Fatty acid amides (FAAs) are amides formed from a fatty acid and an amine. In nature, many FAAs have ethanolamine as the amine component. Also known as N-acylethanolamines, they contain the functionality RC(O)N(H)CH2CH2OH. A well known example is anandamide. Other fatty acid amides are fatty acid primary amides (FAPAs). They contain the functionality RC(O)NH2). Oleamide is an example of this class of FAPAs. [1]
FAAs play a role in intracellular signalling. The signalling is controlled in part by fatty acid amide hydrolases, which convert the amide to the parent fatty acid. One example of signaling is induced by the binding of anandamide to the cannabinoid receptors. [1]
Aliphatic amides can be found in Zanthoxylum species found in Nigeria. [2]
Anandamide (ANA), also known as N-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid receptors, the same receptors that the psychoactive compound THC in cannabis acts on. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. The name 'anandamide' is taken from the Sanskrit word ananda, which means "joy, bliss, delight", plus amide.
Benjamin Franklin Cravatt III is a professor in the Department of Chemistry at The Scripps Research Institute in La Jolla, California. Considered a co-inventor of activity based proteomics and a substantial contributor to research on the endocannabinoid system, he is a prominent figure in the nascent field of chemical biology. Cravatt was elected to the National Academy of Sciences in 2014, and the American Academy of Arts and Sciences in 2016. He is Gilula Chair of Chemical Biology, a Cope Scholar, and a Searle Scholar.
URB597 (KDS-4103) is a relatively selective and irreversible inhibitor of the enzyme fatty acid amide hydrolase (FAAH). FAAH is the primary degradatory enzyme for the endocannabinoid anandamide and, as such, inhibition of FAAH leads to an accumulation of anandamide in the CNS and periphery where it activates cannabinoid receptors. URB597 has been found to elevate anandamide levels and have activity against neuropathic pain in a mouse model.
Monoacylglycerol lipase is an enzyme that, in humans, is encoded by the MGLL gene. MAGL is a 33-kDa, membrane-associated member of the serine hydrolase superfamily and contains the classical GXSXG consensus sequence common to most serine hydrolases. The catalytic triad has been identified as Ser122, His269, and Asp239.
Fatty acid amide hydrolase or FAAH is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene FAAH.
2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present at relatively high levels in the central nervous system, with cannabinoid neuromodulatory effects. It has been found in maternal bovine and human milk. The chemical was first described in 1994-1995, although it had been discovered some time before that. The activities of phospholipase C (PLC) and diacylglycerol lipase (DAGL) mediate its formation. 2-AG is synthesized from arachidonic acid-containing diacylglycerol (DAG).
In chemistry, the term substrate is highly context-dependent. Broadly speaking, it can refer either to a chemical species being observed in a chemical reaction, or to a surface on which other chemical reactions or microscopy are performed.
AM404, also known as N-arachidonoylaminophenol, is an active metabolite of paracetamol (acetaminophen), responsible for all or part of its analgesic action and anticonvulsant effects. Chemically, it is the amide formed from 4-aminophenol and arachidonic acid.
Oleamide is an organic compound with the formula CH3(CH2)7CH=CH(CH2)7CONH2(. It is the amide derived from the fatty acid oleic acid. It is a colorless waxy solid and occurs in nature. Sometimes labeled as a fatty acid primary amide (FAPA), it is biosynthesized from N-oleoylglycine.
In enzymology, an amidase is an enzyme that catalyzes the hydrolysis of an amide:
JZL184 is an irreversible inhibitor for monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG). It displays high selectivity for MAGL over other brain serine hydrolases, including the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH), thereby making it a useful tool for studying the effects of endogenous 2-AG signaling, in vivo. Administration of JZL184 to mice was reported to cause dramatic elevation of brain 2-AG leading to several cannabinoid-related behavioral effects.
N-Acylphosphatidylethanolamines (NAPEs) are hormones released by the small intestine into the bloodstream when it processes fat. NAPEs travel to the hypothalamus in the brain and suppress appetite. This mechanism could be relevant for treating obesity.
N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) is an enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE). This is a major part of the process that converts ordinary lipids into chemical signals like anandamide and oleoylethanolamine. In humans, the NAPE-PLD protein is encoded by the NAPEPLD gene.
JZL195 is a potent inhibitor of both fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the primary enzymes responsible for degrading the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively.
LY-2183240 is a drug which acts both as a potent inhibitor of the reuptake of the endocannabinoid anandamide and as an inhibitor of fatty acid amide hydrolase (FAAH), the primary enzyme responsible for degrading anandamide. This leads to markedly elevated anandamide levels in the brain, and LY-2183240 has been shown to produce both analgesic and anxiolytic effects in animal models. While LY-2183240 is a potent inhibitor of FAAH, it has relatively poor selectivity and also inhibits several other enzyme side targets. Consequently, it was never developed for clinical use, though it remains widely used in research, and has also been sold as a designer drug.
IDFP is an organophosphorus compound related to the nerve agent sarin.
The endocannabinoid transporters (eCBTs) are transport proteins for the endocannabinoids. Most neurotransmitters are water-soluble and require transmembrane proteins to transport them across the cell membrane. The endocannabinoids on the other hand, are non-charged lipids that readily cross lipid membranes. However, since the endocannabinoids are water immiscible, protein transporters have been described that act as carriers to solubilize and transport the endocannabinoids through the aqueous cytoplasm. These include the heat shock proteins (Hsp70s) and fatty acid-binding proteins for anandamide (FABPs). FABPs such as FABP1, FABP3, FABP5, and FABP7 have been shown to bind endocannabinoids. FABP inhibitors attenuate the breakdown of anandamide by the enzyme fatty acid amide hydrolase (FAAH) in cell culture. One of these inhibitors (SB-FI-26), isolated from a virtual library of a million compounds, belongs to a class of compounds that act as an anti-nociceptive agent with mild anti-inflammatory activity in mice. These truxillic acids and their derivatives have been known to have anti-inflammatory and anti-nociceptive effects in mice and are active components of a Chinese herbal medicine used to treat rheumatism and pain in human. The blockade of anandamide transport may, at least in part, be the mechanism through which these compounds exert their anti-nociceptive effects.
N-acylethanolamine acid amide hydrolase (NAAA) EC 3.5.1.- is a member of the choloylglycine hydrolase family, a subset of the N-terminal nucleophile hydrolase superfamily. NAAA has a molecular weight of 31 kDa. The activation and inhibition of its catalytic site is of medical interest as a potential treatment for obesity and chronic pain. While it was discovered within the last decade, its structural similarity to the more familiar acid ceramidase (AC) and functional similarity to fatty acid amide hydrolase (FAAH) allow it to be studied extensively.
PF-3845 is a selective inhibitor of fatty acid amide hydrolase. It results in increased levels of anandamide and results in cannabinoid receptor-based effects. It has anti-inflammatory action in mice colitis models. Antidiarrheal and antinociceptive effects were also seen in mouse models of pain.
Fatty acid amide hydrolase 2 or FAAH2 is a member of the serine hydrolase family of enzymes.
