PRODUCTS

L-HYDROXYPROLINE

L-Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.
L-Hydroxyproline is used as a diagnostic marker of bone turnover and liver fibrosis.
L-Hydroxyproline enhances collagen production and skin firmness.

CAS Number: 51-35-4
EC Number: 200-091-9
Molecular Formula: C5H9NO3
Molecular Weight: 131.13

SYNONYMS:
(2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid, L-Hydroxyproline, 51-35-4, trans-4-Hydroxy-L-proline, hydroxyproline, Hypro, hydroxy-L-proline, trans-L-Hydroxyproline, L-Proline, 4-hydroxy-, (4R)-, (4R)-4-hydroxy-L-proline, trans-Hydroxyproline, 4-Hydroxy-2-pyrrolidinecarboxylic acid, delta-Hydroxyproline, L-Proline, 4-hydroxy-, trans-, RMB44WO89X, (2S,4R)-4-hydroxyproline, LUMISTOR, CHEBI:18095, L-threo-4-hydroxyproline, NSC-46704, DTXSID10883225, (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid, NSC46704, CHEBI:18240, oxyproline, NMH-Pro, cis 4 Hydroxyproline, 4 HYDROXYPROLINE, CHEBI:24741, DTXCID001022774, O Hui Wrinkle Science Wrinkle Repair, Ohui Wrinkle Science Wrinkle Repair Eye, 200-091-9, (2S,4R)-4-hydroxypyrrolidin-1-ium-2-carboxylate, (2S,4R)-4-hydroxypyrrolidinium-2-carboxylate, (2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid, L-4-hydroxyproline, trans-4-Hydroxyproline, H-Hyp-OH, 4-Hydroxy-L-proline, 4-hydroxyproline, Hydroxyproline (VAN), Ls-Hydroxyproline, Proline, 4-hydroxy-, L-, 4-L-Hydroxyproline, Proline, 4-hydroxy- (VAN), L-Proline, 4-hydroxy-, Proline, 4-hydroxy-, CHEMBL352418, 618-28-0, (2S,4R)-trans-4-hydroxyproline, MFCD00064320, (2S,4R)-rel-4-Hydroxypyrrolidine-2-carboxylic acid, Hyp, L-Proline, 4-hydroxy-, trans- (9CI), SMR000857104, trans-4-hydroxy-proline, 147028-80-6, 6912-67-0, UNII-RMB44WO89X, hydroxiproline, hydroxy-proline, H-trans-Hyp-OH, Hydroxyproline,(l), EINECS 200-091-9, L-Proline, trans-, NSC 46704, (4r)-hydroxyproline, 4(R)-hydroxyproline, (2S,4R)-(-)-4-Hydroxy-2-Pyrrolidinecarboxylic Acid, .delta.-Hydroxyproline, L-4-transhydroxyproline, trans-4-hydroxyL-proline, Trans4-hydroxy-L-proline, trans 4-hydroxy-l-proline, bmse000123, bmse000966, L-trans-4-hydroxy-proline, trans-4-hydroxy(L)proline, HYDROXYPROLINE [MI], trans-4-hydroxyl-l-proline, L-Hydroxyproline (Standard), SCHEMBL21185, MLS001332463, MLS001332464, trans-4-hydroxy-(L)-proline, (2S, 4R)-4-hydroxyproline, GTPL4704, SCHEMBL1661516, (2s,4r)-4-hydroxy-l-proline, HYDROXYPROLINE [WHO-DD], (2S, 4R)-4-hydroxy-proline, MSK1427, BDBM50357233, HY-40135R, s5820, SBB004222, trans-4-Hydroxy-L-proline, >=99%, AKOS007930607, AC-2249, CS-W008928, DB08847, FH14370, PS-5807, (2S,4R)-2-carboxy-4-hydroxypyrrolidine, BP-10638, HY-40135, NCI60_004102, DB-179157, DB-265199, DB-266976, NS00078838, EN300-53732, C01157, M03214, P16433, trans-4-Hydroxy-L-proline, analytical standard, (2S, 4R)-4-hydroxy-2-pyrrolidinecarboxylic acid, (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylic acid, 4-(R)-hydroxy-pyrrolidine-2-(S)-carboxylic acid, (2S, 4R)-4-hydroxy-2-pyrrolidine-carboxylic acid, Q27089020, trans-4-Hydroxy-L-proline, BioXtra, >=99.0% (NT), F8889-8652, Z802856442, F05487BD-FA1D-4C80-83AD-3A91E2078031, trans-4-Hydroxy-L-proline, Vetec(TM) reagent grade, 99%, L-Hydroxyproline; [2S,4R]-4-Hydroxy-2-pyrrolidinecarboxylic acid, trans-4-Hydroxy-L-proline, BioReagent, suitable for cell culture, >=98.5%, Hydroxyproline, Pharmaceutical Secondary Standard; Certified Reference Material

L-Hydroxyproline is a neutral heterocyclic protein amino acid.
L-Hydroxyproline is found in collagen and as such it is common in many gelatin products.
L-Hydroxyproline, one of the hydroxyproline (Hyp) isomers, is a useful chiral building block in the production of many pharmaceuticals.

L-Hydroxyproline is one of the non-essential amino acid.
L-Hydroxyproline is a major component of the protein collagen.
L-Hydroxyproline is vital for collagen stabiity in the body.

In combination with vitamin C can form collagen.
L-Hydroxyproline is a key amino acid derivative involved in collagen synthesis.
(2S,4R)-4-Hydroxyproline, or L-Hydroxyproline (C₅H₉O₃N), is an amino acid, abbreviated as Hyp or O, e.g., in Protein Data Bank.

L-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 L-Hydroxyproline formation.

L-Hydroxyproline is a biomarker for the consumption of processed meat.
L-Hydroxyproline 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.

L-Hydroxyproline (or hydroxyproline or Hyp) is a major component of the protein collagen.
L-Hydroxyproline is produced by hydroxylation of the amino acid proline and is, therefore, a post-translationally modified amino acid.
L-Hydroxyproline and proline play key roles for collagen stability.

In particular, they permit the sharp twisting of the collagen helix.
L-Hydroxyproline is found in few proteins other than collagen.
L-Hydroxyproline is produced by hydroxylation of the amino acid proline and is, therefore, a post-translationally modified, non-essential amino acid.

Bedridden and elderly individuals show significantly elevated serum levels of L-Hydroxyproline in comparison to normal, active individuals.
Elevated levels of urinary L-Hydroxyproline are also indicative of muscle damage.
Increased reactive oxygen species (ROS) are also known to accelerate collagen degradation.

L-Hydroxyproline levels increase in cases of depression and stress.
L-Hydroxyproline is found to be associated with Alzheimer's disease, and also hydroxyprolinemia and iminoglycinuria which are both inborn errors of metabolism.

USES and APPLICATIONS of L-HYDROXYPROLINE:
Product Applications of L-Hydroxyproline: Nutritional Supplements, Beauty & Personal Care, Sports Nutrition, Protein Shake, Pharmaceutical field, Medical Usage.
L-Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.

Therapeutically, L-Hydroxyproline is being studied as an an experimental medicine but is approved in France as a combination topical gel product called Cicactive for small, superficial wounds.
L-Hydroxyproline (trans-4-Hydroxy-L-proline) is a collagen-specific amino acid.

L-Hydroxyproline is used as a diagnostic marker of bone turnover and liver fibrosis.
L-Hydroxyproline supports skin elasticity, joint health, and tissue repair, making it widely used in:
Skincare & Cosmetics: L-Hydroxyproline enhances collagen production and skin firmness.

Nutritional Supplements: L-Hydroxyproline promotes joint, bone, and skin health.
Medical Nutrition: L-Hydroxyproline aids in wound healing and recovery.
Biomaterials & Tissue Engineering: L-Hydroxyproline is used in collagen scaffolds and research.

L-Hydroxyproline acts as regenerative agents.
L-Hydroxyproline is a common non-proteinogenic amino acid produced by hydroxylation of the amino acid proline by the enzyme prolyl hydroxylase following protein synthesis.

L-Hydroxyproline helps in the regeneration and renewal of collagen.
Used in cosmetics and personal care products.
L-Hydroxyproline is a major component of the protein collagen.

The only other mammalian protein which includes L-Hydroxyproline is elastin.
For this reason, L-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 L-Hydroxyproline have been found in Paget's disease L-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 L-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.
L-Hydroxyproline levels increase in cases of depression and stress
Hydroxyproline.

L-Hydroxyproline and proline play key roles in collagen stability.
In particular, they permit the sharp twisting of the collagen helix.
L-Hydroxyproline is found in few proteins other than collagen.

Increased serum and urine levels of L-Hydroxyproline have been found in Paget's disease (PMID: 436278 ).
L-Hydroxyproline content in biological fluids is used as a parameter of collagen catabolism, especially bone resorption or tissue degradation.

ALTERNATIVE PARENTS of L-HYDROXYPROLINE:
*L-alpha-amino acids
*Pyrrolidine carboxylic acids
*Secondary alcohols
*Amino acids
*1,2-aminoalcohols
*Monocarboxylic acids and derivatives
*Dialkylamines
*Carboxylic acids
*Azacyclic compounds
*Organopnictogen compounds
*Organic oxides
*Hydrocarbon derivatives
*Carbonyl compounds

SUBSTITUENTS of L-HYDROXYPROLINE:
*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

CATABOLISM of L-HYDROXYPROLINE:
Free L-Hydroxyproline is produced when collagen is broken down.
Two possible pathways can be used to break it down: the L-Hydroxyproline dehydrogenase (PRODH2) pathway results in the production of glycine, glyoxylate, glycolate, and oxalate, while the L-amino-acid oxidase pathway results in the production of pyrrole-2-carboxylate.
This additional source of glycine is important in young livestock as mammal milk and plant-based feed are deficient in glycine.

CLINICAL SIGNIFICANCE of L-HYDROXYPROLINE:
Proline hydroxylation requires ascorbic acid (vitamin C).
The most obvious, first effects (gingival and hair problems) of absence of ascorbic acid in humans come from the resulting defect in hydroxylation of proline residues of collagen, with reduced stability of the collagen molecule, causing scurvy.

Increased serum and urine levels of L-Hydroxyproline have also been demonstrated in Paget's disease.
Mass spectrometry analysis showed decreased amount of L-Hydroxyproline post-translational modifications in non inflamed tissue from ulcerative colitis patients when compared to tissue from donors without the disease.

OTHER HYDROXYPROLINES of L-HYDROXYPROLINE:
ISOMERS
Other hydroxyprolines also exist in nature.
The most notable one is trans-L-3-hydroxyproline (or (2S,3S)-3-hydroxyproline), produced in humans and other animals by prolyl 3-hydroxylase (EC 1.14.11.7).

Although present in much lower amounts than trans-L-4-hydroxyproline, 3-hydroxyproline is indispensable for the functioning of type IV collagen in mice.
Without it, the embryo does not survive to birth.

Intestinal bacteria produce L-Hydroxyproline epimerase, which performs a bidirectional conversion between the typical (for humans) trans-L-Hydroxyproline and cis-4-hydroxy-D-proline.

Archaea, trypanosomes, and possibly animals also perform this conversion.
cis-L-Hydroxyproline (equivalently, (2S,4S)-) is found in the toxic cyclic peptides from Amanita mushrooms (e.g., phalloidin).

Further modifications.
Diatom cell walls contain 2,3-cis-, 3,4-trans-, and 3,4-dihydroxyproline, which are postulated to have a role in silica deposition.
Trans-4-hydroxy-L-proline is an optically active form of L-Hydroxyproline having L-trans-configuration.

L-Hydroxyproline has a role as a human metabolite, a plant metabolite and a mouse metabolite.
L-Hydroxyproline is a tautomer of a trans-4-hydroxy-L-proline zwitterion.
L-Hydroxyproline is a neutral heterocyclic protein amino acid.

L-Hydroxyproline is found in collagen and as such it is common in many gelatin products.
L-Hydroxyproline is mostly used as a diagnostic marker of bone turnover and liver fibrosis.

Therapeutically, L-Hydroxyproline is being studied as an an experimental medicine but is approved in France as a combination topical gel product called Cicactive for small, superficial wounds.
L-Hydroxyproline is a metabolite found in or produced by Escherichia coli.

L-Hydroxyproline is a metabolite found in or produced by Escherichia coli.
L-Hydroxyproline has been reported in Daphnia pulex, Glycine max, and other organisms with data available.

L-Hydroxyproline is a nonessential amino acid derivative formed during post-translational protein modification through hydroxylation of the amino acid proline by the enzyme prolyl hydroxylase which requires vitamin C as a co-factor.
L-Hydroxyproline is a major component of the protein collagen and plays a key role in the stability of the collagen triple helix.

L-Hydroxyproline can be used as an indicator to determine the amount of collagen.
Increased L-Hydroxyproline levels in the urine and/or serum are normally associated with degradation of connective tissue.
Vitamin C deficiency decreases the conversion of proline to L-Hydroxyproline, which leads to reduced collagen stability.

ANIMALS, L-HYDROXYPROLINE:
COLLAGEN
L-Hydroxyproline is a major component of the protein collagen, comprising roughly 13.5% of mammalian collagen.
L-Hydroxyproline and proline play key roles in collagen stability.
They permit the sharp twisting of the collagen helix.

In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence.
This modification of the proline residue increases the stability of the collagen triple helix.

It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.

It was subsequently shown that the increase in stability is primarily through stereoelectronic effects and that hydration of the L-Hydroxyproline residues provides little or no additional stability.

NON-COLLAGEN
L-Hydroxyproline is found in few proteins other than collagen.
For this reason, L-Hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount.

However, the mammalian proteins elastin and argonaute 2 have collagen-like domains in which L-Hydroxyproline is formed.
Some snail poisons, conotoxins, contain L-Hydroxyproline, but lack collagen-like sequences.

Hydroxylation of proline has been shown to be involved in targeting Hypoxia-inducible factor (HIF) alpha subunit (HIF-1 alpha) for degradation by proteolysis.

Under normoxia (normal oxygen conditions), EGLN1 protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) and subsequent targeting for proteasome degradation.

DYRK1A, DYRK1B, protein kinase B, eEF2, IKK2, p53, FOXO3A, and CEP192 are also reportedly hydroxylated by PHD1.
p53 and MAPH6 are also hydroxylated by PHD3.
Free L-Hydroxyproline appears to be an antioxidant, like free proline.

PLANTS
L-Hydroxyproline-rich glycoproteins (HRGPs) are also found in plant cell walls.
These L-Hydroxyprolines serve as the attachment points for glycan chains which are added as post-translational modifications.

PROTISTS
L-Hydroxyproline is also found in the walls of oomycetes, fungus-like protists related to diatoms.
Phytophthora cactorum specifically produces a pathogenic protein containing L-Hydroxyproline.

STRUCTURE AND DISCOVERY of L-HYDROXYPROLINE:
In 1902, Hermann Emil Fischer isolated L-Hydroxyproline from hydrolyzed gelatin.
In 1905, Hermann Leuchs synthesized a racemic mixture of 4-hydroxyproline.
L-Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.

PRODUCTION AND FUNCTION of L-HYDROXYPROLINE:
L-Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl 4-hydroxylase following protein synthesis (as a post-translational modification).

The enzyme-catalyzed reaction takes place in the lumen of the endoplasmic reticulum.
Although it is not directly incorporated into proteins, L-Hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.

PHYSICAL and CHEMICAL PROPERTIES of L-HYDROXYPROLINE:
CAS No.: 51-35-4
EINECS No.: 200-091-9
Molecular Formula: C5H9NO3
Molecular Weight: 131.13
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]1CNC@@HC(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
Appearance: White flaky crystals or crystalline powder
Chemical formula: C5H9NO3
Molar mass: 131.131 g·mol−1
Molecular Weight: 131.13 g/mol
XLogP3-AA: -3.3
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 4

Rotatable Bond Count: 1
Exact Mass: 131.058243149 Da
Monoisotopic Mass: 131.058243149 Da
Topological Polar Surface Area: 69.6 Å²
Heavy Atom Count: 9
Formal Charge: 0
Complexity: 125
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 2
Undefined Atom Stereocenter Count: 0

Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes
Physical state: solid
Color: white
Odor: odorless
Melting point/freezing point: Melting point: 273 °C
Initial boiling point and boiling range: No data available
Flammability (solid, gas): No data available

Upper/lower flammability or explosive limits: No data available
Flash point: No data available
Autoignition temperature: does not ignite
Decomposition temperature: No data available
pH: No data available
Viscosity:
Viscosity, kinematic: No data available,
Viscosity, dynamic: No data available
Water solubility: 361,1 g/l at 25 °C
Partition coefficient: n-octanol/water: No data available

Vapor pressure: No data available
Density: No data available
Relative density: No data available
Relative vapor density: No data available
Particle characteristics: No data available
Explosive properties: No data available
Oxidizing properties: none
Other safety information: Bulk density ca.610 kg/m3

FIRST AID MEASURES of L-HYDROXYPROLINE:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation:
Fresh air.
*In case of skin contact:
Take off immediately all contaminated clothing.
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact:
Rinse out with plenty of water.
Call in ophthalmologist.
Remove contact lenses.
*If swallowed:
After swallowing:
Immediately make victim drink water (two glasses at most).
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of L-HYDROXYPROLINE:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains.
Collect, bind, and pump off spills.
Observe possible material restrictions.
Take up dry.
Dispose of properly.
Clean up affected area.

FIRE FIGHTING MEASURES of L-HYDROXYPROLINE:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2)
Foam
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of L-HYDROXYPROLINE:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection.
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of L-HYDROXYPROLINE:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed.
Dry.

STABILITY and REACTIVITY of L-HYDROXYPROLINE:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available