ContaminantDB: 4-Hydroxyproline

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (1)XML

Record Information

Version

1.0

Creation Date

2014-08-29 06:51:06 UTC

Update Date

2026-04-17 17:23:59 UTC

Accession Number

CHEM003373

Identification

Common Name

4-Hydroxyproline

Class

Small Molecule

Description

4-Hydroxyproline (or 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 amino acid. Hydroxyproline and proline play key roles for 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 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 Elevated levels of urinary hydroxyproline are also indicative of muscle damage Increased reactive oxygen species (ROS) are also known to accelerate collagen degradation. Hydroxyproline levels increase in cases of depression and stress (1, 2, 3, 4).

Contaminant Sources

Cosmetic Chemicals
EAFUS Chemicals
FooDB Chemicals
HMDB Contaminants - Urine
T3DB toxins

Contaminant Type

Amine
Animal Toxin
Drug
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

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 Mass

131.130 g/mol

Monoisotopic Mass

131.058 g/mol

CAS Registry Number

51-35-4

IUPAC Name

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

Traditional Name

hypro

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 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Endoplasmic reticulum
Membrane
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

Fibroblasts
Gingiva
Kidney
Liver
Muscle
Pancreas
Placenta
Platelet
Prostate
Skeletal Muscle
Skin
Spleen

Pathways

Name	SMPDB Link	KEGG Link
Iminoglycinuria	SMP00193	Not Available
Prolinemia Type II	SMP00208	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	274 - 275°C
Boiling Point	Not Available
Solubility	361 mg/mL at 25°C

Predicted 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	1	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
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000x-0950000000-5b1c397e26b28e872d20	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-000x-0950000000-c46b5bba0f41001e3c18	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-00di-9530000000-00db00b15ab5341d7d64	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0a4i-1900000000-c0a869abe2f1e9f8c08e	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-001l-1960000000-abcd0377696d2b52d815	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-001i-0590000000-75e03328fb2d44469057	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000x-0950000000-c46b5bba0f41001e3c18	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9530000000-00db00b15ab5341d7d64	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0a4i-1900000000-c0a869abe2f1e9f8c08e	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-001l-1960000000-abcd0377696d2b52d815	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000x-0940000000-97328204c6b60a244616	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000x-0940000000-468aeb79950a9e6dadc6	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0900000000-40c0bfa9451caacaf422	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a6r-9100000000-af92b4a861832ca4ec13	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-02mu-9670000000-81c8390bdfa262fa9b2f	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0019-9700000000-ea3ed008938a57d1263c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-014r-9000000000-0b76109525f362b600a0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-014l-9000000000-477e41e40831316e68ac	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-0019-9300000000-7228a10f32d447b58ee0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-001i-0900000000-11800ca52c6e911f8313	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-001i-0900000000-11800ca52c6e911f8313	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-001i-1900000000-b6bba00a324b6eab209f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-001i-1900000000-ba9df49a4d967cf8851d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , positive	splash10-000i-9000000000-6d125b0bb59101e9ce53	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0019-9300000000-7228a10f32d447b58ee0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0019-9600000000-5bcced64c9dfeb96876f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0019-9600000000-b575fa8df5e2d8bb3a99	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-014l-9000000000-c036fd15ccf6ed0c554e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-00kr-9000000000-8746de5249187bab94dc	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-014i-9000000000-3f70e8e1eef8568e87ef	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-000i-9200000000-cd32fa744ef013f5ca48	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-000i-9200000000-3ea6a86203c48888d528	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-02tc-9000000000-95aa07d1970d7f83f347	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-014r-9000000000-95b2178b5433b4b2db50	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-3900000000-a10576d40ff1d7fc707a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-02t9-9400000000-8b66308781907cdf6304	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-014i-9000000000-7f9d42864b2decdbdd1d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-2900000000-bfc9154f784caa2e61a7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-02ar-9800000000-750b3fd4f0e1dcb8ef4c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00r6-9000000000-efe39f47f6ee937ded3d	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00ku-9000000000-f5bd67093b2f30a6f62b	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,1H] 2D NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB08847

HMDB ID

HMDB0000725

FooDB ID

FDB013511

Phenol Explorer ID

Not Available

KNApSAcK ID

BiGG ID

BioCyc ID

METLIN ID

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

ECMDB ID

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.

MSDS

Link

General References

1. Mung D, Li L: Development of Chemical Isotope Labeling LC-MS for Milk Metabolomics: Comprehensive and Quantitative Profiling of the Amine/Phenol Submetabolome. Anal Chem. 2017 Apr 18;89(8):4435-4443. doi: 10.1021/acs.analchem.6b03737. Epub 2017 Mar 28.

2. Mung D, Li L: Applying quantitative metabolomics based on chemical isotope labeling LC-MS for detecting potential milk adulterant in human milk. Anal Chim Acta. 2018 Feb 25;1001:78-85. doi: 10.1016/j.aca.2017.11.019. Epub 2017 Nov 14.

3. Kurt J. Boudonck, Matthew W. Mitchell, Jacob Wulff and John A. Ryals. Characterization of the biochemical variability of bovine milk using metabolomics. Metabolomics (2009) 5:375?386

4. Characterization of the biochemical variability of bovine milk using metabolomics

5. A. Foroutan et al. The Chemical Composition of Commercial Cow's Milk (in preparation)

6. 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.

7. Matsuda Y, Matsumoto K, Yamada A, Ichida T, Asakura H, Komoriya Y, Nishiyama E, Nakamura T: Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology. 1997 Jul;26(1):81-9.

8. Seibel MJ, Woitge HW: Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitom. 1999 Fall;2(3):299-321.

9. Kelleher PC: Urinary excretion of hydroxyproline, hydroxylysine and hydroxylysine glycosides by patients with Paget's disease of bone and carcinoma with metastases in bone. Clin Chim Acta. 1979 Mar 15;92(3):373-9.