Names | |||
---|---|---|---|
Preferred IUPAC name (2S)-3-(2-Sulfanylidene-2,3-dihydro-1H-imidazol-4-yl)-2-(trimethylazaniumyl)propanoate | |||
Other names L-Ergothioneine; (+)-Ergothioneine; Thiasine; Sympectothion; Ergothionine; Erythrothioneine; Thiolhistidinebetaine | |||
Identifiers | |||
3D model (JSmol) | |||
ChEBI | |||
ChemSpider | |||
ECHA InfoCard | 100.007.131 | ||
KEGG | |||
PubChem CID | |||
UNII | |||
CompTox Dashboard (EPA) | |||
| |||
| |||
Properties | |||
C9H15N3O2S | |||
Molar mass | 229.30 g/mol | ||
Appearance | white solid | ||
Melting point | 275 to 277 °C (527 to 531 °F; 548 to 550 K) | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Ergothioneine is a naturally occurring amino acid and is a thiourea derivative of histidine, containing a sulfur atom on the imidazole ring. [1] This compound occurs in relatively few organisms, notably actinomycetota, cyanobacteria, and certain fungi. [2] [3] Ergothioneine was discovered by Charles Tanret in 1909 and named after the ergot fungus from which it was first purified, [4] with its structure being determined in 1911. [5] [6]
In humans, ergothioneine is acquired exclusively through the diet and accumulates in erythrocytes, bone marrow, liver, kidney, seminal fluid, and eyes. [7] Although the effect of ergothioneine in vivo is under preliminary research, its physiological role in humans is unknown. [7] Ergothioneine is sold as a dietary supplement. [8]
Ergothioneine has been found in bacteria, plants, and animals, sometimes at millimolar levels. [9] Foods found to contain ergothioneine include liver, kidney, black beans, kidney bean, and oat bran, with the highest levels in bolete and oyster mushrooms. [9] [10] Levels can be variable, even within species and some tissues can contain much more than others. In the human body, the largest amounts of ergothioneine are found in erythrocytes, eye lens, semen, [6] and skin. [11]
Although many species contain ergothioneine, only a few make it; the others absorb it from their diet or, in the case of plants, from their environment. [12] Biosynthesis has been detected in Actinomycetota, such as Mycobacterium smegmatis and certain fungi, such as Neurospora crassa . [2]
The metabolic pathway to produce ergothioneine starts with the methylation of histidine to produce histidine betaine (hercynine). The sulfur atom is then incorporated from cysteine. [9] [13] The biosynthetic genes of ergothioneine have been described in Mycobacterium smegmatis , [14] Neurospora crassa , [15] and Schizosaccharomyces pombe . [16]
Other species of bacteria, such as Bacillus subtilis , Escherichia coli , Proteus vulgaris , and Streptococcus , as well as fungi in the Saccharomycotina cannot make ergothioneine. [17] [18]
Ergothioneine is a thiourea derivative of the betaine of histidine and contains a sulfur atom bonded to the 2-position of the imidazole ring. [19] Typical of thioureas, ergothioneine is less reactive than typical thiols such as glutathione towards alkylating agents like maleimides. It also resists oxidation by air. [9] However, ergothioneine can be slowly oxidized over several days to the disulfide form in acidic solutions. [20]
Various derivatives of ergothioneine have been reported in the literature, such as S-methyl-ergothioneine [21] or selenium-containing selenoneine. [22]
Although potential effects of ergothioneine are under preliminary research, its physiological role in vivo has not been determined. [1] [7]
The Panel on Dietetic Products for the European Food Safety Authority reported safe daily limits of 2.82 mg/kg of body weight for infants, 3.39 mg/kg for small children, and 1.31 mg/kg for adults, including pregnant and breastfeeding women. [8]
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol, or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.
Methionine is an essential amino acid in humans.
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the deprotonated –COO− form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH. Initially thought essential only for infants, it has now been shown in longer-term studies to be essential for adults also. It is encoded by the codons CAU and CAC.
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).
Metallothionein (MT) is a family of cysteine-rich, low molecular weight proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological and xenobiotic heavy metals through the thiol group of its cysteine residues, which represent nearly 30% of its constituent amino acid residues.
Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in vertebrates.
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine deficiency affects two billion people and is the leading preventable cause of intellectual disability.
Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O−
2, OH and H2O2. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. Depending on the body's state, ribulose 5-phosphate can reversibly isomerize to ribose 5-phosphate. Ribulose 5-phosphate can alternatively undergo a series of isomerizations as well as transaldolations and transketolations that result in the production of other pentose phosphates as well as fructose 6-phosphate and glyceraldehyde 3-phosphate.
Pantothenate kinase (EC 2.7.1.33, PanK; CoaA) is the first enzyme in the Coenzyme A (CoA) biosynthetic pathway. It phosphorylates pantothenate (vitamin B5) to form 4'-phosphopantothenate at the expense of a molecule of adenosine triphosphate (ATP). It is the rate-limiting step in the biosynthesis of CoA.
NAD+ kinase (EC 2.7.1.23, NADK) is an enzyme that converts nicotinamide adenine dinucleotide (NAD+) into NADP+ through phosphorylating the NAD+ coenzyme. NADP+ is an essential coenzyme that is reduced to NADPH primarily by the pentose phosphate pathway to provide reducing power in biosynthetic processes such as fatty acid biosynthesis and nucleotide synthesis. The structure of the NADK from the archaean Archaeoglobus fulgidus has been determined.
Glutamate–cysteine ligase (GCL) EC 6.3.2.2), previously known as γ-glutamylcysteine synthetase (GCS), is the first enzyme of the cellular glutathione (GSH) biosynthetic pathway that catalyzes the chemical reaction:
The enzyme chorismate synthase catalyzes the chemical reaction
Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.
Glutaredoxin 2 (GLRX2) is an enzyme that in humans encoded by the GLRX2 gene. GLRX2, also known as GRX2, is a glutaredoxin family protein and a thiol-disulfide oxidoreductase that maintains cellular thiol homeostasis. This gene consists of four exons and three introns, spanned 10 kilobase pairs, and localized to chromosome 1q31.2–31.3.
Pyocyanin (PCN−) is one of the many toxic compounds produced and secreted by the Gram negative bacterium Pseudomonas aeruginosa. Pyocyanin is a blue secondary metabolite, turning red below pH 4.9, with the ability to oxidise and reduce other molecules and therefore kill microbes competing against P. aeruginosa as well as mammalian cells of the lungs which P. aeruginosa has infected during cystic fibrosis. Since pyocyanin is a zwitterion at blood pH, it is easily able to cross the cell membrane. There are three different states in which pyocyanin can exist: oxidized (blue), monovalently reduced (colourless) or divalently reduced (red). Mitochondria play an important role in the cycling of pyocyanin between its redox states. Due to its redox-active properties, pyocyanin generates reactive oxygen species.
Mycosporine-like amino acids (MAAs) are small secondary metabolites produced by organisms that live in environments with high volumes of sunlight, usually marine environments. The exact number of compounds within this class of natural products is yet to be determined, since they have only relatively recently been discovered and novel molecular species are constantly being discovered; however, to date their number is around 30. They are commonly described as “microbial sunscreens” although their function is believed not to be limited to sun protection. MAAs represent high potential in cosmetics, and biotechnological applications. Indeed, their UV-absorbing properties would allow to create products derived from natural photoprotectors, potentially harmless to the environment and efficient against UV damage.
Helmut Sies is a German physician, biochemist and university professor. He was the first to demonstrate the existence of hydrogen peroxide as a normal attribute of aerobic life in 1970, and he introduced the concept of Oxidative stress in 1985. He also worked on the biological strategies of antioxidant defense and the biochemistry of nutritional antioxidants.
Selenoneine is a selenium containing ergothioneine derivative where the selenium (Se) atom replaces a sulfur atom. It can be systematically named as.