Arachidonoyl ethanolamide-[1,2-14C] as a substrate for anandamide amidase

Omeir, Romelda; Chin, Suzette A.; Hong, Yang; Ahern, David G.; Deutsch, Dale G.

doi:10.1016/0024-3205(95)00181-5

Cited by 88 publications

(48 citation statements)

References 13 publications

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“…First, the pH profile of [ 3 H]-PEA hydrolysis parallels the pH profile described for [ 3 H]-AEA hydrolysis by FAAH, both of which reach optimal activity at pH 8-9 (Omeir et al 1995;Ueda et al 1995). Second, MAFP and URB597 inhibit [ 3 H]-PEA hydrolysis with IC 50 values corresponding to those reported for recombinant FAAH .…”

Section: Discussionsupporting

confidence: 55%

Microglia produce and hydrolyze palmitoylethanolamide

Muccioli

Stella

2008

Neuropharmacology

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Microglial cell activation and migration play an important role in neuroinflammation propagation. While it is known that the lipid transmitter palmitoylethanolamide (PEA) regulates microglial migration by interacting with a cannabinoid-like receptor, the production and inactivation of this lipid by microglia has never been addressed directly. Here we show that the mouse microglial cell line BV-2 produces and hydrolyzes PEA. The carbamate compound URB602 inhibits PEA hydrolysis in BV-2 cell homogenates and increases PEA levels in intact cells, whereas the FAAH inhibitor URB597 and serine-hydrolase inhibitor MAFP do not affect PEA levels in intact cells. This unique pharmacological profile of inhibitors on PEA hydrolysis suggests the involvement of a previously undescribed enzyme that degrades PEA. This enzyme expressed by microglia constitutes a promising target for controlling the propagation of neuroinflammation.

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Section: Discussionsupporting

confidence: 55%

Microglia produce and hydrolyze palmitoylethanolamide

Muccioli

Stella

2008

Neuropharmacology

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“…This suggests that in vitro activities, employing high substrate concentrations, do not reveal the true catabolic capacities of NAE-inactivating enzymes in cells. The elevated activity of FAAH-2 in intact cells is supported by its low K m values for AEA and PEA, which are severalfold lower than those reported for FAAH (25,26). This suggests higher enzymatic activity at physiological substrate concentrations (i.e.…”

Section: Discussionmentioning

confidence: 86%

Lipid Droplets Are Novel Sites of N-Acylethanolamine Inactivation by Fatty Acid Amide Hydrolase-2

Kaczocha

Glaser

Chae

et al. 2010

Journal of Biological Chemistry

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Anandamide (AEA) and other bioactive N-acylethanolamines (NAEs) are primarily inactivated by the enzyme fatty acid amide hydrolase (FAAH). Recently, FAAH-2 was discovered in humans, suggesting an additional enzyme can mediate NAE inactivation in higher mammals. Here, we performed a biochemical characterization of FAAH-2 and explored its capacity to hydrolyze NAEs in cells. In homogenate activity assays, FAAH-2 hydrolyzed AEA and palmitoylethanolamide (PEA) with activities ϳ6 and ϳ20% those of FAAH, respectively. In contrast, FAAH-2 hydrolyzed AEA and PEA in intact cells with rates ϳ30 -40% those of FAAH, highlighting a potentially greater contribution toward NAE catabolism in vivo than previously appreciated. In contrast to endoplasmic reticulum-localized FAAH, immunofluorescence revealed FAAH-2 was localized on lipid droplets. Supporting this distribution pattern, the putative N-terminal hydrophobic region of FAAH-2 was identified as a functional lipid droplet localization sequence. Lipid droplet localization was essential for FAAH-2 activity as chimeras excluded from lipid droplets lacked activity and/or were poorly expressed. Lipid droplets represent novel sites of NAE inactivation. Therefore, we examined substrate delivery to these organelles. AEA was readily trafficked to lipid droplets, confirming that lipid droplets constitute functional sites of NAE inactivation. Collectively, these results establish FAAH-2 as a bone fide NAE-catabolizing enzyme and suggest that NAE inactivation is spatially separated in cells of higher mammals.

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“…One expectation is that the molecules under consideration be closely linked to a mechanism for their expedient inactivation. The fatty acid amides appear to meet this requirement as membrane-bound enzymatic activities from brain tissue have repeatedly been observed to hydrolyze fatty acid amides to their corresponding acids (2,(17)(18)(19)(20)(21). A matter of some interest has concerned whether a single enzyme could account for the degradation of multiple fatty acid amides, in particular both oleamide and anandamide (22).…”

mentioning

confidence: 99%

Molecular characterization of human and mouse fatty acid amide hydrolases

Giang

Cravatt

1997

Proc. Natl. Acad. Sci. U.S.A.

398

294

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Recently, we reported the isolation, cloning, and expression of a rat enzyme, fatty acid amide hydrolase (FAAH), that degrades bioactive fatty acid amides like oleamide and anandamide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Here, we report the molecular characterization of both a mouse and a human FAAH and compare these enzymes to the rat FAAH. The enzymes are well conserved in primary structure, with the mouse and rat FAAHs sharing 91% amino acid identity and the human FAAH sharing 82% and 84% identity with the rat FAAH and mouse FAAH, respectively. In addition, the expressed human and rat FAAHs behave biochemically as membrane proteins of comparable molecular size and show similar, but distinguishable, enzymological properties. The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid amides in mammalian biology.

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Arachidonoyl ethanolamide-[1,2-14C] as a substrate for anandamide amidase

Cited by 88 publications

References 13 publications

Microglia produce and hydrolyze palmitoylethanolamide

Microglia produce and hydrolyze palmitoylethanolamide

Lipid Droplets Are Novel Sites of N-Acylethanolamine Inactivation by Fatty Acid Amide Hydrolase-2

Molecular characterization of human and mouse fatty acid amide hydrolases

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