Names | |
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Preferred IUPAC name 1H-Indol-3-yl hydrogen sulfate | |
Other names 3-Indoxylsulfate; 3-Indoxylsulfuric acid; Indol-3-yl sulfate | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
DrugBank | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C8H7NO4S | |
Molar mass | 213.21 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary L-tryptophan that acts as a cardiotoxin and uremic toxin. [1] [2] [3] High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. [1] [2] [3] As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis. [1] [2]
Indoxyl sulfate is a metabolite of dietary L-tryptophan that is synthesized through the following metabolic pathway: [3] [4] [5]
Indole is produced from L-tryptophan in the human intestine via tryptophanase-expressing gastrointestinal bacteria. [3] Indoxyl is produced from indole via enzyme-mediated hydroxylation in the liver; [3] [4] in vitro experiments with rat and human liver microsomes suggest that the CYP450 enzyme CYP2E1 hydroxylates indole into indoxyl. [4] Subsequently, indoxyl is converted into indoxyl sulfate by sulfotransferase enzymes in the liver; [4] [5] based upon in vitro experiments with recombinant human sulfotransferases, SULT1A1 appears to be the primary sulfotransferase enzyme involved in the conversion of indoxyl into indoxyl sulfate. [5]
Tryptophan metabolism by human gastrointestinal microbiota ( ) |
Occasionally in urinary tract infections, bacteria produce indoxyl phosphatase which splits indoxyl sulfate forming indigo and indirubin creating dramatic purple urine. [9] Indoxyl sulfate is also a product of indole metabolism, which is produced from tryptophan by intestinal flora, such as Escherichia coli. [10]
Tryptophan is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3. It is encoded by the codon UGG.
Lactobacillus is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus Lactobacillus comprised over 260 phylogenetically, ecologically, and metabolically diverse species; a taxonomic revision of the genus assigned lactobacilli to 25 genera.
The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.
Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure. It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.
Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a trimethylated derivative of ammonia. TMA is widely used in industry. At higher concentrations it has an ammonia-like odor, and can cause necrosis of mucous membranes on contact. At lower concentrations, it has a "fishy" odor, the odor associated with rotting fish.
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods.
Indole-3-acetic acid is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.
Indican is a colourless organic compound, soluble in water, naturally occurring in Indigofera plants. It is a precursor of indigo dye.
Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.
N-Acetylserotonin O-methyltransferase, also known as ASMT, is an enzyme which catalyzes the final reaction in melatonin biosynthesis: converting Normelatonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway. The enzyme also catalyzes a second reaction in tryptophan metabolism: the conversion of 5-hydroxy-indoleacetate to 5-methoxy-indoleacetate. The other enzyme which catalyzes this reaction is n-acetylserotonin-o-methyltransferase-like-protein.
Phenylacetylglutamine is a product formed by the conjugation of phenylacetate and glutamine. It is a common metabolite that occurs naturally in human urine.
Indole is an aromatic, heterocyclic, organic compound with the formula C8H7N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.
Clostridium sporogenes is a species of Gram-positive bacteria that belongs to the genus Clostridium. Like other strains of Clostridium, it is an anaerobic, rod-shaped bacterium that produces oval, subterminal endospores and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized animals, it has a mutualistic rather than pathogenic interaction with the host.
Quercetin 3-sulfate is a plasma human metabolite of quercetin. It is the sulfate conjugate of quercetin.
The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The "microbiota–gut–brain axis" includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.
Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. Its precursors – ellagic acids and ellagitannins – are ubiquitous in nature, including edible plants, such as pomegranates, strawberries, raspberries, walnuts, and others.
3-Indolepropionic acid (IPA), or indole-3-propionic acid, has been studied for its therapeutic therapeutic value in the treatment of Alzheimer's disease. As of 2022 IPA shows potential in the treatment of this disease, though the therapeutic effect of IPA depends on dose and time of therapy initiation.
6-Formylindolo[3,2-b]carbazole (FICZ) is a chemical compound with the molecular formula C19H12N2O. It is a nitrogen heterocycle, having an extremely high affinity (Kd = 7 x 10−11M) for binding to the aryl hydrocarbon receptor (AHR).
Indole-3-carbaldehyde (I3A), also known as indole-3-aldehyde and 3-formylindole, is a metabolite of dietary L-tryptophan which is synthesized by human gastrointestinal bacteria, particularly species of the Lactobacillus genus. I3A is a biologically active metabolite which acts as a receptor agonist at the aryl hydrocarbon receptor in intestinal immune cells, in turn stimulating the production of interleukin-22 which facilitates mucosal reactivity.
4-Ethylphenyl sulfate (4EPS) is a metabolite produced by gut bacteria, which can be toxic when present in large amounts. Elevated levels of this metabolite have been associated with some medical conditions including chronic kidney disease and autism.
Lactobacillus spp. convert tryptophan to indole-3-aldehyde (I3A) through unidentified enzymes [125]. Clostridium sporogenes convert tryptophan to IPA [6], likely via a tryptophan deaminase. ... IPA also potently scavenges hydroxyl radicals
Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes.
[Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity.