8. 예방
계란과 붉은 고기의 섭취를 적당히 하여
장내 TMA생성을 줄인다.
9. 역사
TMAO는 해양 갑각류와 해양 어류의 조직에서
발견되며 수압이 단백질을 왜곡시켜
동물을 죽이는 것을 방지합니다.
TMAO의 농도는 동물이 사는 깊이에 따라 증가합니다.
TMAO는 기록된 수심 8,076m의
마리아나 해구에서 발견된 가장 깊은 생물종인
Pseudoliparis swirei 에서
고농도 로 발견됩니다 . [1] [2]
10. 기타
● 트리메틸아민 N- 옥사이드는
연체동물, 갑각류, 모든 해양 어류 및 경골어류에서 발견되는 삼투질 입니다.
압력의 단백질 불안정화 효과를 상쇄하는 역할을 하는 단백질 안정제입니다.
일반적으로 깊은 수심에 사는 동물의 몸은 압력 저항 생체 분자와 작은 유기 분자가 세포에 존재함으로써 고압 환경에 적응합니다.
압전액(piezolytes)으로 알려진 그 중 TMAO가 가장 풍부합니다.
이 압전물은 단백질이 큰 압력에서
제대로 기능하는 데 필요한 유연성을 제공합니다. [1] [2] [4] [5] [6]
TMAO 는 해산물 분해의 특징인 주요 비린냄새 물질인 트리메틸아민 (TMA) 으로 분해됩니다.
● 화학
TMAO는 과산화수소로 처리하여 트리메틸아민에서 합성할 수 있습니다. [7]
H 2 O 2 + (CH 3 ) 3 N → H 2 O + (CH 3 ) 3 NO
이수화물은 디메틸포름아미드 로부터 공비 증류에 의해 탈수됩니다 . [8]
● 트리메틸아미노뇨증
플라빈 함유 모노옥시게나제 3 ( FMO3 ) 효소 생산의 드문 결함입니다 . [14] [15]
트리메틸아미노뇨증을 앓고 있는 사람들은
콜린에서 파생된 트리메틸아민을
트리메틸아민 옥사이드로 전환할 수 없습니다.
그런 다음 트리메틸아민이 축적되어
사람의 땀, 소변 및 호흡으로 방출되어
강한 비린내를 발산합니다.
● 논쟁
Clouatre et al. 콜린 공급원과 식이 L-카르니틴은 혈액 TMAO의 유의한 상승에 기여하지 않는다고 주장합니다. 그러나 이 논쟁을 제기하는 데 사용된 연구는 L-카르니틴 보충제를 제조 및 판매하는 Lonza, Inc.의 후원을 받았으므로 그들의 논쟁은 편향된 것으로 간주될 수 있습니다. 대신 식단에서 TMAO의 주요 공급원은 생선입니다. [20]
그리고 심혈관 질환과 TMAO 사이의 연관성은
마우스 연구에서 논쟁의 여지가 있습니다. [21]
TMAO의 또 다른 공급원은
식이성 포스파티딜콜린이며,
다시 장내 세균 작용을 통해 이루어집니다.
포스파티딜 콜린은 달걀 노른자와
일부 육류에 고농도로 존재합니다.
TMAO와 심혈관 질환 사이의 명백한 인과 관계를 반박하는 가장 강력한 증거는 순환 TMAO 수준과
심근 경색 또는 관상 동맥 질환 사이의 중요한 연관성을 감지하지 못한 Mendelian 무작위 배정 연구에서 비롯됩니다. [22]
● 몰리브덴 함유 효소는 포유류에 존재합니다.
소위 미토콘드리아 아미드옥심 환원 성분(mARC)은 mARC1 및 mARC2의 두 가지 이소형으로 존재하는 것으로 밝혀졌으며, 둘 다 비생리학적 N-산화물을 비롯한 다양한 N-산소화 화합물을 환원할 수 있습니다. [31]
완두콩과 검은콩은 식이 몰리브덴의 가장 풍부한 식품 공급원 중 하나입니다. (??)
● 콜린의 구조적 유사체
3,3-디메틸-1-부탄올 (DMB)은 생쥐와 인간 대변에서 미생물 TMA 형성을 억제하여
콜린 또는 카르니틴 보충 후
혈장 TMAO 수준을 감소시킵니다. [13]
발사믹 식초, 적포도주,
냉압착 엑스트라 버진 올리브 오일과
포도씨 오일에서 발견 됩니다. [13]
Trimethylamine N-oxide (TMAO) is an organic compound with the formula (CH3)3NO. It is in the class of amine oxides. Although the anhydrous compound is known, trimethylamine N-oxide is usually encountered as the dihydrate. Both the anhydrous and hydrated materials are white, water-soluble solids.
TrimethylamineN-oxideNamesPreferred IUPAC name
N,N-Dimethylmethanamine N-oxide
Other names
Trimethylamine oxide, TMAO, TMANO
Infobox references
TMAO is found in the tissues of marine crustaceans and marine fish, where it prevents water pressure from distorting proteins and thus killing the animal. The concentration of TMAO increases with the depth at which the animal lives; TMAO is found in high concentrations in the deepest-living described species, Pseudoliparis swirei, which was found in the Mariana Trench, at a recorded depth of 8,076 m (26,496 ft).[1][2]
TMAO is a product of the oxidation of trimethylamine, a common metabolite of choline in animals.[3]
Marine animalsEdit
Trimethylamine N-oxide is an osmolyte found in molluscs, crustaceans, and all marine fishes and bony fishes. It is a protein stabilizer that serves to counteract the protein-destabilizing effects of pressure. In general, the bodies of animals living at great depths are adapted to high pressure environments by having pressure-resistant biomolecules and small organic molecules present in their cells, known as piezolytes, of which TMAO is the most abundant. These piezolytes give the proteins the flexibility they need to function properly under great pressure.[1][2][4][5][6]
TMAO decomposes to trimethylamine (TMA), which is the main odorant that is characteristic of degrading seafood.
ChemistryEdit
TMAO can be synthesized from trimethylamine by treatment with hydrogen peroxide:[7]
H2O2 + (CH3)3N → H2O + (CH3)3NO
The dihydrate is dehydrated by azeotropic distillation from dimethylformamide.[8]
Laboratory applicationsEdit
Trimethylamine oxide is used in protein folding experiments to counteract the unfolding effects of urea.[9]
In the organometallic chemistry reaction of nucleophilic abstraction, Me3NO is employed as a decarbonylation agent according to the following stoichiometry:
M(CO)n + Me3NO + L → M(CO)n−1L + Me
Laboratory applicationsEdit
Trimethylamine oxide is used in protein folding experiments to counteract the unfolding effects of urea.[9]
In the organometallic chemistry reaction of nucleophilic abstraction, Me3NO is employed as a decarbonylation agent according to the following stoichiometry:
M(CO)n + Me3NO + L → M(CO)n−1L + Me3N + CO2
This reaction is used to decomplex organic ligands from metals, e.g. from (diene)Fe(CO)3.[7]
It is used in certain oxidation reactions, e.g. the conversion of alkyl iodides to the corresponding aldehyde.[10]
Effects on protein stabilityEdit
The effects of TMAO on the backbone and charged residues of peptides are found to stabilize compact conformations,[11] whereas effects of TMAO on nonpolar residues lead to peptide swelling. This suggests competing mechanisms of TMAO on proteins, which accounts for hydrophobic swelling, backbone collapse, and stabilization of charge-charge interactions. These mechanisms are observed in Trp cage.[12]
Microbiotic associationsEdit
The order Clostridiales, the genus Ruminococcus, and the taxon Lachnospiraceae are positively associated with TMA and TMAO levels.[13] In contrast, proportions of S24-7, an abundant family from Bacteroidetes, are inversely associated with TMA and TMAO levels.[13]
DisordersEdit
TrimethylaminuriaEdit
Main article: Trimethylaminuria
Trimethylaminuria is a rare defect in the production of the enzyme flavin-containing monooxygenase 3 (FMO3).[14][15] Those suffering from trimethylaminuria are unable to convert choline-derived trimethylamine into trimethylamine oxide. Trimethylamine then accumulates and is released in the person's sweat, urine, and breath, giving off a strong fishy odor.
Cardiovascular diseaseEdit
A study published in 2013, assessing 513 adults with a history of major adverse cardiovascular events, an average age of 68, and 69% of whom previously or currently smoke, may indicate that high levels of TMAO in the blood are associated with an increased risk of additional cardiovascular events.[16]
BackgroundEdit
The concentration of TMAO in the blood increases after consuming foods containing carnitine[17] or lecithin[16] if the bacteria that convert those substances to TMAO are present in the gut.[18] High concentrations of carnitine are found in red meat, some energy drinks, and some dietary supplements. Some types of normal gut bacteria (e.g. species of Acinetobacter) in the human microbiome convert dietary carnitine to TMAO. TMAO alters cholesterol metabolism in the intestines, in the liver, and in artery walls. In the presence of TMAO, there is increased deposition of cholesterol in, and decreased removal of cholesterol from peripheral cells such as those in artery walls.[19] Lecithin is found in soy, eggs,[18] as an ingredient in processed food, is sold as a dietary supplement, is used as an emulsifier, and is used to prevent sticking (for example in non-stick cooking spray).
ControversyEdit
Clouatre et al. argue that choline sources and dietary L-carnitine do not contribute to a significant elevation of blood TMAO. However, the study used to raise this dispute was sponsored by Lonza, Inc., who manufactures and sells an L-Carnitine supplement, so their dispute may be considered biased. Instead the main source of TMAO in the diet is fish.[20] And the link between cardiovascular diseases and TMAO is disputed in a mouse study.[21]
Another source of TMAO is dietary phosphatidylcholine, again by way of bacterial action in the gut. Phosphatidyl choline is present at high concentration in egg yolks and some meats. The strongest evidence to contradict the apparent causal relationship between TMAO and cardiovascular disease comes from a Mendelian randomization study that failed to detect a significant association between circulating TMAO levels and myocardial infarction or coronary artery disease.[22]
Hypertension and thrombosisEdit
It has been suggested that TMAO may be involved in the regulation of arterial blood pressure and etiology of hypertension[23] and thrombosis (blood clots) in atherosclerotic disease.[24] A 2017 meta-analysis found higher circulating TMAO was associated with 23% higher risk of cardiovascular events and a 55% higher risk of mortality.[25]
Notably, toxic effects of TMA were described in several clinical and experimental papers in the mid 20th century[26] and very recent studies show deleterious effect of TMA on the circulatory system.[27][28][29] Furthermore, due to the obvious toxicity and, at the same time, widespread use in industry, various exposure limit guidelines with a detailed description of toxicity are available such as “Recommendation from the Scientific Committee on Occupational Exposure Limits” by the European Union Commission.[30] Therefore, it seems that it is TMA but not TMAO that may be a marker and mediator of cardiovascular risk.
Management of elevated levelsEdit
Vegan and vegetarian diets appear to select against gut flora that metabolize carnitine (in favor of other gut flora more coordinated with their food supply). This apparent difference in their microbiome is associated with substantially reduced gut bacteria capable of converting carnitine to trimethylamine, which is later metabolized in the liver to TMAO.[17]
Molybdenum containing enzymes exist in mammals. The so-called mitochondrial amidoxime reducing component (mARC) has been found to exist in two isoforms, mARC1 and mARC2, both being capable of reducing a variety of N-oxygenated compounds, including nonphysiological N-oxides.[31] Green peas and black beans are believed[by whom?] to be among the richest food sources of dietary molybdenum.
3,3-Dimethyl-1-butanol (DMB), a structural analog of choline, inhibits microbial TMA formation in mice and in human feces, thereby reducing plasma TMAO levels after choline or carnitine supplementation.[13] It is found in some balsamic vinegars, red wines, and some cold-pressed extra virgin olive oils and grape seed oils.[13]
Resveratrol has been shown to reduce TMAO in mice by remodeling gut microbiota.[32]
https://en.m.wikipedia.org/wiki/Trimethylamine_N-oxide#
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