l-Methionine

149.21100

149.21

200-562-9

AE28F7PNPL

760117

DTXSID5040548

C29600

Minute hexagonal plates from dilute alcohol|Colorless or white, lustrous plates or as white, crystalline powder

V - Various

2930400000

88.62000

-1.9

Minute hexagonal plates from dilute alcohol. (NTP, 1992)

1.206 g/cm3

280-282 °C (decomp)

123-126 °C @ Press: 15 Torr

139.4ºC

1.531

H2O: soluble

Store at RT.

8.14X10-8 mm Hg at 25 deg C (est)

LD50 oral in rat: 36gm/kg

Specific optical rotation: 22.5 deg at 25 °C/D (1 N HCl)

Faint

Sulfurous

pH (1% aqueous solution) = 5.6-6.1

2.28(at 25 °C)

Henry's Law constant = 2.11X10-11 atm-cu m/mol at 25 °C (est)

2.28 (at 25 °C)|pKa = 2.28; pK2 = 9.21

133.65 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]|152.05 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|127 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]|133.1 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|132 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|134.08 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]|140.5 Ų [M-H]-

Platelets from alcohol. mp 281 °C (decomposes), density 1.340; pKa1 = 2.28, pKa2 = 9.21; pH of 1% aqueous solution 5.6-6.1; Rf value 0.77. Solubility in water (g/L) at 0 °C: 18.18; at 25 °C: 33.81; at 50 °C: 60/.70; at 75 °C: 15.2 °C. Soluble in dilute acids, alkalies. Very slightly soluble in 95% alcohol. Insoluble in ether. /Methionine, DL-form/|UV: 1-65 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Methionine (DL)/|Hydroxyl radical reaction rate constant = 5.13X10-11 cu cm/molec-sec at 25 °C (est)

Reacts with water, steam, and/or acids to produce toxic and flammable vapors of hydrogen sulfide (NTP, 1992). Water soluble (NTP, 1992). pH of 1% aqueous solution is 5.6-6.0.

Sulfides, Organic

An organosulfide and amine derivative, carboxylic acid. Look at Reactive Groups 20 (organosulfides), 7 (amines), and 3 (carboxylic acids) may give indications about reactive tendencies. It is an amino acid essential in human nutrition.

NONH for all modes of transport

2

R33

S24/25

PD0457000

F

Stable. Incompatible with strong oxidizing agents.

P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.|SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

L-Methionine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.|Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: methionine is included in weight control drug products.|Methionine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.

NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2009).[Available from, as of March 10, 2010: http://www.nap.edu/catalog/10490.html]

Flash point data for this material is not available, but it is probably combustible. (NTP, 1992)

Not Classified

Fires involving this material can be controlled using a CO2, foam, and/or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should keep this material in a tightly-closed container under an inert atmosphere, and store it at refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

SOIL: (L)-Methionine concentrations in three soil horizons of an active landfill, the Conica Montemarte outside of Seville, Spain, were reported as 0.5 nmol/g (1.0-1.5 meters), 19.9 nmol/g (3.0-3.5 meters), and 38.2 nmol/g (6.5-7.0 meters), 6, 18, and 24 months after deposition respectively(1).|SEDIMENT: (L)-Methionine concentrations of 0.46 to 0.055 umol/g were detected in carbonate sediment samples collected from a lagoon of Fanning Island, an atoll in the Line Islands of the Central Pacific Ocean(1).

Doses of L-methionine of up to 250 mg daily are generally well tolerated. Higher doses may cause nausea, vomiting and headache. Healthy adults taking 8 grams of L-methionine daily for four days were found to have reduced serum folate levels and leucocytosis. Healthy adults taking 13.9 grams of L-methionine daily for five days were found to have changes in serum pH and potassium and increased urinary calcium excretion. Schizophrenic patients given 10 to 20 grams of L-methionine daily for two weeks developed functional psychoses. Single doses of 8 grams precipitated encephalopathy in patients with cirrhosis.

The adverse effects of methionine are alleviated by supplements of glycine or serine ... Vit B6 deficiency reduces the tolerance of the rat for methionine.|Pretreatment of young male rats with excess retinol (800 IU/g diet for 10 days) partially counteracted the adverse effects caused by a high methionine intake.|Methionine provided in the drinking water of pregnant rats injected with sodium valproate reduced the frequency of resorptions but did not improve embryo growth. Rats drinking methionine supplemented water had approx twice the level of serum free methionine and consumed only one half the volume of water as controls. Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from the teratogenic effects of sodium valproate ... Protection from the teratogenic effects of sodium valproate was afforded by methionine and was particularly striking when embryos for culture were taken from pregnant rats that had been consuming methionine.|This study showed that short-term vitamin administration /(folic acid, vitamins B6 and B12)/ effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.|For more Interactions (Complete) data for (L)-Methionine (18 total), please visit the HSDB record page.

LD50 Rat oral 36,000 mg/kg|LD50 Rat ip 4238 mg/kg

This case-controlled, monocenter association study included 290 patients of Caucasian origin undergoing surgical resection for intracranial meningioma (World Health Organization [WHO] Grade I, 190 cases; WHO Grade II, 82 cases; WHO Grade III, 18 cases) and 287 age- and sex-matched local controls. The authors analyzed the following genetic variants: dihydrofolate reductase c.594+59del19, 5,10-methylenetetrahydrofolate reductase c.677C > T and c.1298A > C, 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR) c.2756A > G, reduced folate carrier 1 c.80G > A, cystathionine beta-synthase (CBS) c.844_855ins68 and transcobalamin 2 c.776C > G. RESULTS: The variant CBS c.844_855ins68 -- that is, the allele carrying the insertion ("ins" or "i") as opposed to the wild-type allele designated as deletion ("del" or "d") -- was significantly overrepresented in meningioma patients (dd/ id/ii: 0.81/0.18/0.01) in comparison with the controls (dd/id/ii: 0.88/0.12/0; 2 df, chi-square 8.97, p = 0.011; multiple nominal regression with age and sex as covariables). In addition, explorative analyses revealed an association of the MTR c.2756A > G variant with meningioma WHO Grade III (AA/AG/GG: patients, 1.0/0/0; controls, 0.64/0.32/0.04; 2 df, chi-square 14.44, p = 0.001). CONCLUSIONS: The results of this study suggest that genetic variants of methionine metabolism are associated with meningioma formation.

(L)-Methionine is formed in natural waters through metabolism of naturally occurring proteins(1). It is one of the nine indispensable amino acids that cannot be synthesized to meet body needs in animals and therefore must be provided in the diet(2). (L)-Methionine is a naturally occurring amino acid constituent of egg albumin, casein, and beta-lactoglobulin proteins(3); (L)-methionine occurs naturally in foods such as maize, rice, wheat, potato, soybeans, lettuce, bean, tomato, apples, oranges, beef, veal, fish, milk, cheese and eggs(3).

(L)-Methionine's production and use as nutritional supplement in animal feeds(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -1.87(2) and a regression-derived equation(3), indicates that (L)-methionine is expected to have very high mobility in soil(SRC). The pKa values of (L)-methionine are 2.28 and 9.21(4), indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC). Volatilization from moist soil is not expected because ions do not volatilize(SRC). (L)-Methionine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Using a laboratory activated sludge system, (L)-methionine exhibited an 80% theoretical BOD reduction in 16 days, producing 3-mercaptopropionate, methanethiol and dimethylsulfide(6); this suggests that biodegradation may be an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -1.87(2) and a regression-derived equation(3), indicates that (L)-methionine is not expected to adsorb to suspended solids and sediment(SRC). The pKa values of 2.28 and 9.21(4) indicates (L)-methionine will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using a laboratory activated sludge system, (L)-methionine exhibited an 80% theoretical BOD reduction in 16 days, producing 3-mercaptopropionate, methanethiol and dimethylsulfide(8); this suggests that biodegradation may be an important environmental fate process in water(SRC).|AQUATIC FATE: (L)-Methionine has been shown to degrade in sunlit natural water through a photo-sensitized oxidation involving singlet oxygen(1,2); assuming that the top meter of sunlit natural water has a singlet oxygen concn of 4X10-14 M, the photooxidation half-life for the reaction (L)-methionine with singlet oxygen has been estimated to be about 200 hr at pH 6-11(1); the near-surface photooxidation rate (via singlet oxygen) of (L)-methionine in Okefenokee Swamp water from Georgia is predicted to be about 3 hr(2). Bioconcentration and volatilization are not expected to important fate processes because of its high water solubility(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), (L)-methionine, which has an estimated vapor pressure of 8.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase (L)-methionine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7.5 hours(SRC), calculated from its rate constant of 5.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). (L)-Methionine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of (L)-methionine with photochemically-produced hydroxyl radicals has been estimated as 6.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). (L)-Methionine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). (L)-Methionine does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for (L)-methionine(SRC), using a log Kow of -1.87(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of (L)-methionine is estimated as 8(SRC), using a log Kow of -1.87(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that (L)-methionine is expected to have very mobility in soil. The pKa values of (L)-methionine are 2.28 and 9.21(4), indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC). One study found that (L)-methionine was one of many amino acids that sorbed to carbonate sediments in seawater(5); a positive correlation between surface area (of the sediment) and the amount of sorbed amino acids indicated that sorption from solution (partitioning from the water column to sediment) was a likely mechanism(5).

The pKa values of 2.28 and 9.21(1) indicate (L)-methionine will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). (L)-Methionine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.1X10-8 mm Hg(SRC), determined from a fragment constant method(3).

The average methionine content of some foodstuffs (in mg/100g) has been reported as follows: maize, grain: 182; rice, husked: 183; wheat, whole grain: 196; potato: 26; bean (Phaselous vulgaris): 234; soybean, milk: 50; soy protein, isolate: 1008; tomato: 7; apple: 3; orange: 12; beef, veal, edible flesh: 478; fish: 220; cheese: 530; egg, whole: 416(1).

ENVIRONMENTAL: The average (L)-methionine content of cows milk is reported as 86 mg/100 g(1). The average (L)-methionine content of human milk is reported as 19 mg/100 g(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 28,250 workers (17,038 of these were female) were potentially exposed to (L)-methionine in the US(1). Occupational exposure to (L)-methionine may occur through inhalation and dermal contact with this compound at workplaces where (L)-methionine is produced or used. Monitoring and use data indicate that the general population may be exposed to (L)-methionine via ingestion of food or other consumer products containing (L)-methionine(SRC).

The average (L)-methionine content of human milk is reported as 19 mg/100 g(1).

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.|Parenteral nutrition

A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals|Methionine ... enhances the synthesis of glutathione and is used as an alternative to acetylcysteine in the treatment of paracetamol poisoning.|... Many of signs of toxicity /of selenium poisoning/ can be prevented by high-protein diets, and by methionine in the presence of Vitamin E.|In Europe, oral methionine (10 g over 12 hours) is approved as an agent to restore depleted glutathione stores and prevent hepatotoxicity after large acetaminophen ingestions. N-Acetyl-L-cysteine remains the preferred antidote for acetaminophen overdose in the United States, Canada, Scotland, and most of England.|For more Therapeutic Uses (Complete) data for (L)-Methionine (9 total), please visit the HSDB record page.

Methionine may cause nausea, vomiting, drowsiness, and irritability. It should not be used in patients with acidosis. Methionine may aggravate hepatic encephalopathy in patients with established liver damage; it should be used with caution in patients with severe liver disease.|Vomiting is a common adverse effect.|Methionine ... may exacerbate hepatic encephalopathy when administered more than 10 hours postingestion.|The death of a control subject after an oral load of methionine for a study of the possible relationship between homocysteine and Alzheimer's disease is reported. The subject developed postload plasma concentrations of methionine far beyond those reported previously in humans given the usual oral loading dose of methionine (100 mg/kg body wt). Her preload plasma metabolite values rule out known genetic diseases that might predispose one to unusually high methionine concentrations. The most likely explanation for these events is that the subject received a substantial overdose of methionine. The possibility that extremely high methionine concentrations may lead to severe cerebral effects is discussed, and it is recommended that any move to increase the sensitivity of the usual methionine loading test by increasing the dose of methionine either not be undertaken or be taken only with extreme care.|When studying genetic factors in arteriosclerosis /the authors/ recorded acute complications during a standard methionine loading test (with a dose of 100 mg/kg bw) and assessed a 30-day mortality in a group of 296 patients with coronary artery or peripheral arterial disease and in 591 controls. Acute complications were observed in 33% of the women and 16.5% of the men. For each sex, the patients and controls exhibited the same proportion of complications. The most common symptom, dizziness, was attributable to methionine loading. In addition, isolated sleepiness, nausea, polyuria and decreased or increased blood pressure were observed in part of the subjects. None of the 887 individuals died within the 30-day period following the test...

L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.|... Rats were fed diets containing [(14)C-methyl]l-methionine ... with 6% of sodium formate, and conversion of (14)C into [(14)C]formate was measured in urine and exhaled air (as (14)CO2) ... Total oxidation of [(14)C-methyl] into CO2, amounted to 60-87% for methionine ...|Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/|After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/|Protein secretion into the intestine continues even under conditions of protein-free feeding, and fecal nitrogen losses (ie, nitrogen lost as bacteria in the feces) may account for 25% of the obligatory loss of nitrogen. Under this dietary circumstance, the amino acids secreted into the intestine as components of proteolytic enzymes and from sloughed mucosal cells are the only sources of amino acids for the maintenance of the intestinal bacterial biomass. ... Other routes of loss of intact amino acids are via the urine and through skin and hair loss. These losses are small by comparison with those described above, but nonetheless may have a significant impact on estimates of requirements, especially in disease states. /Amino acids/|For more Absorption, Distribution and Excretion (Complete) data for (L)-Methionine (11 total), please visit the HSDB record page.

Hepatic|Product of oxidative deamination or transamination--alpha-keto-gamma-methiolbutyric acid. /From table/|... Oxidation of methionine (S-methyl-l-cysteine and sarcosine) methyl group in vivo proceeds primarily by way of free formate, and that conversion to formate is probably not catalysed by tetrahydrofolic acid.|... Methionine ... is catabolized to a large extent independently of initial activation to S-adenosyl-l-methionine. The system for catabolism ... appears analogous to one that catalyses oxidation of S-methyl-l-cysteine methyl group ... The methyl group of methionine ... /has been/ shown ... to yield formate in vitro and in vivo.|Infants more rapidly metabolized methionine than adults.|For more Metabolism/Metabolites (Complete) data for (L)-Methionine (7 total), please visit the HSDB record page.

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.|Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Protein synthesis/|The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Protein degradation/|Methionine dependence, the inability of cells to grow when the amino acid methionine is replaced in culture medium by its metabolic precursor homocysteine, is characteristic of many cancer cell lines and some tumors in situ. Most cell lines proliferate normally under these conditions. The methionine dependent tumorigenic human melanoma cell line MeWo-LC1 was derived from the methionine independent non-tumorigenic line, MeWo. MeWo-LC1 has a cellular phenotype identical to that of cells from patients with the cblC inborn error of cobalamin metabolism, with decreased synthesis of cobalamin coenzymes and decreased activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. Inability of cblC cells to complement the defect in MeWo-LC1 suggested that it was caused by decreased activity of the MMACHC gene. However, no potentially disease causing mutations were detected in the coding sequence of MMACHC in MeWo-LC1. No MMACHC expression was detected in MeWo-LC1 by quantitative or non-quantitative PCR. There was virtually complete methylation of a CpG island at the 5'-end of the MMACHC gene in MeWo-LC1, consistent with inactivation of the gene by methylation. The CpG island was partially methylated (30-45%) in MeWo and only lightly methylated (2-11%) in control fibroblasts. Infection of MeWo-LC1 with wild type MMACHC resulted in correction of the defect in cobalamin metabolism and restoration of the ability of cells to grow in medium containing homocysteine. /It was concluded/ that epigenetic inactivation of the MMACHC gene is responsible for methionine dependence in MeWo-LC1.

ACUTE/CHRONIC HAZARDS: This material is dangerous when heated to decomposition; it emits dangerous and highly toxic fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ Methionine was administered to 17 adults with liver disease 8-20 g/day in divided doses for 3-9 days. In 7 patients with portal cirrhosis, neurological deterioration occurred from 1-4 days after total doses of 11-46 g. Methionine was tolerated in 10 controls.|/HUMAN EXPOSURE STUDIES/ Oral methionine supplements (8.0 g daily for 4 days) were given to five normal volunteers who continued to eat their usual diet. This treatment resulted in a significant fall in serum folate concentration. Three days after the end of treatment concentrations had not completely returned to control values. The fall in concentration was prevented by giving oral folic acid supplements.|/HUMAN EXPOSURE STUDIES/ ... The aim of the study was to investigate if methionine supplementation causes changes in endothelial function, plasma homocysteine, or lipid peroxidation which may be associated with atherosclerosis. Sixteen healthy volunteers were studied. Forearm blood flow in response to local intra-arterial infusion of acetylcholine to assess endothelium-dependent vasodilatation and sodium nitroprusside to assess endothelium-independent vasodilatation was measured by venous occlusion plethysmography. Plasma homocysteine and lipid peroxidation, measured as thiobarbituric acid reactive substances, were measured using high-performance liquid chromatography. Forearm vascular responses, plasma homocysteine concentrations, and thiobarbituric acid reactive substances were measured at baseline and following methionine supplementation. RESULTS: There was no significant difference in endothelial-dependent vascular responses after acute (methionine 250 mg orally, p > 0.05), 1 month of low-dose (methionine 250 mg daily, p > 0.05), or 1 week of high-dose (methionine 100 mg/kg daily, p > 0.05) methionine administration. There was no significant difference in plasma homocysteine concentrations after acute (p > 0.05) or 1 month of low-dose (p > 0.05) methionine administration. However, 1 week of high-dose methionine (100 mg/kg) administration daily significantly increased homocysteine concentrations (p < 0.0015). Thiobarbituric acid reactive substances were unchanged during the period of study (p > 0.05)...|/HUMAN EXPOSURE STUDIES/ Prolonged exposure to nitrous oxide causes adverse effects mimicking those of cobalamin deficiency. This is explained by irreversible oxidation of cobalamin bound to the enzyme methionine synthase. The inactivation of methionine synthase by nitrous oxide in cultured human fibroblasts is decreased at high concentrations of methionine in culture medium. ... The possible protection against cobalamin inactivation by preoperative methionine loading /was investigated/ in patients undergoing nitrous oxide anesthesia. Fourteen patients receiving anesthesia for 75-230 min were included. Half of these patients received a peroral methionine loading dose 2 hr before anesthesia. After nitrous oxide exposure, a considerable inactivation of methionine synthase in mononuclear white blood cells was seen in all patients, reaching a nadir after 5-48 hr. In the patients not subjected to a methionine load, recovery of enzyme activity was not complete within 7 days. In the patients receiving a methionine load, the kinetics of inactivation of methionine synthase were similar, but the rate and extent of enzyme recovery was higher than in patients not receiving methionine, and in four patients, the enzyme activity even exceeded the preoperative level. The inactivation of methionine synthase was associated with a transient increase in plasma homocysteine, and the homocysteine concentration was still increased (mean 28.7%) 7 days after anesthesia in the patients not receiving methionine. A marked peak in homocysteine concentration was observed immediately after anesthesia in the methionine-loaded patients, but the homocysteine level was still increased (mean of 30.5%) after 7 days. The activity of the other cobalamin-dependent enzyme, methylmalonyl coenzyme A mutase, in the mononuclear white blood cells, and the serum concentration of the cobalamin marker methylmalonic acid, were not altered after nitrous oxide anesthesia or methionine loading or both...|For more Human Toxicity Excerpts (Complete) data for (L)-Methionine (19 total), please visit the HSDB record page.

L-Isomer Methionine

Used almost exclusively to improve the nutritive value of animal feeds /DL-Methionine/

NF, feed 98%|USP and FCC grades; 99% feed grade|Racemate mixture of D- and L- methionine

L-Methionine: ACTIVE|... Available as d,l-methionine and as calcium salt of hydroxy analog of methionine. These products are used ... in animal feeds ... Relative biological value of these compared to l-methionine ... evidence suggests equivalency on mole basis both in rats and man.|The D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is inexpensively produced by the chemical synthesis is primarily used as a feed supplement|The amino acids that are incorporated into mammalian protein are alpha-amino acids, with the exception of proline, which is an alpha-imino acid. This means that they have a carboxyl group, an amino nitrogen group, and a side chain attached to a central alpha-carbon. Functional differences among the amino acids lie in the structure of their side chains. In addition to differences in size, these side groups carry different charges at physiological pH (e.g., nonpolar, uncharged but polar, negatively charged, positively charged); some groups are hydrophobic (e.g., branched chain and aromatic amino acids) and some hydrophilic (most others). These side chains have an important bearing on the ways in which the higher orders of protein structure are stabilized and are intimate parts of many other aspects of protein function.

Method: AOAC 960.47; Procedure: microbiological, turbidimetric and titrimetric methods; Analyte: methionine; Matrix: vitamin preparations; Detection Limit: not provided.|Method: AOAC 994.12; Procedure: performic acid oxidation with acid hydrolysis-sodium metabisulfite method; Analyte: methionine; Matrix: feeds; Detection Limit: not provided.|Method: AOAC 999.13; Procedure: high performance liquid chromatography post-column derivatization; Analyte: methionine; Matrix: feed grade amino acid trade products or in premixes with more than 10% individual amino acid content; Detection Limit: not provided.|SIMPLE PROCEDURE IN WHICH SILVER LIGAND CHROMATOGRAPHY IS USED TO ISOLATE METHIONINE FROM AMINO ACID MIXTURES IS DESCRIBED.|The following methods have been developed for the analysis of free amino acids in blood, food, and feedstocks: (1) Protein hydrolysis, (2) Chromatographic methods that include high performance liquid chromatography (HPLC), gas chromatography (GC) and thin-layer chromatography (TLC), (3) Colorimetric and Fluorimetric Analysis, (4) Spectrometric Analysis, and (5) Enzymatic Determination and Microbial Assay /amino acids/

GC-MS determination in biological fluids

EPA Safer Chemical Functional Use Classes -> Skin Conditioning Agents|Safer Chemical Classes -> Green half-circle - The chemical is expected to be of low concern|Food additives -> Flavoring Agents|Human Drugs -> EU pediatric investigation plans|Cosmetics -> Antistatic; Hair conditioning; Skin conditioning

Flavoring Agents