General Description
Minute hexagonal plates from dilute alcohol.
Reactivity Profile
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. L-METHIONINE(63-68-3) is an amino acid essential in human nutrition.
Air & Water Reactions
Reacts with water, steam, and/or acids to produce toxic and flammable vapors of hydrogen sulfide . Water soluble . pH of 1% aqueous solution is 5.6-6.0.
Health Hazard
ACUTE/CHRONIC HAZARDS: This material is dangerous when heated to decomposition; it emits dangerous and highly toxic fumes.
Fire Hazard
Flash point data for this material is not available, but L-METHIONINE is probably combustible.
Originator
Meonine ,Ives,US,1944
Definition
ChEBI: The L-enantiomer of methionine.
Preparation
The production method of choice for L-methionine is still the enzymatic resolution of racemic N-acetyl-methionine using acylase from Aspergillus oryzae. The production is carried out in a continuously operated fixed-bed or enzyme membrane reactor.
Production Methods
Numerous methods have been described for manufacture of
methionine, including hydrolysis of methionine amide )and 5-(bmethylmercaptoethyl)-
hydantoin.
Manufacturing Process
A 3-necked flask fitted with a stirrer, thermometer, gas inlet, dropping funnel, and brine-cooled reflux condenser was charged with 53 g (1.1 mol) methyl mercaptan and 0.35 g mercuric methyl mercaptide. After admitting 56 g (1.0mol) of acrolein during the course of 15 minutes with an inside temperature of
about 10°C, the temperature was allowed to rise spontaneously to 75°C, at
which point an ice bath was applied. There was no indication of further
reaction one hour after the addition of the acrolein. Distillation of the product
gave 71 g (yield 68%) of β-methylmercaptopropionaldehyde, as described in
US Patent 2,584,496.
Then as described in US Patent 2,732,400, β-methylmercaptopropionaldehyde
(0.60 M) (56.5 g) is added to a stirred solution of sodium cyanide (0.66 M)
(32.4 g) and ammonium chloride (0.63 M) (33.7 g) in water (140 ml). The
temperature of the mixture rises to 49°C and is maintained at this point by
heat evolution for about 5 minutes when it slowly begins to fall. Methanol (50
ml) is added and the mixture is stirred for 4 hours as the temperature falls to
28°C (room temperature).
After chilling to +12°C, additional methanol (35 ml) and a concentrated
aqueous ammoniun hydroxide solution (1.4 M) (100 ml) are added and
stirring is continued for 2 hours at a temperature maintained at from +5° to
+15°C. The organic layer is separated and solvent is stripped from the
aqueous layer at water aspirator pressure at a temperature below 40°C. The
residue is extracted several times with chloroform and the chloroform extracts
are combined with the separated oil. Chloroform is removed at water aspirator
pressure at a temperature below 35°C to leave crude α-amino-γmethylmercaptobutyronitrile (methionine nitrile) in 88% yield (68 g) as a
clear, somewhat viscous oil.
The methionine nitrile (20 g) is dissolved in a solution prepared from 50 ml of
aqueous 5 N sodium hydroxide solution and 65 ml of ethanol. The solution is
then refluxed for 24 hours; ammonia is evolved. The solution is treated with
activated carbon, filtered, acidified with glacial acetic acid (17 ml), chilled to -
10°C and filtered to give crude product. This crude product is then slurried
with a solution made up of 20 ml of water and 20 ml of methanol, filtered at -
5° to +10°C and dried to give dl-methionine as white platelets.
Therapeutic Function
Lipotropic
Pharmaceutical Applications
Methionine is used in oral pharmaceutical formulations as a
flavoring agent.It has been included in parenteral formulations as
a pH controlling agent,and it has also been used experimentally
as an antioxidant with antibodies.Methionine is also used
therapeutically in oral tablets
Biochem/physiol Actions
L-Methionine serves as precursor for transmethylation and transsulphuration. Methionine adenosylation results in the formation of S-adenosyl-L-methionine (SAM). SAM serves as a methyl donor to a number of substances. This methylation is significantly associated with the immune system functioning. Thus, SAM deficiency causes severe combined immunodeficiencies. L-Methionine′s metabolic product, glutathione, is known to regulate immune response and has antiviral action.
Safety
Methionine is used in oral pharmaceutical formulations. The pure
form of methionine is mildly toxic by ingestion and by the IP route.
LD50 (rat, IP): 4.328 g/k
LD50 (rat, oral): 36 g/kg
storage
Methionine is sensitive to light and should be stored in a cool, dark
place.
Purification Methods
Crystallise L-methionine from aqueous EtOH. Also purify it by dissolving ~0.5g of amino acid in ~10mL of hot H2O, filtering, adjusting the pH to 5.8 with 5N HCl, collecting the solid after addition of ~20mL of EtOH. It is recrystallised by dissolving in H2O and adding EtOH. It sublimes at 197-208o/0.3mm with 99.8% recovery and unracemised [Gross & Gradsky J Am Chem Soc 77 1678 1955]. [Milne & Peng J Am Chem Soc 79 647 1957, Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 3 pp 2125-2152 1961, Beilstein 4 IV 3189.]
Incompatibilities
Methionine is incompatible with strong oxidizing agents.
Regulatory Status
Included in the FDA Inactive Ingredients Database (oral tablets).
Included in parenteral preparations (injection solutions; powders
for reconstitution) licensed in the UK.
