出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/17 17:32:26」(JST)
| メチオニン | |
|---|---|
|
IUPAC名
Methionine |
|
|
別称
2-amino-4-(methylthio)butanoic acid
|
|
| 識別情報 | |
| 略称 | Met, M |
| CAS登録番号 | 59-51-8 , 63-68-3 (L-isomer) , 348-67-4 (D-isomer) |
| PubChem | 876 |
| ChemSpider | 853 , 5907 (L体) |
| UNII | 73JWT2K6T3 |
| EINECS番号 | 200-432-1 |
| KEGG | D04983 |
| ChEMBL | CHEMBL42336 |
| ATC分類 | V03AB26,QA05BA90, QG04BA90 |
|
SMILES
|
|
|
InChI
|
|
| 特性[2] | |
| 化学式 | C5H11NO2S |
| モル質量 | 149.21 g mol−1 |
| 外観 | White crystalline powder |
| 密度 | 1.340 g/cm3 |
| 融点 |
281 °C（分解） |
| 水への溶解度 | 可溶 |
| 酸解離定数 pKa | 2.28 (カルボキシル基), 9.21 (アミノ基)[1] |
| 特記なき場合、データは常温 (25 °C)・常圧 (100 kPa) におけるものである。 | |
メチオニン（methionine, メサイオニン）は必須アミノ酸のひとつで、側鎖に硫黄を含んだ疎水性のアミノ酸である。
血液中のコレステロール値を下げ、活性酸素を取り除く作用がある。ピルビン酸へと代謝する経路が存在するため、糖原性をもつ。
硫黄移動経路によりシステイン、カルニチン、タウリンの生合成や、レシチンのリン酸化などリン脂質の生成に関与する。メチオニンが不適切な変換を受けると動脈硬化症が起こることがある。メチオニンはキレート剤でもある。メチオニンの誘導体である S-アデノシルメチオニン (SAM) はメチル基の供与体としてはたらく。
対応するコドンが単一なアミノ酸は2つだけであり、1つは AUG でコードされるメチオニン、もう1つは UGG でコードされるトリプトファンである。コドン AUG はリボソームに mRNA からのタンパク質翻訳を「開始」させるメッセージを送る開始コドンとしても重要である。結果として真核生物および古細菌では全てのタンパク質のN末端はメチオニンになる。しかしながら、これは翻訳中のタンパク質に限るものであり、普通は翻訳完了後に修飾を受けて取り除かれる。メチオニンはN末端以外の位置にも出現する。
メチオニンを多く含む食物として果物、肉、野菜、ナッツ、マメ科の植物があげられる。特にホウレンソウ、グリーンピース、ニンニク、ある種のチーズ、トウモロコシ、ピスタチオ、カシューナッツ、インゲンマメ、豆腐、テンペに豊富に見られる。肉類では鶏肉、牛肉、魚肉など大部分のものに含まれる。
メチオニンはヒトの体内で作り出せない必須アミノ酸である。一方、植物や微生物はアスパラギン酸とシステインから生合成を行う。まずアスパラギン酸は β-アスパルテートセミアルデヒドに変換されるが、これはリシンやスレオニンの生合成経路でも重要である。次にホモセリンアシルトランスフェラーゼによってホモセリンに良い脱離基が付加され、システインと反応してシスタチオニンとなる。これが開裂させられてホモシステインを与え、葉酸（テトラヒドロフォレート、THF）でメチル化されてメチオニンとなる。補因子として、シスタチオニン-γ-シンターゼとシスタチオニン-β-リアーゼは共にピリドキシル-5'-ホスフェートを、ホモシステインメチルトランスフェラーゼはビタミンB12を必要とする。
哺乳類はメチオニンを生合成できないが、様々な生化学的過程において利用している。メチオニンはメチオニンアデノシルトランスフェラーゼによって S-アデノシルメチオニンに変換され、これはメチルトランスフェラーゼによるメチル基移動（メチル化）に用いられる。メチル基の移動後は S-アデノシルホモシステイン (SAH) となり、アデノシルホモシステイナーゼでホモシステインに変換される。
ホモシステインの行く先は2つある。1つはメチオニンシンターゼによってメチオニンに戻る経路で、もう1つはシステインに変換される経路である。後者では、まずシスタチオニン-β-シンターゼでセリンと結合されてシスタチオニンとなる。次に（上記の生合成過程ではシスタチオニン-β-リアーゼで分解されるが）、シスタチオニン-β-リアーゼによってシステインと α-ケト酪酸になる。さらに α-ケト酸デヒドロゲナーゼによって α-ケト酪酸はプロピオニルCoAに変換され、最終的にはスクシニルCoA（コハク酸CoA）へと代謝される。
プロピオニルCoAはビオチン依存性酵素であるプロピオニルCoAカルボキシラーゼによって(S)-メチルマロニルCoAに変換される。この生成物はさらにメチルマロニルCoAエピメラーゼによって(R)-メチルマロニルCoAに変換される。(R)-メチルマロニルCoAは、メチルマロニルCoAムターゼによってスクシニルCoAに変換されるが、この酵素は炭素-炭素結合の移動を触媒するためのコバラミン（ビタミンB12）を要する。
| ウィキメディア・コモンズには、メチオニンに関連するカテゴリがあります。 |
|
|||||||||||||||||||||||||||||||
| Names | |
|---|---|
| IUPAC name
Methionine
|
|
| Other names
2-amino-4-(methylthio)butanoic acid
|
|
| Identifiers | |
| Abbreviations | Met, M |
| ATC code | V03AB26 QA05BA90, QG04BA90 |
|
CAS Registry Number
|
59-51-8 Y 63-68-3 (L-isomer) Y |
| ChEBI | CHEBI:16811 Y |
| ChEMBL | ChEMBL42336 N |
| ChemSpider | 853 Y 5907 (L-isomer) Y |
| EC number | 200-432-1 |
|
InChI
|
|
| Jmol-3D images | Image Image |
| KEGG | D04983 Y |
| PubChem | 876 |
|
SMILES
|
|
| UNII | 73JWT2K6T3 Y |
| Properties[2] | |
|
Chemical formula
|
C5H11NO2S |
| Molar mass | 149.21 g·mol−1 |
| Appearance | White crystalline powder |
| Density | 1.340 g/cm3 |
| Melting point | 281 °C (538 °F; 554 K) decomposes |
|
Solubility in water
|
Soluble |
| Acidity (pKa) | 2.28 (carboxyl), 9.21 (amino)[1] |
| Supplementary data page | |
|
Structure and
properties |
Refractive index (n), Dielectric constant (εr), etc. |
|
Thermodynamic
data |
Phase behaviour solid–liquid–gas |
|
Spectral data
|
UV, IR, NMR, MS |
|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|
|
| N verify (what is: Y/N?) | |
| Infobox references | |
Methionine (/mɛˈθaɪ.ɵniːn/ or /mɛˈθaɪ.ɵnɪn/; abbreviated as Met or M)[3] is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This amino acid is classified as nonpolar as it has a straight side chain that possess a S-methyl thioether (i.e. C–S–C bonding) at the γ-carbon. It is an essential amino acid in all metazoa.[4] This amino-acid is coded by the initiation codon AUG which also indicates mRNA's coding region where translation into protein begins.
Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Excluding the few exceptions where methionine may act as a redox sensor (e.g. [5]), methionine residues do not have a catalytic role.[6] This is in contrast to cysteine residues, where the thiol group has a catalytic role in many proteins.[6] The thioether does however have a minor structural role due to the stability effect of S/π interactions between the side chain sulfur atom and aromatic amino acids in one-third of all known protein structures.[6] This lack of a strong role is reflected in experiments where little effect is seen in proteins where methionine is replaced by norleucine, a straight hydrocarbon sidechain amino acid which lacks the thioether.[7] It has been conjectured that norleucine was present in early versions of the genetic code, but methionine intruded into the final version of the genetic code due to the fact it is used in the cofactor S-adenosyl methionine (SAM).[8] This situation is not unique and may have occurred with ornithine and arginine.[9]
Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code (tryptophan, encoded by UGG, is the other). In reflection to the evolutionary origin of its codon, the other AUN codons encode isoleucine, which is also a hydrophobic amino acid. In the mitochondrial genome of several organisms, including metazoa and yeast, the codon AUA also encodes for methionine. In the standard genetic code AUA codes for isoleucine and the respective tRNA (ileX in Escherichia coli) uses the unusual base lysidine (bacteria) or agmatine (archaea) to discriminate against AUG.[10][11]
The methionine codon AUG is also the most common start codon. A "Start" codon is message for a ribosome that signals the initiation of protein translation from mRNA when the AUG codon is in a Kozak consensus sequence. As a consequence, methionine is often incorporated into the N-terminal position of proteins in eukaryotes and archaea during translation, although it can be removed by post-translational modification. In bacteria, the derivative N-formylmethionine is used as the initial amino acid.
The methionine-derivative S-adenosyl methionine (SAM) is a cofactor that serves mainly as a methyl donor. SAM is composed of an adenosyl molecule (via 5' carbon) attached to the sulfur of methionine, therefore making it a sulfonium cation (i.e. three substituents and positive charge). The sulfur acts as soft Lewis acid (i.e. donor/electrophile) allows the S-methyl group to be transferred to an oxygen, nitrogen or aromatic system, often with the aid of other cofactors such as cobalamin (vitamin B12 in humans). Some enzymes use SAM to initiate a radical reaction, these are called radical SAM enzymes. As a result of the transfer of the methyl group, S-adenosyl-homocysteine is obtained. In bacteria, this is either regenerated by methylation or is salvaged by removing the adenine and the homocysteine leaving the compound dihydroxypentandione to spontaneously convert into autoinducer-2, which is excreted as a waste product / quorum signal.
As an essential amino acid, methionine is not synthesized de novo in humans and other animals, who must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine biosynthesis belongs to the aspartate family, along with threonine and lysine (via diaminopimelate, but not via α-aminoadipate). The main backbone is derived from aspartic acid, while the sulfur may come from cysteine, methanethiol or hydrogen sulfide.[6]
The pathway utilising cysteine is called the "Transsulfuration pathway", while the pathway utilising hydrogen sulfide (or methanethiol) is called "direct-sulfurylation pathway".
Cysteine is similarly produced, namely it can be made from an activated serine and either from homocysteine ("reverse trans-sulfurylation route") or from hydrogen sulfide ("direct sulfurylation route"); the activated serine is generally O-acetyl-serine (via CysK or CysM in E. coli), but in Aeropyrum pernix and some other archaea O-phosphoserine is used.[12] CysK and CysM are homologues, but belong to the PLP fold type III clade.
Enzymes involved in the E. coli trans-sulfurylation route of methionine biosynthesis:
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:
Methionine is converted to S-adenosylmethionine (SAM) by (1) methionine adenosyltransferase.
SAM serves as a methyl-donor in many (2) methyltransferase reactions, and is converted to S-adenosylhomocysteine (SAH).
(3) Adenosylhomocysteinase converts SAH to homocysteine.
There are two fates of homocysteine: it can be used to regenerate methionine, or to form cysteine.
Methionine can be regenerated from homocysteine via (4) methionine synthase in a reaction that requires Vitamin B12 as a cofactor.
Homocysteine can also be remethylated using glycine betaine (NNN-trimethyl glycine, TMG) to methionine via the enzyme betaine-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase.
Homocysteine can be converted to cysteine.
This amino acid is also used by plants for synthesis of ethylene. The process is known as the Yang Cycle or the methionine cycle.
Racemic methionine can be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH2CH2SCH3) followed by hydrolysis and decarboxylation.[13]
| Food | g/100g |
|---|---|
| Egg, white, dried, powder, glucose reduced | 3.204 |
| Sesame seeds flour (low fat) | 1.656 |
| Egg, whole, dried | 1.477 |
| Cheese, Parmesan, shredded | 1.114 |
| Brazil nuts | 1.008 |
| Soy protein concentrate | 0.814 |
| Chicken, broilers or fryers, roasted | 0.801 |
| Fish, tuna, light, canned in water, drained solids | 0.755 |
| Beef, cured, dried | 0.749 |
| Bacon | 0.593 |
| Beef, ground, 95% lean meat / 5% fat, raw | 0.565 |
| Pork, ground, 96% lean / 4% fat, raw | 0.564 |
| Wheat germ | 0.456 |
| Oat | 0.312 |
| Peanuts | 0.309 |
| Chickpea | 0.253 |
| Corn, yellow | 0.197 |
| Almonds | 0.151 |
| Beans, pinto, cooked | 0.117 |
| Lentils, cooked | 0.077 |
| Rice, brown, medium-grain, cooked | 0.052 |
High levels of methionine can be found in eggs, sesame seeds, Brazil nuts, fish, meats and some other plant seeds; methionine is also found in cereal grains. Most fruits and vegetables contain very little of it. Most legumes are also low in methionine. However, it is the combination of methionine + cystine which is considered for completeness of a protein.[citation needed] Racemic methionine is sometimes added as an ingredient to pet foods.[15]
There is scientific evidence that restricting methionine consumption can increase lifespans in some animals.[16]
A 2005 study showed methionine restriction without energy restriction extends mouse lifespan.[17]
A study published in Nature showed adding just the essential amino acid methionine to the diet of fruit flies under dietary restriction, including restriction of essential amino acids (EAAs), restored fertility without reducing the longer lifespans that are typical of dietary restriction, leading the researchers to determine that methionine “acts in combination with one or more other EAAs to shorten lifespan.”[18][19]
Several studies showed that methionine restriction also inhibits aging-related disease processes in mice[20][21] and inhibits colon carcinogenesis in rats.[22] In humans, methionine restriction through dietary modification could be achieved through a vegan diet. Veganism being a completely plant based diet is typically very low in methionine, however certain nuts and legumes may provide higher levels.[23]
A 2009 study on rats showed "methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity".[24]
However, since methionine is an essential amino acid, it should not be entirely removed from animals' diets without disease or death occurring over time. For example, rats fed a diet without methionine developed steatohepatitis (fatty liver), anemia and lost two thirds of their body weight over 5 weeks. Administration of methionine ameliorated the pathological consequences of methionine deprivation.[25]
Methionine might also be essential to reversing damaging methylation of glucocorticoid receptors caused by repeated stress exposures, with implications for depression.[26]
Loss of methionine has been linked to senile greying of hair. Its lack leads to a buildup of hydrogen peroxide in hair follicles, a reduction in tyrosinase effectiveness, and a gradual loss of hair color.[27]
Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.[28]
DL-Methionine is sometimes given as a supplement to dogs; it helps keep dogs from damaging grass by reducing the pH of the urine.[29][unreliable source?]
It helps to reduce the chances of stones in dogs by chelating heavy metals, such as mercury, lead and cadmium, and removing them from the body. Methionine is also known to increase the urinary excretion of quinidine by acidifying the urine. Aminoglycoside antibiotics used to treat urinary tract infections work best in alkaline conditions, and urinary acidification from using methionine can reduce its effectiveness. If your dog is on a diet that acidifies the urine, you should not use methionine.[30]
Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.[31]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
| リンク元 | 「ビタミンB12」「メチオニン」「met」「L-methionine」「M」 |
| 拡張検索 | 「adenosylmethionine decarboxylase」「methionine adenosyltransferase」「formylmethionine」 |
部位： ビタミンB12は回腸。 葉酸は空腸。 鉄も空腸、ついでに十二指腸でも。
-CH2-CH2-S-CH3
アデノシルメチオニン脱炭酸酵素、アデノシルメチオニンデカルボキシラーゼ