Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acylethanolamine (NAE), including anandamide, in mammals in relation to neurotoxicity is discussed. Data on the characterization of the NAPE-forming N-acyltransferase, the NAPE-hydrolyzing phospholipase D, and the NAE-hydrolyzing amidase are reviewed. We suggest that NAPE and NAE, including anandamide, are formed in neurons in response to the high intracellular calcium concentrations that occur in injured neurons, e.g. due to glutamate excitotoxicity. NAPE may have functions of its own besides being a precursor for NAE. The formation of both of these lipids may serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes, or mediated by activation of cannabinoid receptors. This suggestion implies that NAPE and NAE may have pathophysiological roles in the brain. Whether these lipids also have physiological roles is uncertain.
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PMID:Formation of N-acyl-phosphatidylethanolamines and N-acetylethanolamines: proposed role in neurotoxicity. 958 43

The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described the acute actions of ethanol on AEA production and degradation. In the present study, we investigated the time course of the effects of the intraperitoneal administration of ethanol (4 g/kg of body mass) on the endogenous levels of AEA in central and peripheral tissues. Acute ethanol administration decreased AEA in the cerebellum, the hippocampus and the nucleus accumbens of the ventral striatum, as well as in plasma and adipose tissue. Parallel decreases of a second acylethanolamide, PEA (palmitoylethanolamide), were observed in the brain. Effects were observed 45-90 min after ethanol administration. In vivo studies revealed that AEA decreases were associated with a remarkable inhibition of the release of both anandamide and glutamate in the nucleus accumbens. There were no changes in the expression and enzymatic activity of the main enzyme that degrades AEA, the fatty acid amidohydrolase. Acute ethanol administration did not change either the activity of N-acyltransferase, the enzyme that catalyses the synthesis of the AEA precursor, or the expression of NAPE-PLD (N-acylphosphatidylethanolamine-hydrolysing phospholipase D), the enzyme that releases AEA from membrane phospholipid precursors. These results suggest that receptor-mediated release of acylethanolamide is inhibited by the acute administration of ethanol, and that this effect is not derived from increased fatty acid ethanolamide degradation.
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PMID:Regulation of brain anandamide by acute administration of ethanol. 1730 58

Fatty acyl ethanolamides represent a class of endogenous bioactive lipid molecules and are generally referred to as N-acylethanolamines (NAEs). NAEs include palmitoylethanolamide (anti-inflammatory and analgesic substance), oleoylethanolamide (anorexic substance), and anandamide (endocannabinoid). The endogenous levels of NAEs are mainly regulated by enzymes responsible for their biosynthesis and degradation. In mammalian tissues, the major biosynthetic pathway starts from glycerophospholipids and is composed of two enzyme reactions. The first step is N-acylation of ethanolamine phospholipids catalyzed by Ca(2+)-dependent N-acyltransferase and the second step is the release of NAEs from N-acylated ethanolamine phospholipids by N-acylphosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD). As for the degradation of NAEs, fatty acid amide hydrolase plays the central role. However, recent studies strongly suggest the involvement of other enzymes in the NAE metabolism. These enzymes include members of the HRAS-like suppressor family (also called phospholipase A/acyltransferase family), which were originally discovered as tumor suppressors but can function as Ca(2+)-independent NAPE-forming N-acyltransferases; multiple enzymes involved in the NAPE-PLD-independent multi-step pathways to generate NAE from NAPE, which came to light by the analysis of NAPE-PLD-deficient mice; and a lysosomal NAE-hydrolyzing acid amidase as a second NAE hydrolase. These newly recognized enzymes may become the targets for the development of new therapeutic drugs. Here, we focus on recent enzymological findings in this area.
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PMID:New players in the fatty acyl ethanolamide metabolism. 2474 63

This study aimed to investigate potential new target(s)/mechanism(s) for the palmitoylethanolamide (PEA) analogue, adelmidrol, and its role in an in vitro model of contact allergic dermatitis. Freshly isolated canine keratinocytes, human keratinocyte (HaCaT) cells and human embryonic kidney (HEK)-293 cells, wild-type or transfected with cDNA encoding for N-acylethanolamine-hydrolysing acid amidase (NAAA), were treated with adelmidrol or azelaic acid, and the concentrations of endocannabinoids (anandamide and 2-arachidonoylglycerol) and related mediators (PEA and oleoylethanolamide) were measured. The mRNA expression of PEA catabolic enzymes (NAAA and fatty acid amide hydrolase, FAAH), and biosynthetic enzymes (N-acyl phosphatidylethanolamine-specific phospholipase D, NAPE-PLD) and glycerophosphodiester phosphodiesterase 1, was also measured. Brain or HEK-293 cell membrane fractions were used to assess the ability of adelmidrol to inhibit FAAH and NAAA activity, respectively. HaCaT cells were stimulated with polyinosinic-polycytidylic acid and the release of the pro-inflammatory chemokine, monocyte chemotactic protein-2 (MCP-2), was measured in the presence of adelmidrol. Adelmidrol increased PEA concentrations in canine keratinocytes and in the other cellular systems studied. It did not inhibit the activity of PEA catabolic enzymes, although it reduced their mRNA expression in some cell types. Adelmidrol modulated the expression of PEA biosynthetic enzyme, NAPE-PLD, in HaCaT cells, and inhibited the release of the pro-inflammatory chemokine MCP-2 from stimulated HaCaT cells. This study demonstrates for the first time an 'entourage effect' of adelmidrol on PEA concentrations in keratinocytes and suggests that this effect might mediate, at least in part, the anti-inflammatory effects of this compound in veterinary practice.
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PMID:Adelmidrol increases the endogenous concentrations of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis. 2663 24