Instruct: Given a question, retrieve relevant documents that can help answer the question.
Query: What is a metabolite
Metabolites are the intermediates and products of metabolism. Within the context of metabolomics, a metabolite is usually defined as any molecule less than 1 kDa in size. However, there are exceptions to this depending on the sample and detection method. For example, macromolecules such as lipoproteins and albumin are reliably detected in NMR-based metabolomics studies of blood plasma. In plant-based metabolomics, it is common to refer to "primary" and "secondary" metabolites. A primary metabolite is directly involved in the normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has important ecological function. Examples include antibiotics and pigments. By contrast, in human-based metabolomics, it is more common to describe metabolites as being either endogenous (produced by the host organism) or exogenous. Metabolites of foreign substances such as drugs are termed xenometabolites.
The metabolome reflects the interaction between an organism’s genome and its environment. As a result, an organism’s metabolome can serve as an excellent probe of its phenotype (i.e. the product of its genotype and its environment). Metabolites can be measured (identified, quantified or classified) using a number of different technologies including NMR spectroscopy and mass spectrometry. Most mass spectrometry (MS) methods must be coupled to various forms of liquid chromatography (LC), gas chromatography (GC) or capillary electrophoresis (CE) to facilitate compound separation. Each method is typically able to identify or characterize 50-5000 different metabolites or metabolite “features” at a time, depending on the instrument or protocol being used. See Figure 2 for an illustration of the relationship between different analytical methods and their sensitivity. Currently it is not possible to analyze the entire range of metabolites by a single analytical method.
15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15("S")-HETE, and 15"S"-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15("S")-hydroperoxyeicosatetraenoic acid (15("S")-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15"(S)"-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5"S",15"S"-dihydroxy-eicosatetraenoic acid (5("S"),15("S")-diHETE), 5-oxo-15("S")-hydroxyeicosatetraenoic acid (5-oxo-15("S")-HETE, a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15("S")-HETE and 15("S")-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.
JWH-018 usage is readily detected in urine using "spice" screening immunoassays from several manufacturers focused on both the parent drug and its omega-hydroxy and carboxyl metabolites. JWH-018 will not be detected by older methods employed for detecting THC and other cannabis terpenoids. Determination of the parent drug in serum or its metabolites in urine has been accomplished by GC-MS or LC-MS. Serum JWH-018 concentrations are generally in the 1–10 μg/L range during the first few hours after recreational usage. The major urinary metabolite is a compound that is monohydroxylated on the omega minus one carbon atom of the alkyl side chain. A lesser metabolite monohydroxylated on the omega (terminal) position was present in the urine of 6 users of the drug at concentrations of 6–50 μg/L, primarily as a glucuronide conjugate.
An organic diet is an effective way to reduce exposure to the organophosphorus pesticides commonly used in agricultural production. Organophosphate metabolite levels rapidly drop, and for some metabolites, become undetectable in children's urine when an organic diet is consumed. This is speculative based on a short study of 23 children, in which only a few organophosphate compounds were potentially reduced, no effect was shown for the majority of them that were found in the samples.
In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.
Although these properties are interrelated, they are not interdependent. A metal hydride can be a thermodynamically a weak acid and a weak H donor; it could also be strong in one category but not the other or strong in both. The H strength of a hydride also known as its hydride donor ability or hydricity corresponds to the hydride's Lewis base strength. Not all hydrides are powerful Lewis bases. The base strength of hydrides vary as much as the pKa of protons. This hydricity can be measured by heterolytic cleaving hydrogen between a metal complex and base with a known pK then measuring the resulting equilibrium. This presupposes that the hydride doesn't heterolytically or homolytically react with itself to reform hydrogen. A complex would homolytically react with itself if the homolytic M-H bond is worth less than half of the homolytic H-H bond. Even if the homolytic bond strength above that threshold the complex is still susceptible to radical reaction pathways.
There are two major medications derived from methylphenidate's isomers: a racemic mixture of half d-threo-methylphenidate and half l-threo-methylphenidate called methylphenidate (Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called dexmethylphenidate (Focalin).
Organophosphates (also known as phosphate esters) are a class of organophosphorus compounds with the general structure O=P(OR). They can be considered as esters of phosphoric acid. Like most functional groups organophosphates occur in a diverse range of forms, with important examples including key biomolecules such as DNA, RNA and ATP, as well as many insecticides, herbicides, and nerve agents.
Any substance consisting of two or more different types of atoms (chemical elements) in a fixed stoichiometric proportion can be termed a "chemical compound"; the concept is most readily understood when considering pure chemical substances. It follows from their being composed of fixed proportions of two or more types of atoms that chemical compounds can be converted, via chemical reaction, into compounds or substances each having fewer atoms. The ratio of each element in the compound is expressed in a ratio in its chemical formula. A chemical formula is a way of expressing information about the proportions of atoms that constitute a particular chemical compound, using the standard abbreviations for the chemical elements, and subscripts to indicate the number of atoms involved. For example, water is composed of two hydrogen atoms bonded to one oxygen atom: the chemical formula is HO. In the case of non-stoichiometric compounds, the proportions may be reproducible with regard to their preparation, and give fixed proportions of their component elements, but proportions that are not integral [e.g., for palladium hydride, PdH (0.02 < x < 0.58)].
15-Lipoxygenase-1: Cells metabolize arachidonic acid with 15-lipoxygenase-1 (i.e., 15-LO-1, ALOX15) to form 15("S")-HpETE as a major product and 12("S")-hydroperoxy-5"Z",8"Z",10"E",15"Z"-eicosatetraenoic acid (12("S")-HpETE) and 14("S"),15("S")-"trans"-oxido-5"Z",8"Z",11"Z"-14,15-leukotriene A4 as minor products; 15("S")-HpETE and 12("S")-HpETE are rapidly converted to 15("S")-HETE and 12("S")-hydroxy-5"Z",8"Z",10"E",15"Z"-eicosatetraenoic acid (12("S")-hydroxyeicosatetraenoic acid), (i.e. 12("S")-HETE), respectively, or further metabolized through other enzyme pathways; 14("S"),15("S")-"trans"-oxido-5"Z",8"Z",11"Z"-14,15-leukotriene A is metabolized by 15-LO-1 to various isomers of 8,15("S")-dihydroxy-5"S",8"S","11Z",13"S"-eicosatetraenoic acids, e.g. 8,15(S)-LTB's.
A microbe is an organism that is microscopic.
A chemical formula is a way of expressing information about the proportions of atoms that constitute a particular chemical compound, using the standard abbreviations for the chemical elements, and subscripts to indicate the number of atoms involved. For example, water is composed of two hydrogen atoms bonded to one oxygen atom: the chemical formula is HO. Many chemical compounds have a unique numerical identifier assigned by the Chemical Abstracts Service (CAS): its CAS number.
Sometimes drugs are formulated in an inactive form that is designed to break down inside the body to form the active drug. These are called prodrugs. The reasons for this type of formulation may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better absorbed by the body or has superior pharmacokinetics (e.g., lisdexamphetamine).
Organisms typically cannot metabolize all types of carbohydrate to yield energy. Glucose is a nearly universal and accessible source of energy. Many organisms also have the ability to metabolize other monosaccharides and disaccharides but glucose is often metabolized first. In "Escherichia coli", for example, the lac operon will express enzymes for the digestion of lactose when it is present, but if both lactose and glucose are present the "lac" operon is repressed, resulting in the glucose being used first (see: Diauxie). Polysaccharides are also common sources of energy. Many organisms can easily break down starches into glucose; most organisms, however, cannot metabolize cellulose or other polysaccharides like chitin and arabinoxylans. These carbohydrate types can be metabolized by some bacteria and protists. Ruminants and termites, for example, use microorganisms to process cellulose. Even though these complex carbohydrates are not very digestible, they represent an important dietary element for humans, called dietary fiber. Fiber enhances digestion, among other benefits.
Amino acids are organic compounds containing amine (-NH) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.
The Nobel laureate, Bengt I. Samuelsson, and colleagues first described 5("S")-HETE in 1976 as a metabolite of arachidonic acid made by rabbit neutrophils. Biological activity was linked to it several years later when it was found to stimulate human neutrophil rises in cytosolic calcium, chemotaxis, and increases in their cell surface adhesiveness as indicated by their aggregation to each other. Since a previously discovered arachidonic acid metabolite made by neutrophils, leukotriene B4 (LTB), also stimulates human neutrophil calcium rises, chemotaxis, and auto-aggregation and is structurally similar to 5("S")-HETE in being a 5-("S")-hydroxy-eicosateraenoate, it was assumed that 5-("S")-HETE stimulated cells through the same cell surface receptors as those used by (LTB) viz., the leukotriene B4 receptors. However, further studies in neutrophils indicated that 5-("S")-HETE acts through a receptor distinct from that used by LTB as well as various other neutrophil stimuli. This 5("S")-HETE receptor is termed the oxoeicosanoid receptor 1 (abbreviated as (OXER1).
An artificial cell or minimal cell is an engineered particle that mimics one or many functions of a biological cell. The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such, nanoparticles, liposomes, polymersomes, microcapsules and a number of other particles have qualified as artificial cells. Micro-encapsulation allows for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. The main advantages of encapsulation include improved mimicry in the body, increased solubility of the cargo and decreased immune responses. Notably, artificial cells have been clinically successful in hemoperfusion.
Bis-choline tetrathiomolybdate (or tiomolibdate USAN, trade name Decuprate), is a salt of tetrathiomolybdate (TTM, MoS) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson's disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 30,000 worldwide have Wilson's disease, corresponding to approximately 15,000 individuals in the European Union and approximately 11,000 in the United States.
Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people both with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.
Metal hydroxides are also known as strong bases. Many common metal hydroxides are made up from hydroxide ions and the ion of the particular metal that it is made up of. Example: When NaOH (sodium hydroxide) is dissolved in water, it forms OH ions and Na ions. Metal hydroxides ionize completely when dissolved, so that is why they are known as strong bases. Their pH is above 7, labeling them as bases. Since ions conduct electricity, metal hydroxides carry electricity very well when they are dissolved.In soils, it is assumed that larger amounts of natural phenols are released from decomposing plant litter rather than from throughfall in any natural plant community. Decomposition of dead plant material causes complex organic compounds to be slowly oxidized (lignin-like humus) or to break down into simpler forms (sugars and amino sugars, aliphatic and phenolic organic acids), which are further transformed into microbial biomass (microbial humus) or are reorganized, and further oxidized, into humic assemblages (fulvic and humic acids), which bind to clay minerals and metal hydroxides.
Secondary metabolites are essentially low molecular weight compounds, sometimes having complex structures, that are not essential for the normal processes of growth, development, or reproduction. They function in processes as diverse as immunity, anti-herbivory, pollinator attraction, communication between plants, maintaining symbiotic associations with soil flora, or enhancing the rate of fertilization, and hence are significant from the evo-devo perspective. Secondary metabolites are structurally and functionally diverse, and it is estimated that hundreds of thousands of enzymes might be involved in the process of producing them, with about 15–25% of the genome coding for these enzymes, and every species having its unique arsenal of secondary metabolites. Many of these metabolites, such as salicylic acid are of medical significance to humans.
The MSEA web server is a freely available web server for performing metabolite set enrichment analysis on human or mammalian metabolomics data. The required input is either a list of compound names or compound names and concentrations. The output is a set of graphs and tables with embedded hyperlinks to the pertinent pathway images and descriptors. The Metabolite Set Enrichment Analysis offered by the web server is based on a curated library of more 5000 predefined metabolite sets covering various human metabolic pathways (nearly 100), hundreds of human disease states (in 3 different biofluids), human biofluid and tissue locations as well as human SNP-metabolite associations (4500 different SNP associations). MSEA also allows users to upload custom metabolite sets for more specialized analysis (such as non-mammalian MSEA work). Three different enrichment analyses are supported by the server: 1) overrepresentation analysis (ORA); 2) single sample profiling (SSP) and 3) quantitative enrichment analysis (QEA). ORA analysis only needs a list of compound names. SSP and QEA need both compound names and their concentrations. Workflows, examples and other screenshot tutorials on how to use the server are available on the MSEA website. The MSEA server also offers a number of other functions including the conversion between metabolite common names, synonyms, and major database identifiers.
Secondary metabolites are organic compounds produced by bacteria, fungi, or plants which are not directly involved in the normal growth, development, or reproduction of the organism. Unlike primary metabolites, absence of secondary metabolites does not result in immediate death, but rather in long-term impairment of the organism's survivability, fecundity, or aesthetics, or perhaps in no significant change at all. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavorings, pigments, and recreational drugs.
Similarly to DNA and proteins, metabolites are prone to damage, which can occur chemically or through enzyme promiscuity. Much less is known about metabolite damage than about DNA and protein damage, in part due to the huge variety and number of damage-prone metabolites.
Many metabolites are chemically reactive and unstable, and thus prone to chemical damage. In general, any reaction that occurs "in vitro" under physiological conditions can also occur "in vivo". Some metabolites are so reactive that their half-life in a cell is measured in minutes. For example, the glycolytic intermediate 1,3-bisphosphoglyceric acid has a half-life of 27 minutes "in vivo". Typical types of chemical damage reactions that can occur to metabolites are racemization, rearrangement, elimination, photodissociation, addition, and condensation.