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-9000000000-a15b91c200295166bf9e	Spectrum

Biological Properties

Cellular Locations

Mitochondria

Biospecimen Locations

Feces

Tissue Locations

Intestine

Pathways

Name	SMPDB/Pathwhiz	KEGG
Glutamate Metabolism
Arginine and Proline Metabolism
Prolidase Deficiency (PD)		Not Available
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)		Not Available
Hyperprolinemia Type II		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	29808030	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

L-DELTA1-PYRROLINE_5-CARBOXYLATE

BiGG ID

Not Available

Wikipedia Link

1-Pyrroline-5-carboxylic acid

METLIN ID

Not Available

PubChem Compound

440162

PDB ID

Not Available

ChEBI ID

371

Food Biomarker Ontology

Not Available

VMH ID

Not Available

References

Synthesis Reference

Vogel, 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

Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81. [PubMed:533224 ]
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 ]
Wakabayashi Y: Tissue-selective expression of enzymes of arginine synthesis. Curr Opin Clin Nutr Metab Care. 1998 Jul;1(4):335-9. [PubMed:10565370 ]
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 ]
Fleming GA, Hagedorn CH, Granger AS, Phang JM: Pyrroline-5-carboxylate in human plasma. Metabolism. 1984 Aug;33(8):739-42. [PubMed:6748947 ]
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 ]
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)H	details
1-Pyrroline-5-carboxylic acid + NAD + Water → L-Glutamic acid + NADH + Hydrogen Ion	details
1-Pyrroline-5-carboxylic acid + NADP + Water → L-Glutamic acid + NADPH + Hydrogen Ion	details

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)H	details
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Ion	details
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Ion	details

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)H	details
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Ion	details
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Ion	details

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 acceptor	details
L-Proline + Acceptor → 1-Pyrroline-5-carboxylic acid + Reduced acceptor	details

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)H	details
L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Ion	details
L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Ion	details

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 acceptor	details

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

Structure for HMDB0001301 (1-Pyrroline-5-carboxylic acid)

Enzymes

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