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

Incubation of rat hepatocytes with anandamide (arachidonoylethanolamide) inhibited acetyl-CoA carboxylase activity and fatty acid synthesis de novo without affecting fatty acid synthase. This was concomitant to a decrease in the intracellular levels of malonyl-CoA. Likewise, anandamide depressed both cholesterol synthesis de novo and the incorporation of exogenous palmitate into triacylglycerols and phospholipids. On the other hand, anandamide stimulated in parallel both carnitine palmitoyltransferase I activity and ketogenesis from palmitate, though ketogenesis from octanoate was unaffected. The effects of anandamide on hepatic fatty acid synthesis and oxidation were: (a) mimicked by arachidonic acid, a product of anandamide breakdown by anandamide amidase; (b) prevented by phenylmethylsulfonyl fluoride, an inhibitor of anandamide amidase; and (c) not affected by bisindolylmaleimide, a specific inhibitor of protein kinase C. Furthermore, delta 9-tetrahydrocannabinol had no effect on any of the parameters determined, ruling out the possibility that the effects of anandamide on hepatic fatty acid metabolism are mediated by the peripheral cannabinoid receptor. The results thus indicate that anandamide might function as a carrier of arachidonic acid in the modulation of hepatic fatty metabolism.
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PMID:Effects of anandamide on hepatic fatty acid metabolism. 757 52

Recent evidence has demonstrated that arachidonylethanolamide ("anandamide", AEA), the major endogenous ligand of CB1 receptors, inhibits motor behavior in rats, as does (-)delta 9-tetrahydrocannabinol (THC), the prototypical tricyclic cannabinoid derived from Cannabis sativa preparations. However, its effects were of shorter duration, as compared to THC, likely due to its rapid breakdown by an amidase activity. The present work has been designed to examine the motor effects of AM356(R-methanandamide), an analog of AEA that possesses higher metabolic stability to amidase hydrolysis. We have studied the dose-response and time-course effects of R-methanandamide, i.p. administered, on ambulatory activity, frequency of stereotypy and time spent in inactivity measured in an open-field test. Results were as follows. R-Methanandamide, as THC and AEA, inhibited motor behavior. Thus, it decreased ambulation and stereotypy and increased the time spent in inactivity, usually in a dose-related manner, 10 min after administration. However, the motor deficit caused by the highest dose of R-methanandamide was usually more pronounced than that caused by a similar dose of AEA. These inhibitory effects persisted 30 min after the administration of R-methanandamide, as occurred with AEA and THC. Interestingly, at 60 min after administration, the effects of AEA disappeared, likely because of its breakdown to arachidonic acid and ethanolamine, but this did not occur with R-methanandamide whose effects persisted even until 180 min after treatment as occurred with THC. In summary, R-methanandamide inhibits motor behavior in a manner (its effects were persistent) that resembles the effects of THC rather than the effects of AEA (its effects were of rapid onset but shorter duration). This fact supports the use of R-methanandamide as a valuable tool for studying the physiological roles of the anandamidergic system.
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PMID:Extrapyramidal effects of methanandamide, an analog of anandamide, the endogenous CB1 receptor ligand. 861 78

Mouse brain microsomes contain an amidase that catalyzes the hydrolysis of N-arachidonylethanolamide to arachidonic acid and ethanolamine. The enzymatic activity is dependent on the protein concentration of the microsomes and observed over a wide range of pH, 7.4 to 9.5. Kinetic analysis indicated that K(m) (microM) and Vmax (nmol/min/mg protein) were 17.7 +/- 4.1 and 1.81 +/- 0.32, respectively. Cannabidiol (CBD), cannabinol (CBN) and delta 9-tetrahydrocannabinol (delta 9-THC) significantly inhibited the hydrolysis of the amide by mouse brain microsomes. At a concentration of 160 microM, the inhibitory potency decreased in the following order, CBD (66%) > CBN (46%) > delta 9-THC (31%).
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PMID:Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids. 887 30