Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].

Absorption, Distribution and Excretion
Absorbed into intestinal cells via active transport from the small intestinal lumen. ...Rats were fed a diet containing [(14)C-methyl]1-methionine...with 6% sodium formate added, and the amount of [(14)C] converted to [(14)C]formate (in the form of (14)CO2) in urine and exhaled air was measured...The proportion of [(14)C-methyl] in methionine completely oxidized to CO2 was 60-87%... Although free amino acids dissolved in body fluids constitute only a small portion of the total amino acids in the body, they are crucial for the nutritional and metabolic regulation of proteins. ...While plasma is the easiest to sample, most amino acids are found in higher concentrations in the intracellular pools of tissue cells. Typically, large neutral amino acids, such as leucine and phenylalanine, are in near-equilibrium with their plasma concentrations. Other amino acids, particularly glutamine, glutamic acid, and glycine, are 10 to 50 times higher in the intracellular pools than in plasma. Dietary changes or pathological conditions can lead to significant alterations in the concentrations of various free amino acids in plasma and tissue pools. /Amino Acids/
After ingestion, proteins denature under the influence of gastric acid and are hydrolyzed into smaller peptides by pepsin. The activity of pepsin increases with the increase in gastric acid after eating. These proteins and peptides then enter the small intestine, where peptide bonds are hydrolyzed by various enzymes. These specific peptide-hydrolyzing enzymes originate from the pancreas and include trypsin, chymotrypsin, elastase, and carboxypeptidase. The resulting mixture of free amino acids and small peptides is then transported to mucosal cells via various carrier systems, each targeting specific amino acids, dipeptides, and tripeptides, with each system targeting only a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are subsequently secreted into the portal vein bloodstream via other specific carrier systems within the mucosal cells, or further metabolized intracellularly. The absorbed amino acids enter the liver, where some are absorbed and utilized; the remainder enters the systemic circulation and is utilized by peripheral tissues. Even under protein-free feeding conditions, protein continues to be secreted into the gut, and fecal nitrogen loss (i.e., nitrogen lost in feces as bacteria) may account for up to 25% of essential nitrogen loss. Under these dietary conditions, amino acids secreted into the gut as components of proteolytic enzymes and amino acids from shed mucosal cells are the only amino acid sources for maintaining gut bacterial biomass. …Other pathways of loss of complete amino acids include urinary excretion and shedding of skin and hair. These losses are smaller compared to the pathways mentioned above, but can still significantly affect the estimation of requirements, especially in disease states. /Amino Acids/
For more data on the absorption, distribution, and excretion (complete) of (L)-methionine (11 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic
Product of oxidative deamination or transamination—α-keto-γ-methionine butyrate. /Excerpt from Table/
...The oxidation of the methyl group of methionine (S-methyl-L-cysteine and sarcosine) in vivo mainly occurs via the free formic acid pathway, while tetrahydrofolate may not catalyze this formic acid conversion.
...Methionine...is catabolized largely independently of its initial activation to S-adenosyl-L-methionine. This catabolistic system...appears to be similar to the system that catalyzes the oxidation of the methyl group of S-methyl-L-cysteine...The methyl group of methionine...has been shown...to generate formic acid both in vitro and in vivo.
Infants metabolize methionine faster than adults.
For more complete data on the metabolism/metabolites of (L)-methionine (7 in total), please visit the HSDB record page.
Liver

Toxicity Summary
The mechanism by which L-methionine may possess hepatotoxicity resistance is not fully understood. It is believed that the metabolism of high doses of acetaminophen in the liver leads to decreased hepatic glutathione levels and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may possess antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. The antioxidant activity of L-methionine and its metabolites appears to be the reason for its potential hepatotoxicity resistance. Recent studies have shown that methionine itself possesses free radical scavenging activity, thanks to its sulfur atom and chelating ability. Interactions Supplementation with glycine or serine can alleviate the adverse effects of methionine… Vitamin B6 deficiency reduces tolerance to methionine in rats. Pretreatment of juvenile male rats with excessive retinol (800 IU/g diet for 10 days) can partially offset the adverse effects caused by high methionine intake. Adding methionine to the drinking water of pregnant rats injected with sodium valproate reduced embryo reabsorption but did not improve embryonic growth. The serum free methionine level in rats drinking water supplemented with methionine was approximately twice that of the control group, while their water intake was only half that of the control group. Using whole rat embryo culture, simultaneous addition of methionine and sodium valproate to the culture medium did not protect embryos from the teratogenic effects of sodium valproate… however, methionine did protect embryos from the teratogenic effects of sodium valproate, especially when the cultured embryos were taken from pregnant rats that had ingested methionine; this protective effect was more significant. This study demonstrates that short-term vitamin supplementation (folic acid, vitamin B6, and B12) can effectively reduce homocysteine levels after methionine loading, thereby improving endothelial-dependent flow-mediated vasodilation in 16 healthy adults. Following methionine loading, homocysteine levels decreased from 22.7 ± 3.8 μmol/L to 17.0 ± 2.1 μmol/L (p < 0.001), while flow-mediated vasodilation increased from 8.6 ± 3.6% to 13.8 ± 2.9% (p < 0.001). For more complete data on interactions with (L)-methionine (18 in total), please visit the HSDB record page. Non-human toxicity values: Oral LD50 in rats: 36,000 mg/kg; Intraperitoneal LD50 in rats: 4238 mg/kg

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

Therapeutic Uses
Methionine is a sulfur-containing essential amino acid crucial for many bodily functions. It is a heavy metal chelator. Methionine…enhances glutathione synthesis and can be used as an alternative to acetylcysteine in the treatment of acetaminophen poisoning. Many symptoms of selenium poisoning can be prevented by a high-protein diet and by taking methionine in the presence of vitamin E. In Europe, oral methionine (10 grams over 12 hours) has been approved for replenishing depleted glutathione reserves and preventing hepatotoxicity following high doses of acetaminophen. In the United States, Canada, Scotland, and most of England, N-acetyl-L-cysteine remains the antidote of choice for acetaminophen overdose. For more complete data on the therapeutic uses of (L)-methionine (9 types), please visit the HSDB records page. Drug Warnings Methionine may cause nausea, vomiting, drowsiness, and irritability. It should not be used in patients with acidosis. Methionine may exacerbate hepatic encephalopathy in patients with confirmed liver damage; caution should be exercised when using it in patients with severe liver disease. Vomiting is a common adverse reaction. Methionine…taking it more than 10 hours after ingestion may exacerbate hepatic encephalopathy. This article reports a case of death in a control subject after oral administration of a large dose of methionine. This study aimed to explore the possible relationship between homocysteine and Alzheimer's disease. The subject's plasma methionine concentration after oral administration was significantly higher than previously reported concentrations in humans taking the standard oral dose of methionine (100 mg/kg body weight). Pre-administration plasma metabolite values ruled out known genetic disorders that could cause abnormally high methionine concentrations. The most likely explanation is that the subject ingested an excessive amount of methionine. This article explores the possibility that extremely high concentrations of methionine may lead to severe brain damage and recommends against increasing the dose of methionine to improve the sensitivity of standard methionine loading tests, or if attempted, with extreme caution.
In studying the genetic factors of atherosclerosis, the authors documented acute complications during a standard methionine loading test (dose of 100 mg/kg body weight) and assessed 30-day mortality in 296 patients with coronary or peripheral artery disease and 591 controls. Acute complications were observed in 33% of women and 16.5% of men. The incidence of complications was the same in both sexes. The most common symptom was dizziness, attributed to the methionine loading. In addition, some subjects also observed drowsiness, nausea, polyuria, and a decrease or increase in blood pressure. Within 30 days after the test, none of the 887 subjects died…
Pharmacodynamics
L-methionine is a major source of sulfur and can prevent hair, skin, and nail diseases; help lower cholesterol levels by increasing the production of lecithin in the liver; reduce liver fat and protect the kidneys; is a natural chelator of heavy metals; regulates ammonia production and produces ammonia-free urine, thereby reducing bladder irritation; affects hair follicles and promotes hair growth. L-methionine may help counteract the toxic effects of hepatotoxic toxins such as acetaminophen. Methionine may also possess antioxidant activity.

C5H11NO2S

151.114206552505

151.046

1006386-95-3

26062-47-5

6137

White to off-white solid powder

1.2±0.1 g/cm3

536 to 540 °F decomposes 541.4-543.2 °F (NTP, 1992)

1.531

-1.9

2

4

4

9

97

1

CSCC[C@@H](C(=O)O)N

FFEARJCKVFRZRR-BYPYZUCNSA-N

InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1

(2S)-2-amino-4-methylsulfanylbutanoic 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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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