Absorption, Distribution and Excretion
L-proline is absorbed via the gastrointestinal tract. Ingested dietary protein is denatured due to the low pH in the stomach. This denaturation and unfolding makes the protein chains more susceptible to hydrolysis by proteases. Up to 15% of dietary protein can be hydrolyzed into peptides and amino acids by pepsin in the stomach. In the duodenum and small intestine, digestion continues by hydrolytic enzymes such as trypsin, chymotrypsin, elastase, and carboxypeptidase. The resulting mixture of peptides and amino acids is then transported to mucosal cells via specific carrier systems for amino acids, dipeptides, and tripeptides. The digestive products are rapidly absorbed. Like other amino acids, L-proline is absorbed in the ileum and distal jejunum.
Absorbed peptides are further hydrolyzed to produce free amino acids, which are secreted into the portal blood via specific carrier systems within mucosal cells. Alternatively, they are metabolized intracellularly. Absorbed amino acids enter the liver, where some are utilized. The remaining amino acids enter systemic circulation and are utilized by peripheral tissues. L-proline is transported from the intestinal mucosal surface to the serosa via active transport. Its absorption mechanism is ion gradient absorption. The absorption of all L-amino acids occurs via a sodium-dependent carrier-mediated process. This transport depends on energy provided by ATP. The reported concentration of L-proline in the plasma of normal subjects is approximately 168 μM/L ± 60 mM/L, measured in plasma samples collected from healthy volunteers after an overnight fast. Like most nutrients, the concentration of L-proline in plasma is regulated by homeostasis. Various hormones (e.g., thyroid hormones, catecholamines, and growth hormone) can affect plasma amino acid levels in disease states. However, their effects are likely negligible in physiological states. Nevertheless, the antagonistic hormone system of cortisol and glucagon can affect blood levels of amino acids involved in gluconeogenesis, such as L-proline. Because amino acids filtered by the kidneys are actively reabsorbed, the loss of amino acids in the body is minimal. Loss through the skin is also negligible. Since mammals lack long-term storage mechanisms for amino acids, excess amino acids are degraded, primarily in the liver. Amino acid metabolism involves the removal of the amino group, which is then converted into urea and excreted in urine. After amino removal, the remaining amino acids can serve as an energy source or be used to synthesize other endogenous substances. /Amino Acids/

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Metabolism/Metabolites
Liver
L-proline, like several other amino acids, follows the same metabolic pathway. Therefore, L-proline metabolism is described by the entire metabolic pathway. This pathway (also known as "ornithine and proline metabolism") describes the co-metabolism of arginine, ornithine, proline, citrulline, and glutamate in the human body. Arginine is synthesized from citrulline by the successive action of the cytoplasmic enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL). Citrulline can be derived from ornithine through the catabolism of proline or glutamine/glutamate. Many of the reactions required for the production of proline and glutamate from ornithine are located in the mitochondria. Proline is biosynthesized from glutamate and its direct precursor 1-pyrroline-5-carboxylic acid. The metabolic pathway between arginine, glutamine, and proline is bidirectional. Therefore, the net utilization or production of these amino acids is highly dependent on cell type and developmental stage. At a systemic level, arginine synthesis primarily occurs via the gut-kidney axis. Small intestinal epithelial cells mainly utilize glutamine and glutamate to synthesize citrulline, working in conjunction with proximal renal tubular cells, which absorb citrulline from the bloodstream and convert it into arginine, which then returns to the bloodstream. Therefore, impaired small intestinal or renal function reduces endogenous arginine synthesis, thereby increasing dietary requirements. Proline and arginine are both essential amino acids for protein synthesis, incorporated into proteins via prolyl-tRNA and arginyl-tRNA, respectively, which are synthesized by their respective tRNA synthases. Arginine can also serve as a precursor for creatine and phosphocreatine synthesis via the intermediate guanidinoacetic acid. Ornithine is a key component of the arginine/proline metabolic pathway. In small intestinal epithelial cells, ornithine is mainly used to synthesize citrulline and arginine; in hepatocytes around the portal vein, ornithine mainly serves as an intermediate in the urea cycle; in hepatocytes around the central vein, ornithine is used to synthesize glutamate and glutamine; and in many peripheral tissues, ornithine is used to synthesize glutamate and proline.

Toxicity Summary
Identification and Uses: L-proline is a solid. It is used in biochemical and nutritional research, microbiological assays, culture media, laboratory reagents, and dietary supplements. It is also used in injectable or infusion formulations. Human Exposure and Toxicity: No relevant data are currently available. Animal Studies: In a 30-day study, a group of seven female rats drank water containing 50 mg/kg body weight of L-proline daily. Ten rats served as a control group. After 30 days, all animals were weighed, dissected, and subjected to a comprehensive gross examination. Histopathological and microscopic examinations were performed on the liver and kidneys. Serum samples were collected to determine enzyme activity and creatinine and total protein concentrations. No treatment-related effects were observed in rats administered 50 mg/kg body weight of L-proline daily compared to the control group. Among 20 common amino acids, only proline enhanced the mutagenic activity of Salmonella Typhimurium TA98 as measured in rat liver microsomes. In Salmonella Typhimurium reversion mutation assays, L-proline at concentrations up to 1000 mg/mL, regardless of metabolic activation, did not exhibit reversion mutations in various Salmonella Typhimurium strains (TA92, TA97, TA98, TA100, TA102, TA1530, TA1531, TA1532, TA1535, TA1537, TA1538, and TA1964). Ecotoxicity studies showed that proline-treated plants exhibited higher activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in their roots and leaves compared to cadmium-treated plants. Proline plays a crucial role in plant responses to various environmental stresses. For example, proline supplementation can mitigate the harmful effects of cadmium stress on young olive trees. In the kidneys, proline undergoes ring-opening oxidation by L-proline oxidase to produce L-glutamate, which participates in glycogen synthesis. L-Ornithine and L-glutamate are converted to L-proline via L-glutamate-γ-semialdehyde. L-proline is abundant in collagen and is closely related to the function of joints and tendineae.

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Interactions
Proline plays an important role in plant responses to various environmental stresses. However, its mechanism of action in alleviating heavy metal stress in plants remains unclear. This study investigated the alleviating effect of exogenous proline (10 and 20 mM) on cadmium-induced growth inhibition in young olive trees (Olea europaea L. cv. Chemlali). Soil cadmium concentrations were 10 and 30 mg CdCl₂/kg, respectively. Cadmium treatment led to significant accumulation of cadmium in root and leaf tissues and reduced gas exchange, photosynthetic pigment content, absorption of essential elements (Ca, Mg, and K), and plant biomass. Furthermore, elevated antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase) and proline content were observed, accompanied by higher levels of hydrogen peroxide, thiobarbituric acid reactants, and electrolyte leakage. Notably, the application of exogenous proline mitigated oxidative damage caused by cadmium accumulation. Indeed, cadmium-stressed olive plants treated with proline exhibited increased antioxidant enzyme activity, photosynthetic activity, nutrient status, plant growth, and olive oil content. Overall, proline supplementation appeared to alleviate the detrimental effects of cadmium stress on young olive plants. This study investigated the ability of exogenous compatible solutes (such as proline) to counteract the inhibitory effects of cadmium (Cd) on young date palm (Phoenix dactylifera L. cv Deglet Nour) plants. Two-year-old date palm plants were treated for five months with different levels of cadmium stress (0, 10, and 30 mg CdCl2/kg soil), with or without exogenous proline (20 mM) added to the irrigation water. Different levels of cadmium stress altered plant growth, gas exchange, chlorophyll content, and water status, but to varying degrees. Conversely, cadmium-treated plants showed increased antioxidant enzyme activity, along with higher levels of proline, hydrogen peroxide (H₂O₂), thiobarbituric acid reactants (TBARS), and electrolyte leakage (EL). Interestingly, exogenous proline mitigated the adverse effects of cadmium on young date palms. In fact, it alleviated oxidative damage caused by cadmium accumulation and improved plant growth, water status, and photosynthetic activity. Furthermore, compared to cadmium-treated plants, proline-treated plants exhibited higher activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in their roots and leaves. This study also included hydroponic experiments to investigate the effect of exogenous proline application (Pro; 25 μM) on alleviating arsenate (As(V); 5 and 25 μM) toxicity in eggplant seedlings. Exposure to pentavalent arsenic (As(V)) inhibits eggplant growth and is accompanied by increased arsenic accumulation. However, exogenous application of proline (Pro) can alleviate the toxicity of As(V) in eggplant seedlings by reducing arsenic accumulation. Fluorescence properties (JIP test): phiP0, psi0, phiE0, PIABS, ABS/RC, TR0/RC, ETO/RC, DI0/RC, NPQ, and qP are also affected by As(V). However, the effects of As(V) on PIABS, DI0/RC, and NPQ are more significant. In Pro-treated seedlings, parameters such as phiP0, psi0, phiE0, and PIABS are stimulated, while energy flux parameters (ABS/RC, TR0/RC, ETO/RC, and DI0/RC) are inhibited. Exogenous application of Pro can mitigate the toxic effects of As(V) on photosystem II (PS II) photochemistry. Oxidative stress markers—superoxide radicals, hydrogen peroxide, and malondialdehyde (lipid peroxidation)—were elevated under pentavalent arsenic (As(V)) exposure, but their levels were significantly reduced by exogenous application of proline (Pro). As(V) treatment stimulated the activities of superoxide dismutase, peroxidase, and catalase, but glutathione S-transferase activity was unaffected. Exogenous application of Pro increased the activity of enzymatic antioxidants. Seedlings in both the As(V) and Pro treatment groups showed higher levels of endogenous Pro. The activity of δ1-pyrroline-5-carboxylic acid synthase, a key enzyme in Pro biosynthesis, was higher in the Pro treatment group. As(V) stress inhibited the activity of Pro dehydrogenase, with the lowest activity observed under the Pro+As(V) combination treatment. These results suggest that proline metabolism may play a crucial role in regulating arsenic accumulation and antioxidant levels, and that both treatments together promote eggplant seedling growth compared to treatment with pentavalent arsenic (As(V)) alone. This study aimed to evaluate the protective and therapeutic effects of a specific mixture (containing vitamin C, lysine, proline, epigallocatechin gallate, and zinc) and α-1-antitrypsin on benzo[a]pyrene [B(a)P]-induced lung tumors in mice. Swiss albino mice were divided into two main experimental groups: experimental group (1) mice were injected with 100 mg/kg B(a)P for 28 weeks; experimental group (2) mice were injected with 50 mg/kg B(a)P eight times for 16 weeks. Experiments 1 and 2 were divided into five groups: group I received the excipient, group II received the protective agent mixture, group III received the carcinogen benzo[a]pyrene (B(a)P), group IV received both the protective agent and the carcinogen, and group V received the carcinogen first and then the protective agent. In both experiments, compared with the control group, group III showed significantly increased levels of total sialic acid, thiobarbituric acid reactants, vascular endothelial growth factor, hydroxyproline, and elastase and gelatinase activities (P < 0.001). These changes in biochemical parameters were correlated with histopathological changes. In both experiments, compared with group III, groups IV and V showed significantly reduced levels of the above parameters and improved histopathological changes after receiving the protective agent (P < 0.001). This protective mixture inhibited benzo[a]pyrene-induced tumorigenesis in mouse lung cancer and restored biochemical and histopathological parameters to normal. Furthermore, this mixture is more protective than therapeutic. For more complete data on interactions of (L)-proline (8 in total), please visit the HSDB record page. Non-human toxicity values: Oral LD50 in rats >5110 mg/kg body weight

L-proline is a pyrrolidine whose proline -S hydrogen at the 2-position is replaced by a carboxylic acid group. Among the 20 DNA-encoded amino acids, L-proline is the only one with a secondary amino group at the α-position of its carboxyl group. It is an important component of collagen and is crucial for the normal function of joints and tendons. It also helps maintain and strengthen the heart muscle. L-proline is a micronutrient, nutritional supplement, algal metabolite, Saccharomyces cerevisiae metabolite, Escherichia coli metabolite, mouse metabolite, and a compatibility osmotic regulator. It belongs to the glutamine family of amino acids, protein-forming amino acids, proline, and L-α-amino acids. It is the conjugate base of L-proline salt. It is the conjugate acid of L-proline salt. It is the enantiomer of D-proline. It is the tautomer of L-proline zwitterion. Proline is one of the twenty amino acids that make up proteins in organisms. Proline is sometimes called an imine, although the IUPAC definition of an imine requires the presence of a carbon-nitrogen double bond. Proline is a non-essential amino acid synthesized from glutamate. It is an important component of collagen and is essential for the normal function of joints and tendons. L-proline is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). Proline has also been reported in Angelica sinensis, microalgae, and other organisms with relevant data. Proline is a cyclic non-essential amino acid (actually an imino acid) synthesized in the human body from glutamate and other amino acids, and is a component of many proteins. Proline is abundant in collagen, making up almost one-third of its amino acid residues. Collagen is the main supporting protein of skin, tendons, bones, and connective tissue, promoting their health and healing. (NCI04) L-proline is one of the twenty amino acids that make up proteins in living organisms. Proline is sometimes called an imino acid, but according to the International Union of Pure and Applied Chemistry (IUPAC), imines require a carbon-nitrogen double bond. Proline is a non-essential amino acid synthesized from glutamate. It is an important component of collagen and is essential for the normal function of joints and tendons. L-proline is a non-essential amino acid synthesized from glutamate. It is an important component of collagen and is essential for the normal function of joints and tendons.

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Pharmacological Indications
L-proline is extremely important for the normal function of joints and tendons and also helps maintain and strengthen the myocardium.

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Mechanism of Action
In the kidneys, L-proline oxidase opens its ring and oxidizes it to produce L-glutamate, thereby playing a role in glycogenogenesis. L-ornithine and L-glutamate are converted to L-proline via L-glutamate-γ-semialdehyde. It is abundant in collagen and closely related to the function of joints and tendons.

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Therapeutic Uses
/EXPL THER/ This study aimed to evaluate the protective and therapeutic effects of a specific mixture (containing vitamin C, lysine, proline, epigallocatechin gallate, and zinc) and α-1-antitrypsin on benzo[a]pyrene[B(a)P]-induced lung tumorigenesis in mice. Swiss albino mice were divided into two main experimental groups: experimental group (1) was injected with 100 mg/kg B(a)P for 28 weeks; experimental group (2) was injected with 50 mg/kg B(a)P eight times for 16 weeks. Experiments 1 and 2 were further divided into five groups: Group I received the excipient, Group II received a mixture of protective agents, Group III received the carcinogen benzo[a]pyrene (B(a)P), Group IV received both the protective agent and the carcinogen, and Group V received the carcinogen first and then the protective agent. In both experiments, compared with the control group, Group III showed significantly increased levels of total sialic acid, thiobarbituric acid reactants, vascular endothelial growth factor, hydroxyproline, and elastase and gelatinase activities (P < 0.001). These changes in biochemical indicators were correlated with histopathological changes. In both experiments, compared with Group III, Groups IV and V showed significantly reduced levels of these indicators and improved histopathological changes after receiving the protective agent (P < 0.001). This protective blend inhibits benzo[a]pyrene-induced lung cancer tumorigenesis in mice and restores biochemical and histopathological parameters to normal. Furthermore, this blend focuses more on protective than therapeutic effects.

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Pharmacodynamics
L-proline is a major amino acid in cartilage and is essential for maintaining youthful skin and repairing muscle, connective tissue, and skin damage. It is also crucial for the immune system and the necessary balance in this formulation. It is an important component of collagen and essential for the normal function of joints and tendons. L-proline is extremely important for the normal function of joints and tendons. It helps maintain and strengthen the myocardium.

C5H9NO2

115.1305

115.063

147-85-3

25191-13-3

145742

Flat needles from alcohol + ether; prisms from water
White crystals or crystalline powder

1.2±0.1 g/cm3

252.2±33.0 °C at 760 mmHg

228 °C (dec.)(lit.)

106.3±25.4 °C

0.0±1.1 mmHg at 25°C

1.487

-0.57

2

3

1

8

103

1

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

ONIBWKKTOPOVIA-BYPYZUCNSA-N

InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1

(2S)-pyrrolidine-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~50 mg/mL (~434.29 mM)

Solubility in Formulation 1: 100 mg/mL (868.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)