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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (15) Show 15 proteins XML

Record Information

Version

5.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2023-05-30 20:56:02 UTC

HMDB ID

HMDB0000725

Secondary Accession Numbers

HMDB0006055
HMDB0036576
HMDB00725
HMDB06055
HMDB36576

Metabolite Identification

Common Name

4-Hydroxyproline

Description

4-Hydroxyproline (hydroxyproline or Hyp) is a major component of the protein collagen. Hydroxyproline is produced by hydroxylation of the amino acid proline and is, therefore, a post-translationally modified, non-essential amino acid. Hydroxyproline and proline play key roles in collagen stability. In particular, they permit the sharp twisting of the collagen helix. Hydroxyproline is found in few proteins other than collagen. The only other mammalian protein which includes hydroxyproline is elastin. For this reason, hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount in tissue or biological samples. Increased serum and urine levels of hydroxyproline have been found in Paget's disease (PMID: 436278 ). Hydroxyproline (Hyp) content in biological fluids is used as a parameter of collagen catabolism, especially bone resorption or tissue degradation. Bedridden and elderly individuals show significantly elevated serum levels of hydroxyproline in comparison to normal, active individuals (PMID: 10706420 ). Elevated levels of urinary hydroxyproline are also indicative of muscle damage (PMID: 21988268 ). Increased reactive oxygen species (ROS) are also known to accelerate collagen degradation. Hydroxyproline levels increase in cases of depression and stress (PMID: 21483218 ). 4-Hydroxyproline is found to be associated with Alzheimer's disease, and also hydroxyprolinemia and iminoglycinuria which are both inborn errors of metabolism. 4-Hydroxyproline is also involved in metabolic disorders such as hyperprolinemia type I, hyperornithinemia with gyrate atrophy (HOGA), L-arginine:glycine amidinotransferase deficiency, creatine deficiency, and guanidinoacetate methyltransferase deficiency. A deficiency in ascorbic acid can result in impaired hydroxyproline formation (PubChem). trans-4-Hydroxy-L-proline is a biomarker for the consumption of processed meat.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

View in JSmol View Stereo Labels

Synonyms

Value	Source
(2S,4R)-4-Hydroxy-2-pyrrolidinecarboxylic acid	ChEBI
(2S,4R)-trans-4-Hydroxyproline	ChEBI
delta-Hydroxyproline	ChEBI
Hydroxy-L-proline	ChEBI
Hydroxyproline	ChEBI
Hyp	ChEBI
Hypro	ChEBI
L-4-Hydroxyproline	ChEBI
L-Threo-4-hydroxyproline	ChEBI
trans-Hydroxyproline	ChEBI
trans-L-Hydroxyproline	ChEBI
L-Hydroxyproline	Kegg
trans-4-Hydroxy-L-proline	Kegg
(2S,4R)-4-Hydroxy-2-pyrrolidinecarboxylate	Generator
Δ-hydroxyproline	Generator
(2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid	HMDB
(4R)-4-Hydroxy-L-proline	HMDB
4-Hydroxy-2-pyrrolidinecarboxylic acid	HMDB
4-Hydroxy-L-proline	HMDB
4-L-Hydroxyproline	HMDB
Hydroxiproline	HMDB
Hydroxy-proline	HMDB
LS-Hydroxyproline	HMDB
Oxaceprol	HMDB
trans-4-Hydroxyproline	HMDB
4 Hydroxyproline	HMDB
Oxyproline	HMDB
(-)-4-Hydroxy-2-pyrrolidinecarboxylic acid	HMDB
(2S,4R)-(-)-4-Hydroxyproline	HMDB
(2S,4R)-4-Hydroxyproline	HMDB
(R)-4-Hydroxy-(S)-proline	HMDB
(R)-4-Hydroxy-L-proline	HMDB
(S)-Hydroxyproline	HMDB
4(R)-Hydroxy-2(S)-pyrrolidinecarboxylic acid	HMDB
4(R)-Hydroxyproline	HMDB
4-Hydroxy-(S)-proline	HMDB
4-trans-Hydroxy-L-proline	HMDB
L-Hypro	HMDB
L-trans-4-Hydroxyproline	HMDB
NSC 46704	HMDB
trans-L-4-Hydroxyproline	HMDB
4-Hydroxyproline	HMDB

Chemical Formula

C₅H₉NO₃

Average Molecular Weight

131.1299

Monoisotopic Molecular Weight

131.058243159

IUPAC Name

(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid

Traditional Name

hypro

CAS Registry Number

51-35-4

SMILES

O[C@H]1CN[C@@H](C1)C(O)=O

InChI Identifier

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

InChI Key

PMMYEEVYMWASQN-DMTCNVIQSA-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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Proline 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 Framework

Aliphatic heteromonocyclic compounds

External Descriptors

4-hydroxyproline (CHEBI:18095 )
Other amino acids (C01157 )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Cellular substructure

Extracellular (HMDB: HMDB0036576)
Cytoplasm (HMDB: HMDB0036576)

Source

Exogenous

Exogenous (HMDB: HMDB0036576)

Process

Not Available

Role

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	274 - 275 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	361 mg/mL at 25 °C	Not Available
LogP	-3.17	HANSCH,C ET AL. (1995)

Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct Type	Data Source	CCS Value (Å²)	Reference
[M-H]-	Astarita_neg	124.7	30932474
[M-H]-	MetCCS_test_neg	123.8	30932474
[M+H]+	Astarita_pos	122.3	30932474
[M+H]+	MetCCS_test_pos	128.149	30932474
[M-H]-	Not Available	125.0	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000089
[M+H]+	Not Available	128.7	http://allccs.zhulab.cn/database/detail?ID=AllCCS00000089

Predicted Molecular Properties

Property	Value	Source
Water Solubility	492 g/L	ALOGPS
logP	-3.3	ALOGPS
logP	-3.7	ChemAxon
logS	0.57	ALOGPS
pKa (Strongest Acidic)	1.64	ChemAxon
pKa (Strongest Basic)	10.62	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	69.56 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	29.38 m³·mol⁻¹	ChemAxon
Polarizability	12.29 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

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	128.831	31661259
DarkChem	[M-H]-	122.043	31661259
AllCCS	[M+H]+	129.258	32859911
AllCCS	[M-H]-	123.05	32859911
DeepCCS	[M+H]+	125.395	30932474
DeepCCS	[M-H]-	121.714	30932474
DeepCCS	[M-2H]-	159.098	30932474
DeepCCS	[M+Na]+	134.522	30932474
AllCCS	[M+H]+	129.3	32859911
AllCCS	[M+H-H2O]+	124.7	32859911
AllCCS	[M+NH4]+	133.5	32859911
AllCCS	[M+Na]+	134.7	32859911
AllCCS	[M-H]-	123.0	32859911
AllCCS	[M+Na-2H]-	125.1	32859911
AllCCS	[M+HCOO]-	127.4	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
4-Hydroxyproline	O[C@H]1CN[C@@H](C1)C(O)=O	2552.8	Standard polar	33892256
4-Hydroxyproline	O[C@H]1CN[C@@H](C1)C(O)=O	1284.4	Standard non polar	33892256
4-Hydroxyproline	O[C@H]1CN[C@@H](C1)C(O)=O	1552.1	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
4-Hydroxyproline,1TMS,isomer #1	C[Si](C)(C)O[C@H]1CN[C@H](C(=O)O)C1	1449.4	Semi standard non polar	33892256
4-Hydroxyproline,1TMS,isomer #2	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1	1354.4	Semi standard non polar	33892256
4-Hydroxyproline,1TMS,isomer #3	C[Si](C)(C)N1C[C@H](O)C[C@H]1C(=O)O	1432.0	Semi standard non polar	33892256
4-Hydroxyproline,2TMS,isomer #1	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C)CN1	1442.1	Semi standard non polar	33892256
4-Hydroxyproline,2TMS,isomer #2	C[Si](C)(C)O[C@@H]1C[C@@H](C(=O)O)N([Si](C)(C)C)C1	1471.9	Semi standard non polar	33892256
4-Hydroxyproline,2TMS,isomer #3	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1[Si](C)(C)C	1442.8	Semi standard non polar	33892256
4-Hydroxyproline,3TMS,isomer #1	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C)CN1[Si](C)(C)C	1500.8	Semi standard non polar	33892256
4-Hydroxyproline,3TMS,isomer #1	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C)CN1[Si](C)(C)C	1594.0	Standard non polar	33892256
4-Hydroxyproline,3TMS,isomer #1	C[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C)CN1[Si](C)(C)C	1683.5	Standard polar	33892256
4-Hydroxyproline,1TBDMS,isomer #1	CC(C)(C)[Si](C)(C)O[C@H]1CN[C@H](C(=O)O)C1	1682.0	Semi standard non polar	33892256
4-Hydroxyproline,1TBDMS,isomer #2	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1	1602.4	Semi standard non polar	33892256
4-Hydroxyproline,1TBDMS,isomer #3	CC(C)(C)[Si](C)(C)N1C[C@H](O)C[C@H]1C(=O)O	1698.2	Semi standard non polar	33892256
4-Hydroxyproline,2TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1	1905.5	Semi standard non polar	33892256
4-Hydroxyproline,2TBDMS,isomer #2	CC(C)(C)[Si](C)(C)O[C@@H]1C[C@@H](C(=O)O)N([Si](C)(C)C(C)(C)C)C1	1989.8	Semi standard non polar	33892256
4-Hydroxyproline,2TBDMS,isomer #3	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O)CN1[Si](C)(C)C(C)(C)C	1919.3	Semi standard non polar	33892256
4-Hydroxyproline,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1[Si](C)(C)C(C)(C)C	2197.5	Semi standard non polar	33892256
4-Hydroxyproline,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1[Si](C)(C)C(C)(C)C	2189.9	Standard non polar	33892256
4-Hydroxyproline,3TBDMS,isomer #1	CC(C)(C)[Si](C)(C)OC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1[Si](C)(C)C(C)(C)C	2100.8	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000x-0950000000-5b1c397e26b28e872d20	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000x-0950000000-c46b5bba0f41001e3c18	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-9530000000-00db00b15ab5341d7d64	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-MS (2 TMS)	splash10-0a4i-1900000000-c0a869abe2f1e9f8c08e	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-MS (3 TMS)	splash10-001l-1960000000-abcd0377696d2b52d815	2014-06-16	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline EI-B (Non-derivatized)	splash10-001i-0590000000-75e03328fb2d44469057	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Non-derivatized)	splash10-000x-0950000000-c46b5bba0f41001e3c18	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Non-derivatized)	splash10-00di-9530000000-00db00b15ab5341d7d64	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-MS (Non-derivatized)	splash10-0a4i-1900000000-c0a869abe2f1e9f8c08e	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-MS (Non-derivatized)	splash10-001l-1960000000-abcd0377696d2b52d815	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Non-derivatized)	splash10-000x-0940000000-97328204c6b60a244616	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Non-derivatized)	splash10-000x-0940000000-468aeb79950a9e6dadc6	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Experimental GC-MS	GC-MS Spectrum - 4-Hydroxyproline GC-EI-TOF (Non-derivatized)	splash10-0a4i-0900000000-40c0bfa9451caacaf422	2017-09-12	HMDB team, MONA, MassBank	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a6r-9100000000-af92b4a861832ca4ec13	2016-09-22	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (2 TMS) - 70eV, Positive	splash10-02mu-9670000000-81c8390bdfa262fa9b2f	2017-10-06	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - 4-Hydroxyproline GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	2021-11-05	Wishart Lab	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00ku-9000000000-f5bd67093b2f30a6f62b	2018-05-25	Not Available	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline Quattro_QQQ 10V, Positive-QTOF (Annotated)	splash10-0019-9700000000-ea3ed008938a57d1263c	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline Quattro_QQQ 25V, Positive-QTOF (Annotated)	splash10-014r-9000000000-0b76109525f362b600a0	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline Quattro_QQQ 40V, Positive-QTOF (Annotated)	splash10-014l-9000000000-477e41e40831316e68ac	2012-07-24	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive-QTOF	splash10-0019-9300000000-7228a10f32d447b58ee0	2012-08-31	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative-QTOF	splash10-001i-0900000000-11800ca52c6e911f8313	2012-08-31	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline LC-ESI-QTOF , negative-QTOF	splash10-001i-0900000000-11800ca52c6e911f8313	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline , negative-QTOF	splash10-001i-1900000000-b6bba00a324b6eab209f	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline , negative-QTOF	splash10-001i-1900000000-ba9df49a4d967cf8851d	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline LC-ESI-IT , positive-QTOF	splash10-000i-9000000000-6d125b0bb59101e9ce53	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline LC-ESI-QTOF , positive-QTOF	splash10-0019-9300000000-7228a10f32d447b58ee0	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline , positive-QTOF	splash10-0019-9600000000-5bcced64c9dfeb96876f	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline , positive-QTOF	splash10-0019-9600000000-b575fa8df5e2d8bb3a99	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 40V, Positive-QTOF	splash10-014l-9000000000-c036fd15ccf6ed0c554e	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 20V, Positive-QTOF	splash10-00kr-9000000000-8746de5249187bab94dc	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 40V, Positive-QTOF	splash10-014i-9000000000-3f70e8e1eef8568e87ef	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 10V, Positive-QTOF	splash10-000i-9200000000-cd32fa744ef013f5ca48	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 10V, Positive-QTOF	splash10-000i-9200000000-3ea6a86203c48888d528	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 40V, Positive-QTOF	splash10-02tc-9000000000-95aa07d1970d7f83f347	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - 4-Hydroxyproline 20V, Positive-QTOF	splash10-014r-9000000000-95b2178b5433b4b2db50	2021-09-20	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 10V, Positive-QTOF	splash10-03di-3900000000-a10576d40ff1d7fc707a	2016-09-12	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 20V, Positive-QTOF	splash10-02t9-9400000000-8b66308781907cdf6304	2016-09-12	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 40V, Positive-QTOF	splash10-014i-9000000000-7f9d42864b2decdbdd1d	2016-09-12	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 10V, Negative-QTOF	splash10-001i-2900000000-bfc9154f784caa2e61a7	2016-09-12	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 20V, Negative-QTOF	splash10-02ar-9800000000-750b3fd4f0e1dcb8ef4c	2016-09-12	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 4-Hydroxyproline 40V, Negative-QTOF	splash10-00r6-9000000000-efe39f47f6ee937ded3d	2016-09-12	Wishart Lab	View Spectrum

NMR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Experimental 1D NMR	¹³C NMR Spectrum (1D, 400 MHz, H₂O, experimental)	2021-10-10	Wishart Lab	View Spectrum
Experimental 1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	2021-10-10	Wishart Lab	View Spectrum
Experimental 2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	2012-12-05	Wishart Lab	View Spectrum

IR Spectra

Spectrum Type	Description	Deposition Date	Source	View
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)	2023-02-03	FELIX lab	View Spectrum
Predicted IR Spectrum	IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)	2023-02-03	FELIX lab	View Spectrum

Biological Properties

Cellular Locations

Mitochondria
Endoplasmic reticulum

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Saliva
Urine

Tissue Locations

Epidermis
Fibroblasts
Kidney
Liver
Pancreas
Placenta
Platelet
Prostate
Skeletal Muscle
Spleen

Pathways

Name	SMPDB/PathBank	KEGG
Prolidase Deficiency (PD)		Not Available
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)		Not Available
Hyperprolinemia Type II		Not Available
Hyperprolinemia Type I		Not Available
Prolinemia Type II		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Female	Normal	27355821	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Female	Normal	27355821	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Female	Normal	27355821	details
Blood	Detected and Quantified	<91000 uM	Infant (0-1 year old)	Female	Normal	15617190	details
Blood	Detected and Quantified	16 - 53 uM	Infant (0-1 year old)	Male	Normal	15723447	details
Blood	Detected and Quantified	11.8 (9.9-13.7) uM	Adult (>18 years old)	Both	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	40.0 (28.0-55.0) uM	Newborn (0-30 days old)	Both	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	40.0 +/- 40.0 uM	Newborn (0-30 days old)	Not Specified	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	24.0 +/- 13.0 uM	Children (1-13 years old)	Male	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	20.0 +/- 12.0 uM	Children (1-13 years old)	Female	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	20 +/- 12 uM	Children (1 - 13 years old)	Female	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	20.0 +/- 11.0 uM	Adult (>18 years old)	Male	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	16.0 +/- 9.0 uM	Adult (>18 years old)	Female	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	24 +/- 13 uM	Children (1 - 13 years old)	Male	Normal	Geigy Scientific ...	details
Blood	Detected and Quantified	13.0 (3.0-23.0) uM	Adult (>18 years old)	Both	Normal	12297216	details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Blood	Detected and Quantified	4.00-30.0 uM	Adult (>18 years old)	Both	Normal	Molecular You	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	25037050	details
Feces	Detected but not Quantified	Not Quantified	Not Specified	Both	Normal	25486321	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Normal	27609529	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	29808030	details
Feces	Detected and Quantified	10 +/- 10 nmol/g wet feces	Adult (>18 years old)	Both	Normal	27624970	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	27543620	details
Saliva	Detected and Quantified	0.873 +/- 0.537 uM	Adult (>18 years old)	Female	Normal	Sugimoto et al. (...	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Not Specified	Normal	12097436	details
Saliva	Detected and Quantified	1.5 +/- 2.6 uM	Adult (>18 years old)	Male	Normal	21164041	details
Saliva	Detected and Quantified	1.1 +/- 2.0 uM	Adult (>18 years old)	Male	Normal	21164041	details
Saliva	Detected and Quantified	0.93 +/- 0.91 uM	Adult (>18 years old)	Both	Normal	Zerihun T. Dame, ...	details
Saliva	Detected and Quantified	<0.25 uM	Adult (>18 years old)	Male	Normal	21164041	details
Saliva	Detected and Quantified	0.432 +/- 0.431 uM	Adult (>18 years old)	Male	Normal	Sugimoto et al. (...	details
Saliva	Detected and Quantified	<0.25 uM	Adult (>18 years old)	Male	Normal	21164041	details
Urine	Detected and Quantified	0.15 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	19309105	details
Urine	Detected and Quantified	497.46 +/- 203.51 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	19468821	details
Urine	Detected and Quantified	720.19 +/- 373.10 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	19468821	details
Urine	Detected and Quantified	723.58 +/- 260.04 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	19468821	details
Urine	Detected and Quantified	<2.49 umol/mmol creatinine	Adolescent (13-18 years old)	Not Specified	Normal	Mayo Clinic	details
Urine	Detected and Quantified	0.26-0.64 umol/mmol creatinine	Adult (>18 years old)	Female	Normal	27012787	details
Urine	Detected and Quantified	8.12-92.19 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	32340350	details
Urine	Detected and Quantified	28.41(16.96-78.82) umol/mmol creatinine	Newborn (0-30 days old)	Female	Normal	32340350	details
Urine	Detected and Quantified	34.65(8.07-96.55) umol/mmol creatinine	Newborn (0-30 days old)	Male	Normal	32340350	details
Urine	Detected and Quantified	<1.70 umol/mmol creatinine	Adult (>18 years old)	Not Specified	Normal	Mayo Clinic	details
Urine	Detected and Quantified	<3.289 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Not Available	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Urine	Detected and Quantified	<286.82 umol/mmol creatinine	Infant (0-1 year old)	Not Specified	Normal	Mayo Clinic	details
Urine	Detected and Quantified	1.37 +/- 0.78 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	15992788	details
Urine	Detected and Quantified	<10.067 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	Mayo Clinic	details
Urine	Detected and Quantified	0.26-0.45 umol/mmol creatinine	Adult (>18 years old)	Male	Normal	27012787	details
Urine	Detected and Quantified	186.45 (145.78-227.11) umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	Geigy Scientific ... West Cadwell, N.J... Basel, Switzerlan...	details
Urine	Detected and Quantified	< 2.0 umol/mmol creatinine	Infant (6 months - <1 year old)	Both	Normal	3168222	details
Urine	Detected and Quantified	<10.0 umol/mmol creatinine	Infant (1 - 6 months old)	Both	Normal	3168222	details
Urine	Detected and Quantified	7.5 +/- 2.9 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	3168222	details
Urine	Detected and Quantified	2 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	21388201	details
Urine	Detected and Quantified	6.5 (2.4-12.5) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	<5.20 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	Mayo Clinic	details
Urine	Detected and Quantified	4-230 umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	30830347	details
Urine	Detected and Quantified	88.17 +/- 49.59 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	2026685	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	19033659	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	19033659	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	19033659	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	19033659	details
Urine	Detected and Quantified	67.94 (43.53-132.88) umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	Analysis of 40 NI...	details
Urine	Detected and Quantified	<143 umol/mmol creatinine	Infant (0-1 year old)	Female	Normal	15617190	details
Urine	Detected and Quantified	0 - 143 umol/mmol creatinine	Infant (0-1 year old)	Male	Normal	15723447	details
Urine	Detected and Quantified	<2.15 umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	Mayo Clinic	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	25105552	details
Blood	Detected and Quantified	5.66 +/- 0.67 uM	Elderly (>65 years old)	Both	Alzheimer's disease	17031479	details
Blood	Detected and Quantified	43.8 +/- 12.5 uM	Adult (>18 years old)	Both	Hemodialysis	10838467	details
Blood	Detected and Quantified	27.0 +/- 14.1 uM	Adult (>18 years old)	Both	Hemodialysis	10838467	details
Blood	Detected and Quantified	339 uM	Infant (0-1 year old)	Male	Hydroxyprolinemia	15723447	details
Blood	Detected and Quantified	412000 uM	Infant (0-1 year old)	Female	Hydroxyprolinemia	15617190	details
Blood	Detected and Quantified	5.6 +/- 0.67 uM	Adult (>18 years old)	Both	Alzheimer's disease	17031479	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	0.28 +/- 0.055 uM	Adult (>18 years old)	Both	Alzheimer's disease	17031479	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Crohns disease	27609529	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Ulcerative colitis	27609529	details
Feces	Detected but not Quantified	Not Quantified	Children (6 - 18 years old)	Not Specified	Unclassified IBD	27609529	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal Cancer	27275383	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	25037050	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Attachment loss	31026179	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Missing teeth	31026179	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Periodontal Probing Depth	31026179	details
Saliva	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Male	Tooth Decay	31026179	details
Urine	Detected and Quantified	30.862 +/- 12.249 umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	Analysis of 30 no...	details
Urine	Detected and Quantified	0.21 +/- 0.017 umol/mmol creatinine	Adult (>18 years old)	Both	Alzheimer's disease	17031479	details
Urine	Detected and Quantified	75 (50-100) umol/mmol creatinine	Children (1-13 years old)	Both	Iminoglycinuria	MetaGene: Metabol...	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Adolescent (13-18 years old)	Both	Hyperglycinuria	19033659	details
Urine	Detected and Quantified	0 umol/mmol creatinine	Adult (>18 years old)	Both	Hyperglycinuria	19033659	details
Urine	Detected and Quantified	1957 umol/mmol creatinine	Infant (0-1 year old)	Female	Hydroxyprolinemia	15617190	details
Urine	Detected and Quantified	2960 umol/mmol creatinine	Infant (0-1 year old)	Male	Hydroxyprolinemia	15723447	details
Urine	Detected and Quantified	0-250 umol/mmol creatinine	Children (1-13 years old)	Both	Iminoglycinuria	19033659	details
Urine	Detected and Quantified	40-150 umol/mmol creatinine	Adult (>18 years old)	Female	Iminoglycinuria	19033659	details

Associated Disorders and Diseases

Disease References

Alzheimer's disease
Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. [PubMed:17031479 ]
Hemodialysis
Raj DS, Ouwendyk M, Francoeur R, Pierratos A: Plasma amino acid profile on nocturnal hemodialysis. Blood Purif. 2000;18(2):97-102. [PubMed:10838467 ]
Colorectal cancer
Ni Y, Xie G, Jia W: Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014 Sep 5;13(9):3857-70. doi: 10.1021/pr500443c. Epub 2014 Aug 14. [PubMed:25105552 ] Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ] Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Hydroxyprolinemia
la Marca G, Malvagia S, Pasquini E, Donati MA, Gasperini S, Procopio E, Zammarchi E: Hyperhydroxyprolinaemia: a new case diagnosed during neonatal screening with tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19(6):863-4. [PubMed:15723447 ] Baykal T, Karaaslan I, Gokcay G, Demir F, Laleli Y, Demirkol M: Hyperhydroxyprolinaemia detected in newborn screening with tandem mass spectrometry. J Inherit Metab Dis. 2004;27(6):781-2. [PubMed:15617190 ]
Crohn's disease
Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Ulcerative colitis
Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Attachment loss
Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
Missing teeth
Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
Periodontal Probing Depth
Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
Tooth Decay
Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
Iminoglycinuria
Broer S, Bailey CG, Kowalczuk S, Ng C, Vanslambrouck JM, Rodgers H, Auray-Blais C, Cavanaugh JA, Broer A, Rasko JE: Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. J Clin Invest. 2008 Dec;118(12):3881-92. doi: 10.1172/JCI36625. Epub 2008 Nov 6. [PubMed:19033659 ] G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Eosinophilic esophagitis
Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work). NA.

Associated OMIM IDs

104300 (Alzheimer's disease)
114500 (Colorectal cancer)
237000 (Hydroxyprolinemia)
266600 (Crohn's disease)
242600 (Iminoglycinuria)
610247 (Eosinophilic esophagitis)

External Links

DrugBank ID

DB08847

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

METLIN ID

PubChem Compound

PDB ID

Not Available

ChEBI ID

18095

Food Biomarker Ontology

Not Available

VMH ID

4HPRO_LT

MarkerDB ID

MDB00000237

Good Scents ID

Not Available

References

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)

General References

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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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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Tasanen K, Eble JA, Aumailley M, Schumann H, Baetge J, Tu H, Bruckner P, Bruckner-Tuderman L: Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15. J Biol Chem. 2000 Feb 4;275(5):3093-9. [PubMed:10652291 ]
Keskiaho K, Hieta R, Sormunen R, Myllyharju J: Chlamydomonas reinhardtii has multiple prolyl 4-hydroxylases, one of which is essential for proper cell wall assembly. Plant Cell. 2007 Jan;19(1):256-69. Epub 2007 Jan 12. [PubMed:17220203 ]
Lafranconi WM, Duhamel RC, Brendel K, Huxtable RJ: Differentiation of the cardiac and pulmonary toxicity of monocrotaline, a pyrrolizidine alkaloid. Biochem Pharmacol. 1984 Jan 15;33(2):191-7. [PubMed:6200114 ]
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ADAMS E, GOLDSTONE A, SINGH RM, ROSSO G: SUBSTRATE ACTIVITY OF 3-HYDROXYPROLINE ISOMERS FOR ENZYMES ACTIVE WITH 4-HYDROXYPROLINE. Biochim Biophys Acta. 1964 Jul 8;89:164-6. [PubMed:14212996 ]
Last JA, Reiser KM, Tyler WS, Rucker RB: Long-term consequences of exposure to ozone. I. Lung collagen content. Toxicol Appl Pharmacol. 1984 Jan;72(1):111-8. [PubMed:6710477 ]
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 ]
Burjanadze TV: New analysis of the phylogenetic change of collagen thermostability. Biopolymers. 2000 May;53(6):523-8. [PubMed:10775067 ]
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Only showing the first 10 proteins. There are 15 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details

1. D-amino-acid oxidase

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

Enzyme Details

2. Prolyl 4-hydroxylase subunit alpha-2

General function:: Involved in oxidoreductase 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:: 60632.19

Reactions

L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxide	details

Enzyme Details

3. 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

4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Ion	details
4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Ion	details

Enzyme Details

4. Prolyl 4-hydroxylase subunit alpha-1

General function:: Involved in oxidoreductase 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:: 60966.645

Reactions

L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxide	details

Enzyme Details

5. 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

4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Ion	details
4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Ion	details

Enzyme Details

6. Dipeptidyl peptidase 4

General function:: Involved in serine-type endopeptidase activity
Specific function:: Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF- kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline
Gene Name:: DPP4
Uniprot ID:: P27487
Molecular weight:: 88277.9

Enzyme Details

7. 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

Enzyme Details

8. 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

4-Hydroxyproline + NAD → Pyrroline hydroxycarboxylic acid + NADH + Hydrogen Ion	details
4-Hydroxyproline + NADP → Pyrroline hydroxycarboxylic acid + NADPH + Hydrogen Ion	details

Enzyme Details

9. Neutral amino acid transporter A

General function:: Involved in sodium:dicarboxylate symporter activity
Specific function:: Transporter for alanine, serine, cysteine, and threonine. Exhibits sodium dependence
Gene Name:: SLC1A4
Uniprot ID:: P43007
Molecular weight:: 55722.5

Enzyme Details

10. Transient receptor potential cation channel subfamily M member 1

General function:: Involved in ion channel activity
Specific function:: Cation channel essential for the depolarizing photoresponse of retinal ON bipolar cells. It is part of the GRM6 signaling cascade. May play a role in metastasis suppression. May act as a spontaneously active, calcium-permeable plasma membrane channel
Gene Name:: TRPM1
Uniprot ID:: Q7Z4N2
Molecular weight:: 182177.0

Only showing the first 10 proteins. There are 15 proteins in total.

Show all enzymes and transporters

Showing metabocard for 4-Hydroxyproline (HMDB0000725)

MOL for HMDB0000725 (4-Hydroxyproline)

3D MOL for HMDB0000725 (4-Hydroxyproline)

3D SDF for HMDB0000725 (4-Hydroxyproline)

3D-SDF for HMDB0000725 (4-Hydroxyproline)

PDB for HMDB0000725 (4-Hydroxyproline)

3D PDB for HMDB0000725 (4-Hydroxyproline)

SMILES for HMDB0000725 (4-Hydroxyproline)

INCHI for HMDB0000725 (4-Hydroxyproline)

Structure for HMDB0000725 (4-Hydroxyproline)

3D Structure for HMDB0000725 (4-Hydroxyproline)

Experimental Collision Cross Sections

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

NMR Spectra

IR Spectra

Enzymes

Reactions

Reactions

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Reactions

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