Methionine

• (S) - (-) -methionine
• L-methionine
• (R) - ( ) -methionine
• D-methionine
• (±) -methionine
• DL-methionine
• ( RS)- methionine
• 2-amino -4- methylmercaptobutyric acid
• α -amino- γ - methylmercaptobutyric acid
• IUPAC: 2-amino- 4-( methylsulfanyl ) butanoic acid (without stereochemistry)
• Acimetion
• Abbreviations: Met ( Three letter code)
• M ( one-letter code )

• 63-68-3 (L- enantiomer)
• 348-67-4 (D - enantiomer)
• { 59-51-8 DL -methionine [ Synonym: ( ±) -methionine ]}

• V03AB26
• V06DE00

Colorless crystals

Fixed

1.34 g · cm -3

280-281 ° C ( decomposition)

• PKCOOH: 2.28 (25 ° C)
• PKNH2: 9.21 (25 ° C)

Moderately in water: 48 g · l-1 (20 ° C)

36 g · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Methionine is Met or M abbreviated, is an essential proteinogenic, sulfur-containing α - amino acid in its natural L-form.

Properties

In addition to cysteine ​​Methionine is the only sulfur-containing proteinogenic amino acid. The thioether it is less reactive than cysteine ​​, the sulfur atom is part of a thiol group ( mercapto group ). Methionine is present predominantly as an inner salt or zwitterion, whose formation can be explained by the fact that the proton of the carboxyl group migrates to the free electron pair of the nitrogen atom of the amino group:

In an electric field, the zwitterion migrates not because it is not loaded as a whole. Strictly speaking, this is at the isoelectric point (IEP ) of the case, which is methionine, at pH 5.74. At this pH the methionine has its lowest solubility in water.

Methionine metabolism is a supplier of methyl groups (- CH3), for example, the biosynthesis of choline, creatine, adrenaline, carnitine, nucleic acids, histidine, taurine and glutathione ( transmethylation ). The metabolically active form of methionine, S -adenosylmethionine.

• Van der Waals volume: 124
• Hydrophobicity: 1.9

Occurrence

Methionine is found in the proteins of all living beings. Since the human body can not produce this amino acid, it is dependent on the dietary intake. The following examples of the methionine content are each based on 100 g of the food, in addition, the percentage is indicated on the total protein:

All of these foods contain almost exclusively chemically bound L- methionine as protein component, however, no free L-methionine.

Demand

In the body, methionine serves, among other things, for the production of non-essential, sulfur-containing proteinogenic amino acid cysteine ​​also. In the absence of cysteine, in the diet, the average methionine requirement of healthy adults in a daily basis about 13 to 16 mg per kilogram body weight. The daily amount that is sufficient for almost all healthy adults ( RDA) is estimated to be 21 mg per kilogram of body weight. Sometimes, this amount is referred to as the total requirement of sulfur-containing amino acids. ( Correctly, then you have but grams but moles can be selected as the Molar mass of methionine and cysteine ​​differ significantly as a unit no. ) The extent to which cysteine ​​can replace methionine, has not been clarified in humans sufficient and seems very depend on the experimental conditions. The data for the average demand for methionine when the diet contains an excess of cysteine, vary for healthy adults 5-13 mg per kilogram of body weight.

Biochemistry

Functions, recovery

Methionine from humans and many animals not be synthesized, but must be taken with food. As part of the translation, the protein is always started with methionine due to the start codon of the single AUG, which is thus the first amino acid at the N -terminus of the resulting protein in each of all living cells. Later, the first methionine but is often separated or modified, for example by acetylation or formylation (mainly for bacteria ) of the amino group.

Not needed for protein methionine can be implemented by linking ATP to S- adenosylmethionine (SAM ), an important methyl group donor in most organisms. After delivery of the methyl group is formed S- adenosyl homocysteine ​​(SAH ), which finally converted to homocysteine ​​and methionine from which is recovered and thermal again.

SAM and methionine is also thus a starting material for the synthesis of polyamines, however, methionine is recovered from the resulting by-product methylthioadenosine - called the methionine salvage pathway.

Reduction of excess methionine

Methionine is only irreversibly degraded when there is a surplus. In the case of two possible pathways can be activated: on the one hand the conversion to cysteine ​​via SAM and homocysteine ​​- the reduction of excess cysteine ​​to sulfate and taurine has been well studied; on the other hand could also take place via transamination degradation - while the balance is reversed in the last reaction of the methionine salvage pathway and is formed from methionine 5' -methylthio -3- ketobutanoat ( MOB), the use of the enzyme complex Branched - keto acid dehydrogenase is further processed and short- chain acyl -CoA dehydrogenase to Methylthiopropionyl -CoA, from which methanethiol is produced which is partly excreted as CO2 and sulfate and partially used in the liver in THF cycle.

This safety valve for excess sulfur can of course only work up to a certain limit with no side effects. Older studies showed acidosis in weanling rats ( 600 mg methionine / day); hepatic coma in dogs, which is accompanied by increased ammonium value templates; and even death in sheep, large amounts of the racemate were in their gizzard (24 g / day).

Due to the assumption, an increased level of SAM increased rate of DNA methylation could cause investigated Amaral and others, whether rats had elevated methionine (2% in the diet for six weeks ) unstable DNA or methylation of the p53 gene, found However, none of these effects. On the other hand, the diet a decreased level of glutathione in the kidney filled up again, which had previously been caused artificially. This shows that excess methionine initially benefit the Cysteinpool before sulfate is excreted.

Chemical Synthesis

The industrial synthesis of racemic methionine (mixture of 50 % L -methionine and D- methionine) is based on petrochemical raw materials, particularly propylene, sulfur, methane and ammonia. According to current methods as the intermediates acrolein, methyl mercaptan and hydrogen cyanide are presented. The addition of methyl mercaptan to the carbon- carbon double bond of acrolein, then provides the intermediate 3 - methylmercaptopropionaldehyde. Subsequently, this aldehyde is converted into a hydantoin derivative of ammonia, carbon dioxide and hydrogen cyanide, the base hydrolysis leads to alkali metal salt of methionine. By neutralization with an acid ( carbon dioxide or sulfuric acid) is obtained racemic methionine, which are produced annually more than 100,000 tons; World market leader for Evonik Industries. For the resolution of racemic methionine is acetylated on the nitrogen atom. The racemic N-acetyl -methionine is treated with the enzyme L- enantioselective acylase, while the natural L-methionine is formed with elimination of acetic acid / acetate, while the D-form of N-acetyl- methionine remains unchanged. Then L-methionine is separated off. The DN -acetyl -methionine is racemized with acetic anhydride and recycled.

Medical use

In the metabolism of excess methionine, the sulfur contained in the substance is oxidized to sulfuric acid and excreted through the kidneys, causing the urine is acidified. The mechanism of Harnansäuerung can assist in some diseases healing. Therapeutically L-methionine is used for:

• Optimize the effect of antibiotics with optimum activity in the acidic urine (pH 4-6): eg, ampicillin, carbenicillin, nalidixic acid, nitrofurans
• Avoiding the formation of kidney stones ( in phosphate stones such as struvite, carbonate apatite, brushite )
• Inhibition of bacterial growth at a bladder infection
• Element of infusion solutions for parenteral nutrition.

In diagnosis, it is used in the form of 11C -S -methyl-L - methionine as a radiopharmaceutical for the preparation of brain tumors in positron emission tomography.

Application in animal nutrition

DL-methionine (ie the racemate ) is used for supplementing (supplement) of feed. Here, the nutritional value of feed for chickens is increased by small additions of DL -methionine. This is of particular economic benefit if natural feed ingredients have a lack of content of sulfur-containing amino acids ( cysteine ​​/ cystine and methionine). The by far largest amounts of methionine obtained synthetically (> 400 000 tonnes per year ) are used for this purpose.

Application in chemistry

By heating with aqueous hydroiodic acid methionine, the methyl group of methionine is cleaved. Evaporation occurs with elimination of water as the hydriodide cyclization of homocysteine ​​thiolactone.