Tryptophan (symbol Trp or W) 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.
Serine is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC.
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 gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary 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.
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.
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.
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., O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
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.
Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example, an overdose of the analgesic paracetamol (acetaminophen) can fatally damage the liver, partly through its production of reactive oxygen species.
Quinolinic acid, also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin.
Indole is an organic compound with the formula C6H4CCNH3. Indoles are derivatives of indole where one or more H's have been replaced by other groups. Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are widely distributed in nature, most notably as amino acid tryptophan and neurotransmitter serotonin.
Type 3 diabetes is a proposed pathological linkage between Alzheimer's disease and certain features of type 1 and type 2 diabetes. Specifically, the term refers to a set of common biochemical and metabolic features seen in the brain in Alzheimer's disease, and in other tissues in diabetes; it may thus be considered a "brain-specific type of diabetes." It was recognized at least as early as 2005 that some features of brain function in Alzheimer's disease mimic those that underlie diabetes. However, the concept of type 3 diabetes is controversial, and as of 2021 it was not an officially recognized diagnosis.
Cymserine is a drug related to physostigmine, which acts as a reversible cholinesterase inhibitor, with moderate selectivity (15×) for the plasma cholinesterase enzyme butyrylcholinesterase, and relatively weaker inhibition of the better-known acetylcholinesterase enzyme. This gives it a much more specific profile of effects that may be useful for treating Alzheimer's disease without producing side effects such as tremors, lacrimation, and salivation that are seen with the older nonselective cholinesterase inhibitors currently used for this application, such as donepezil. A number of cymserine derivatives have been developed with much greater selectivity for butyrylcholinesterase, and both cymserine and several of its analogues have been tested in animals, and found to increase brain acetylcholine levels and produce nootropic effects, as well as reducing levels of amyloid precursor protein and amyloid beta, which are commonly used biomarkers for the development of Alzheimer's disease.
Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of ethanol fermentation. It was first described by Felix Ehrlich in 1912. It is also produced by the trypanosomal parasite in sleeping sickness.
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.
Indolyl-3-acryloylglycine, also known as trans-indolyl-3-acryloylglycine, or IAG for short, is a compound consisting of an indole group attached to an acrylic acid moiety, which is in turn attached to a glycine molecule. This compound has been shown to isomerize when exposed to light. It is likely a metabolic intermediate in the biosynthesis of tryptophan, and is synthesized from tryptophan via indolepropionic acid and indoleacrylicacid (IAcrA). It is also likely that IAcrA is converted into IAG in the gut wall. It may also be produced by certain elements of the mammalian gut microbiota by phenylalanine ammonia-lyase. Identifiable in the urine by high-performance liquid chromatography, it may be a biomarker for autism spectrum disorders, as demonstrated by the research of Paul Shattock and other researchers from Australia. These researchers have reported that urinary levels of IAG are much higher in autistic children than in controls; however, other researchers have found no association between IAG concentrations in the urine and autism. Its excretion in the urine may also be changed in Hartnup disease and celiac disease, as well as photodermatosis, muscular dystrophy, and liver cirrhosis.
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.
Indolepropionamide (IPAM) is a chemical compound with the molecular formula C11H12N2O. In vivo (rats), IPAM markedly reduced the proton potential collapse induced by the mitochondrial toxins to nearly baseline levels in both young and old rats and demonstrated free-radical scavenging properties. IPAM was shown to increase complex I and complex IV activity in the mitochondrial electron transport chain, however complex II and complex III were left unchanged. Decreased activity of complexes I and IV results in an inhibition of electron transport that is associated with higher production of ROS. IPAM can also act as a recyclable electron and proton carrier, facilitating reversible endogenous radical and redox reactions, and thereby enabling the formation of a proton gradient that drives mitochondrial ATP synthesis. Thus, IPAM acts as a stabilizer of energy metabolism in mitochondria, thereby reducing the production of reactive oxygen species.
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. 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. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.
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.
Indoleacetate decarboxylase (IAD) is a glycyl radical enzyme that catalyses the decarboxylation of indoleacetate to form skatole, which is a malodorous organic compound that gives animal faeces their characteristic smell. This decarboxylation is the last step of the tryptophan fermentation in some types of anaerobic bacteria.
