L-PROLINE

L-Proline is widely used as an ingredient in infusion and infant formula.
L-proline is pyrrolidine in which the pro-S hydrogen at position 2 is substituted by a carboxylic acid group. 
L-Proline is the only one of the twenty DNA-encoded amino acids which has a secondary amino group alpha to the carboxyl group. 

CAS Number: 147-85-3
Molecular Formula: C5H9NO2
Molecular Weight: 115.13
EINECS Number: 205-702-2

Synonyms:L-proline, proline, 147-85-3, L-(-)-Proline, (2S)-pyrrolidine-2-carboxylic acid, (S)-Pyrrolidine-2-carboxylic acid, 2-pyrrolidinecarboxylic acid, (-)-Proline, (-)-(S)-Proline, prolina, Prolinum, (S)-2-Pyrrolidinecarboxylic acid, (-)-2-Pyrrolidinecarboxylic acid, (S)-Proline, L-Prolin, L-alpha-Pyrrolidinecarboxylic acid, (S)-2-Carboxypyrrolidine, Prolinum [Latin], FEMA No. 3319, 2-Pyrrolidinecarboxylic acid (S)-, PRO (IUPAC abbreviation), CB 1707, AI3-26710, L-Pro, 9DLQ4CIU6V, NSC 46703, L-2-pyrrolidinecarboxylic acid, CHEBI:17203, NSC-46703, Prolin, DTXSID5044021, Prolinum (Latin), (2S)-pyrrolidin-1-ium-2-carboxylate, CHEBI:26271, l proline, NSC46703, pyrrolidin-1-ium-2-carboxylate, DTXCID3024021, 205-702-2, 925-434-6, H-Pro-OH, L-Pyrrolidine-2-carboxylic acid, Prolina [Spanish], Proline L-, Proline (VAN), Proline [USAN:INN], (L)-PROLINE, MFCD00064318, FEMA Number 3319, (S)-(-)-Proline, HSDB 1210, 37159-97-0, pro, CHEMBL54922, 4305-67-3, Proline (L-Proline), Carboxypyrrolidine, L-(2,3-3H)Proline, Proline (USP), L-Proline labeled with carbon-14, EINECS 205-702-2, UNII-9DLQ4CIU6V, racemic proline, rac-proline, s-proline, 3h-l-proline, Proline (S)-pyrrolidine-2-carboxylic acid (-)-2-Pyrrolidinecarboxylic acid (-)-Proline (S)-(-)-Proline (S)-2-Carboxypyrrolidine (S)-2-Pyrrolidinecarboxylic acid (S)-Proline 2-Pyrrolidinecarboxylic acid Carboxypyrrolidine L-(-)-Proline L-Pyrrolidine-2-carboxylic acid L-alpha-Pyrrolidinecarboxylic acid NSC 46703, H-Pro, (2S)-proline, Pro-OH, Enalapril Impurity 8, L-Pro-OH, (-)-Proline (S)-2-Carboxypyrrolidine, L-Proline (Standard), 2-Pyrrolidinecarboxylate, L-Proline (JP18), PROLINE [VANDF], PROLINE [HSDB], PROLINE [USAN], PROLINE [INN], PROLINE [II], PROLINE [MI], L-PROLINE [FCC], L-PROLINE [JAN], PROLINE [MART.], L-PROLINE [FHFI], PROLINE [WHO-DD], bmse000047, bmse000947, EC 205-702-2, (2S)-2-carboxypyrrolidine, SCHEMBL7792, L-PROLINE [USP-RS], (S)-2-Pyrralidinecarboxylate, (S)-2-Pyrrolidinecarboxylate, (-)-2-Pyrrolidinecarboxylate, PROLINE [EP MONOGRAPH], (S)-(-)-PROLIN, GTPL3314, orb1304741, SCHEMBL1118749, SCHEMBL1663681, SCHEMBL6001866, PROLINE [USP MONOGRAPH], HY-Y0252R, L-Proline 99% FCC FG, MSK1415, (S)-2-Pyrralidinecarboxylic acid, pyrrolidin-2-(S)-carboxylic acid, Pharmakon1600-01301007, pyrrolidine-2-(S)-carboxylic acid, BCP25292, HY-Y0252, (S)-pyrrolidine-2-carboxylic acid, L-Proline >=99.0% (NT), (S)-(-)-Pyrrolidine-2-carboxylate, BDBM50000100, NCGC00014017, NSC760114, s5629, AKOS010372120, AKOS015856025, CCG-214709, CS-W019861, DB00172, FP02713, NSC-760114, (S)-(-)-Pyrrolidine-2-carboxylic acid, NCGC00014017-02, NCGC00014017-03, NCGC00097126-01, AC-11190, AS-10803, SY001305, L-Proline BioUltra >=99.5% (NT), DB-029981, L-Proline SAJ special grade >=99.0%, L-Proline Vetec(TM) 98.5-101.5%, NS00074201, P0481, EN300-52624, L-Proline Vetec(TM) reagent grade >=99%, C00148, D00035, L-Proline ReagentPlus(R) >=99% (HPLC), M02947, P17692, BRD-K01666412-001-02-0, L-Proline certified reference material TraceCERT(R), Q20035886, A01B5B63-CC3D-4796-A7B4-C2DE26A6FA93, F0001-2348, Proline European Pharmacopoeia (EP) Reference Standard, Z756429958, L-Proline United States Pharmacopeia (USP) Reference Standard, L-Proline Pharmaceutical Secondary Standard Certified Reference Material, L-Proline from non-animal source meets EP USP testing specifications suitable for cell culture, L-Proline ,L-2-Pyrrolidinecarboxylic acid, L-PROLINE, NATURAL, L-PROLINE, SYNTHETIC, L-(-)-PROLINE ((S)-(-)-PROLINE), L-PROLINE (13C5, 99%), L-PROLINE (13C5, 99%, L-PROLINE (D7, 97-98%), L(-)-Proline 0

L-Proline, an amino acid, is colorless to white crystal or crystalline powder that has a slight, characteristic odor with a slightly sweet taste. 
L-Proline is soluble in water, insoluble in ethanol, diethyl ether and n-butanol, yellow in case of hydrated ninhydrin test solution, glacial acetic acid Red after acidification,  pH=6.3, decomposition point is 220-222°C,  specific optical rotation [α]20D-85° (0.5-2.0mg/ml, H2O), [α]20D-60.4° (0.5-2.0mg /ml, 5mol/LHCl). 
L-Proline is synthesized from L-glutamine and L-glutamate via L-ornithine in intestine, and from L-ornithine in liver. 

L-Proline is an essential component of collagen and is important for proper functioning of joints and tendons. 
L-Proline also helps maintain and strengthen heart muscles. 
L-Proline has a role as a micronutrient, a nutraceutical, an algal metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, a mouse metabolite and a member of compatible osmolytes. 

L-Proline is a glutamine family amino acid, a proteinogenic amino acid, a proline and a L-alpha-amino acid. 
It is a conjugate base of a L-prolinium. 
L-Proline is a conjugate acid of a L-prolinate. 

L-Proline is an enantiomer of a D-proline. 
L-Proline is a tautomer of a L-proline zwitterion.
L-Proline is a naturally occurring amino acid that plays a critical role in the structure and stability of proteins, especially collagen, which is the most abundant protein in connective tissues such as skin, cartilage, and bone. 

Unlike most other amino acids, L-Proline is unique because its side chain bonds back to the amino group, forming a cyclic structure that restricts flexibility and gives proteins a more rigid framework. 
This ring structure is essential for maintaining the triple-helix shape of collagen, which provides strength and resilience to tissues.
L-Proline is an amino acid, or a building block for protein. 

The body can make proline on its own, but it is also consumed in the diet. 
A typical diet contains about 5 grams of proline daily. 
The primary sources are protein-rich foods including meat, fish, and dairy. Proline can also be taken as a supplement.

L-Proline is used for skin healing, especially in people who have problems keeping enough proline in the body. 
It is also used for other conditions, but there is no good scientific evidence to support any of these uses.
In medicine, proline is used as a stabilizer to help some prescription products last longer.

Reported found as a component in many proteins,  also widely occurring as the free acid in natural products. 
A major constituent of collagen, the main fibrous protein found in bone, cartilage and other connective tissue.
L-Proline is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group -NH2 but is rather a secondary amine. 

The secondary amine nitrogen is in the protonated form (NH2+) under biological conditions, while the carboxyl group is in the deprotonated −COO− form. 
The "side chain" from the α carbon connects to the nitrogen forming a pyrrolidine loop, classifying it as a aliphatic amino acid. 
L-Proline is non-essential in humans, meaning the body can synthesize it from the non-essential amino acid L-glutamate. 

L-Proline is encoded by all the codons starting with CC (CCU, CCC, CCA, and CCG).
L-Proline is the only proteinogenic amino acid which is a secondary amine, as the nitrogen atom is attached both to the α-carbon and to a chain of three carbons that together form a five-membered ring.
L-Proline is one of the twenty amino acids used in living organisms as the building blocks of proteins. Proline is sometimes called an imino acid, although the IUPAC definition of an imine requires a carbon-nitrogen double bond. Proline is a non-essential amino acid that is synthesized from glutamic acid. 

L-Proline is an essential component of collagen and is important for proper functioning of joints and tendons.
L-Proline is a cyclic, non-essential, hydrophobic amino acid. 
L-Proline is a proteinogenic amino acid which is crucial for primary metabolism. 

In peptide chains, proline residues confer structural constraints and enhance the susceptibility of proximal peptide bonds to protease activity.
L-proline, also known as L-pyrrolidine-2-carboxylic acid, is a neutral amino acid. 
Although proline is classified as an amino acid, it is strictly speaking an imino acid, since it contains an imino group (carbon-nitrogen double bond). 

Due to its cyclic pyrrolidine side chain it is classified as a nonpolar aliphatic amino acid.
L-Proline was first isolated in 1900 by Richard Willstätter who obtained the amino acid while studying N-methylproline, and synthesized proline by the reaction of sodium salt of diethyl malonate with 1,3-dibromopropane. 
The next year, Emil Fischer isolated proline from casein and the decomposition products of γ-phthalimido-propylmalonic ester, and published the synthesis of proline from phthalimide propylmalonic ester.

The amino acid L-proline is considered to be nonessential because humans and other animals can biosynthesize it, mainly from another nonessential amino acid L-glutamic acid. 
L-Proline is unusual in that it is heterocyclic, and thus is the only natural amino acid that contains a secondary amine group, only the L-enantiomer is found in nature.
L-Proline also is unusual because it was synthesized before it was isolated from natural sources. 

In 1900, chemistry Nobel Prize–winning German chemist Richard M. Willstätter prepared the D,L-racemate from N-methylproline. 
The following year, Emil Fischer, another German Nobel laureate, isolated the L-form from egg albumen and hydrolyzed casein.
L-Proline, like all natural amino acids, is used for biosynthesizing proteins. 

The rigid five-membered ring in proline gives proteins made from it significantly different secondary structures from proteins made from open-chain proteins.
L-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.
L-Proline is a major amino acid found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. 

L-Proline is also essential for the immune system, and for necessary balance of this formula. 
L-Proline is an essential component of collagen and is important for proper functioning of joints and tendons. 
L-Proline is extremely important for the proper functioning of joints and tendons. 

Melting point: 228 °C (dec.) (lit.)
Boiling point: 215.41 °C (rough estimate)
Alpha (optical rotation): -85.5° (c = 4, H2O)
Bulk density: 500 kg/m³
Density: 1.35 g/cm³
Vapor pressure: 0 Pa at 25 °C
FEMA number: 3319 | L-Proline
Refractive index: -85° (C = 4, H2O)
Storage temperature: 2–8 °C
Solubility: H2O: 50 mg/mL
Form: Powder
pKa: 1.95, 10.64 (at 25 °C)
Color: White
pH: 6.0–7.0 (25 °C, 1M in H2O)
Odor: Odorless at 100%
Odor type: Odorless
Biological source: Synthetic
Optical activity: [α]²⁰/D 85.0 ± 1.0°, c = 5% in H2O
Water solubility: Soluble
Sensitive: Hygroscopic
UV absorption (λmax): λ: 260 nm, Amax: 0.05; λ: 280 nm, Amax: 0.05

L-Proline is considered a non-essential amino acid as it can be synthesised from arginine via the urea cycle in liver, and from glutamine/glutamic acid in the intestinal epithelium. 
L-Proline has a number of beneficial properties including connective tissue strengthening, Stronger Connective Tissue, Decreased Risk Of Heart Disease, Maintenance Of Muscle Tissueand skin health.
L-Proline is a non-essential amino acid, which is a building block of proteins. 

Peptides bond to proline, making it a useful building block for proteins. 
L-Proline can be used as a cell culture media component for the commercial biomanufacturing of therapeutic recombinant proteins and monoclonal antibodies. 
L-Proline plays important roles in various biological processes. 

L-Proline is involved in the synthesis of collagen, which is one of the most abundant proteins in the human body and provides structural support to tissues such as skin, bone, cartilage, and tendons.
Direct fermentation using analogue-resistant mutants of coryneform bacteria or Serratia marcescens is an economic production method. 
An isoleucine auxotrophic mutant of Brevibacterium flavum having resistance to sulfaguanidine and D,L-3,4-dehydroproline (DP) is able to accumulate 40 g/L L-proline. 

Brevibacterium flavum AP113 is claimed to produce 97.5 g/L L-proline,  this mutant is characterized by isoleucine auxotrophy, resistance to DP, and osmotic pressure and incapable to degrade Lproline. 
A proline oxidase-less strain of Serratia marcescens, having resistance to DP, thiazoline-4-carboxylate and azetidine-2-carboxylate, overproduces 58.5 g/L L-proline into the culture medium. 
By amplification of the genes proA and proB in this type of regulatory mutant, a construct was obtained which yields 75 g/L L-proline.

Synthesis of L-proline: Using glutamic acid as a raw material, it is esterified with absolute ethanol under the catalysis of sulfuric acid, and triethanolamine is added to free the aminosulfate to obtain glutamic acid-δ-ethyl ester. 
The glutamic acid-δ-ethyl ester is then reduced with a metal reducing agent potassium borohydride to obtain crude proline, which is finally separated and purified to obtain crude L-proline.

L-Proline is biosynthetically derived from the amino acid L-glutamate. 
L-Proline is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). 
This can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into ornithine by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline.

L-Proline has been found to act as a weak agonist of the glycine receptor and of both NMDA and non-NMDA (AMPA/kainate) ionotropic glutamate receptors.
L-Proline has been proposed to be a potential endogenous excitotoxin.
In plants, proline accumulation is a common physiological response to various stresses but is also part of the developmental program in generative tissues (e.g. pollen).

The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids. 
L-Proline also affects the rate of peptide bond formation between proline and other amino acids. 
When proline is bound as an amide in a peptide bond, its nitrogen is not bound to any hydrogen, meaning it cannot act as a hydrogen bond donor, but can be a hydrogen bond acceptor.

Peptide bond formation with incoming Pro-tRNAPro in the ribosome is considerably slower than with any other tRNAs, which is a general feature of N-alkylamino acids.
Peptide bond formation is also slow between an incoming tRNA and a chain ending in proline,  with the creation of proline-proline bonds slowest of all.
The exceptional conformational rigidity of proline affects the secondary structure of proteins near a proline residue and may account for proline's higher prevalence in the proteins of thermophilic organisms. 

Protein secondary structure can be described in terms of the dihedral angles φ, ψ and ω[broken anchor] of the protein backbone. 
The cyclic structure of proline's side chain locks the angle φ at approximately −65°.
L-Proline acts as a structural disruptor in the middle of regular secondary structure elements such as alpha helices and beta sheets,  however, proline is commonly found as the first residue of an alpha helix and also in the edge strands of beta sheets. 

L-Proline is also commonly found in turns (another kind of secondary structure), and aids in the formation of beta turns. 
This may account for the curious fact that proline is usually solvent-exposed, despite having a completely aliphatic side chain.
Multiple prolines and/or hydroxyprolines in a row can create a polyproline helix, the predominant secondary structure in collagen. 

The hydroxylation of proline by prolyl hydroxylase (or other additions of electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen significantly.
Hence, the hydroxylation of proline is a critical biochemical process for maintaining the connective tissue of higher organisms. 
Severe diseases such as scurvy can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate (vitamin C) cofactor.

The body uses L-Proline to make proteins, such as collagen, collagen is found in the skin, bones, and joints. 
L-Proline is also involved in the general function of cells.
In biological systems, L-Proline is considered a non-essential amino acid, meaning the human body can synthesize it on its own from other precursors, such as glutamate, without the need for dietary intake. 

However, consuming foods rich in proline, such as dairy products, eggs, meat, and soy, can support healthy collagen production and overall tissue repair. 
In addition to its structural role, L-Proline participates in metabolic pathways, including energy production and antioxidant defense, by contributing to the synthesis of compounds like hydroxyproline and polyamines.
Because of these properties, L-Proline is widely studied and applied in medicine, nutrition, and biotechnology. 

L-Proline is often used as a supplement to promote joint health, skin elasticity, and wound healing, since higher collagen synthesis is associated with better tissue regeneration. 
In pharmaceutical and laboratory settings, L-Proline is also used as a chiral building block for synthesizing drugs, peptides, and other bioactive molecules, due to its ability to influence stereochemistry in chemical reactions.

Uses:
L-Proline is used as asymmetric catalysts in organic synthesis and asymmetric aldol cyclization. 
L-Proline is involved in the Michael addition of dimethyl malonate to alfa-beta-unsaturated aldehydes. 
L-Proline is a precursor of hydroxyproline in collagen. 

L-Proline is an active component of collagen and involved in the proper functioning of joints and tendons. 
L-Proline finds uses in pharmaceutical, biotechnological applications due to its osmoprotectant property. 
Further, it is used with ninhydrin in the chromatography.

L-Proline is an amino acid and precursor (with vitamin C) for collagen, the building block of the structure of tendons, ligaments, arteries, veins and muscles. 
L-Proline is important in wound healing.
L-Proline has a wide range of uses in biology, medicine, industry, and research because of its special structural properties and its central role in protein stability. 

One of its most important uses is in medical and nutritional supplements, where it is included to support collagen production, skin health, joint function, and wound healing. 
Since collagen is vital for maintaining the strength and elasticity of connective tissues, L-Proline supplementation is often recommended in formulations aimed at slowing skin aging, improving flexibility in tendons and ligaments, and assisting in recovery from injuries.
In the pharmaceutical field, L-Proline is used as a chiral building block and a precursor in the synthesis of peptides, drugs, and bioactive molecules. 

Its rigid cyclic structure makes it valuable for controlling stereochemistry in chemical reactions, which is particularly important in the production of enantiomerically pure drugs. 
Many research laboratories also use L-Proline in peptide synthesis protocols, where it helps create stable conformations and influences the biological activity of the resulting compounds.
L-Proline is also widely used in the food and cosmetic industries. In food products, it can be used as a flavor enhancer and stabilizer, especially in baked goods and dairy, where it contributes to the Maillard reaction and improves taste and aroma. 

In cosmetics, it is often added to creams, serums, and anti-aging formulations because it stimulates collagen renewal, promotes hydration, and enhances skin elasticity, making it valuable in products that target wrinkles, dryness, or loss of firmness.
Another important use is in biotechnology and research, where L-Proline is employed as a cryoprotectant to protect cells, proteins, and tissues from damage during freezing and thawing. 
L-Proline is also used in cell culture media to improve the growth and stability of mammalian cells, particularly those that require collagen support. 

Additionally, scientists study L-Proline in stress physiology, since it is known to accumulate in plants and microorganisms under stress conditions, helping them adapt to drought, salinity, or oxidative stress.
L-Proline is not only used as a dietary supplement for skin, joints, and wound healing but also as an essential component in medical treatments that focus on tissue repair and recovery. 
Since proline is one of the most abundant amino acids in collagen, it is often incorporated into therapeutic formulations for patients recovering from surgeries, burns, or connective tissue injuries. 

Some specialized medical nutrition products contain L-Proline because it accelerates fibroblast activity, enhances new tissue growth, and supports the regeneration of cartilage. 
Beyond structural health, research suggests that L-Proline may play a role in cardiovascular protection by influencing arterial wall elasticity and helping to reduce the risk of conditions related to vascular stiffness.
In the pharmaceutical industry, L-Proline has become an important chiral catalyst in asymmetric synthesis. 

This means it helps create molecules with specific three-dimensional arrangements, which is critical in drug design where even small structural differences can drastically alter a drug’s effectiveness or safety. 
L-Proline and its derivatives are widely studied as "organocatalysts," making them environmentally friendly alternatives to metal-based catalysts in organic chemistry. 
They are used in producing antiviral drugs, antibiotics, and other biologically active compounds. 

Because of its stable cyclic structure, L-Proline also improves the folding of therapeutic peptides, ensuring they maintain the proper shape required for biological activity.
L-Proline has a significant role in plant biology as a stress-protective molecule. 
L-Proline accumulates in plants when they are exposed to drought, salinity, extreme temperatures, or heavy metals, acting as an osmoprotectant that stabilizes proteins, membranes, and enzymes under stress conditions. 

Because of this, agricultural scientists use L-Proline as a biostimulant to improve crop resilience. 
When applied as a foliar spray or soil amendment, it can enhance seed germination, improve root development, and increase resistance to environmental stressors, leading to better yields in challenging conditions. 
In modern sustainable agriculture, L-Proline is being tested as a natural growth enhancer to reduce dependence on chemical fertilizers and improve plant recovery after stress events.

Safety Profile:
L-Proline is a naturally occurring amino acid found in proteins and collagen, so in normal dietary amounts or when used in supplements, it is considered safe for humans. 
However, when handled in pure powdered or crystalline form in industrial or research environments, it can present some occupational hazards such as inhalation of fine dust, accidental ingestion, or eye and skin irritation.

If L-Proline dust becomes airborne, workers may accidentally inhale it, which could cause respiratory irritation, coughing, or throat discomfort. 
While it is not classified as toxic, repeated inhalation of high concentrations may lead to mild inflammation of the respiratory tract. 
Laboratories and factories that handle large amounts of L-Proline often recommend using dust masks or localized ventilation to avoid unnecessary exposure.

In concentrated forms, contact with the eyes may cause mild irritation, redness, or discomfort due to the crystalline nature of the substance. 
Direct skin contact is generally not dangerous but could occasionally lead to dryness or minor irritation, especially in individuals with sensitive skin. 
Prolonged or repeated handling without protective gloves may increase the risk of mild dermatitis.