Names | |
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IUPAC name (2S)-Amino[(5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl]ethanoic acid | |
Other names Antibiotic AT 125 | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C5H7ClN2O3 | |
Molar mass | 178.574 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Acivicin is an analog of glutamine. It is an inhibitor of gamma-glutamyl transferase.
It is a fermentation product of Streptomyces sviceus . [1] It interferes with glutamate metabolism and inhibits glutamate dependent synthesis of enzymes, and is thereby potentially helpful in treatment of solid tumors. [2]
After its discovery in 1972, acivicin was studied as an anti-cancer agent, but trials were unsuccessful due to toxicity. [3]
An in vitro study showed that Acivicin at a concentration of 5 μM Acivicin inhibited by 78% the growth of human pancreatic carcinoma cells (MIA PaCa-2) after 72 hours in continuous culture. It was also found that acivicin at a concentration of 450 μM irreversibly inactivated MIA PaCa-2 γ-glutamyl transpeptidase (10 nmol/min/106 cells) with an inactivation half-life of 80 minutes. [1]
Phase I dose escalating studies conducted in 23 cancer patients administered acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids showed reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion and decreased mental status.
α-Ketoglutaric acid is a keto acid.
Glutamic acid is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons.
Glutamine is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG.
γ-Aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
Gamma-glutamyltransferase is a transferase that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione to an acceptor that may be an amino acid, a peptide or water. GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione as well as drug and xenobiotic detoxification. Other lines of evidence indicate that GGT can also exert a pro-oxidant role, with regulatory effects at various levels in cellular signal transduction and cellular pathophysiology. This transferase is found in many tissues, the most notable one being the liver, and has significance in medicine as a diagnostic marker.
Glutamate dehydrogenase is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typically, the α-ketoglutarate to glutamate reaction does not occur in mammals, as glutamate dehydrogenase equilibrium favours the production of ammonia and α-ketoglutarate. Glutamate dehydrogenase also has a very low affinity for ammonia, and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed. However, in brain, the NAD+/NADH ratio in brain mitochondria encourages oxidative deamination. In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases. In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections. They are more nutritionally valuable.
Glutamine synthetase (GS) is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine:
The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
Azaserine is a naturally occurring serine derivative diazo compound with antineoplastic and antibiotic properties deriving from its action as a purinergic antagonist and structural similarity to glutamine. Azaserine acts by competitively inhibiting glutamine amidotransferase, a key enzyme responsible for glutamine metabolism.
Glutaminase is an amidohydrolase enzyme that generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Glutaminase has an important role in glial cells.
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:
Glutaminolysis (glutamine + -lysis) is a series of biochemical reactions by which the amino acid glutamine is lysed to glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate.
γ-L-Glutamyl-L-cysteine, also known as γ-glutamylcysteine (GGC), is a dipeptide found in animals, plants, fungi, some bacteria, and archaea. It has a relatively unusual γ-bond between the constituent amino acids, L-glutamic acid and L-cysteine and is a key intermediate in the γ-glutamyl cycle first described by Meister in the 1970s. It is the most immediate precursor to the antioxidant glutathione.
Arenobufagin is a cardiotoxic bufanolide steroid secreted by the Argentine toad Bufo arenarum. It has effects similar to digitalis, blocking the Na+/K+ pump in heart tissue.
6-Diazo-5-oxo-L-norleucine (DON) is a glutamine antagonist, which was isolated originally from Streptomyces in a sample of Peruvian soil. This diazo compound is biosynthesized from lysine by three enzymes in bacteria. It is one of the most famous non-proteinogenic amino acid and was characterized in 1956 by Henry W Dion et al., who suggested a possible use in cancer therapy. This antitumoral efficacy was confirmed in different animal models. DON was tested as chemotherapeutic agent in different clinical studies, but was never approved. In 2019, DON was shown to kill tumor cells while reversing disease symptoms and improve overall survival in late-stage experimental glioblastoma in mice, when combined with calorie-restricted ketogenic diet.
Gambogic acid is a xanthonoid that is derived from the brownish or orange resin from Garcinia hanburyi. Garcinia hanburyi is a small to medium-sized evergreen tree with smooth grey bark. It is native to Cambodia, southern Vietnam, and Thailand and has been successfully introduced in Singapore.
Cynaropicrin is a sesquiterpene lactone of the guaianolide type found mainly in leaves of artichoke plants. It is one of the compounds that gives the artichoke its characteristic bitterness. It is found in artichoke leaves with an abundance of approximately 87 g/kg, but can hardly be found in other parts of the plant. Cynaropicrin makes up about 0.7% of leaf extracts of the artichoke. It exhibits a large diversity of bioactivities and shows properties such as anti-inflammatory, antifeedant and activation of bitter sensory receptors, but has not yet been used in medicine. Despite its pharmacologically beneficial properties, it can be toxic in higher doses. The compound has attracted attention in recent years as a potential anticancer drug.
Immunomodulatory imide drugs (IMiDs) are a class of immunomodulatory drugs containing an imide group. The IMiD class includes thalidomide and its analogues. These drugs may also be referred to as 'Cereblon modulators'. Cereblon (CRBN) is the protein targeted by this class of drugs.
Crotoxin (CTX) is the main toxic compound in the snake venom of the South American rattlesnake, Crotalus durissus terrificus. Crotoxin is a heterodimeric beta-neurotoxin, composed of an acidic, non-toxic and non-enzymatic subunit (CA), and a basic, weakly toxic, phospholipase A2 protein (CB). This neurotoxin causes paralysis by both pre- and postsynaptic blocking of acetylcholine signalling.