Navigation Links
Study shows enzyme builds neurotransmitters via newly discovered pathway

The study, which was directed by Scripps Research Professor Benjamin Cravatt, Ph.D., is being published in the September 8 issue of The Journal of Biological Chemistry.

The new study describes a pathway-different than the one previously suggested-for the biosynthesis of neurotransmitter lipids, N-acyl ethanolamines (NAEs), which include the endogenous cannabinoid ("endocannabinoid") anandamide. The high activity of the enzyme a/b hydrolase4 (Abh4) in areas such as the central nervous system suggests that the pathway makes a "potentially major contribution" to endocannabinoid signaling.

Endocannabinoids are naturally produced substances similar to the active ingredient D9-tetrahydrocannabinol (THC) in marijuana. Cannabinoid receptors were first discovered in 1988; the first endocannabinoid, anandamide, which shares some of the pharmacologic properties of THC, was identified in 1992.

Other research has shown that the endogenous cannabinoid system helps control food intake, among other critical processes, by acting on cannabinoid receptors in the central nervous system. The system drives consumption of fat and calorie-rich foods and the amount of fat stored or expended and plays a significant role in energy homeostasis.

"At least one cannabinoid receptor antagonist is on the verge of approval for the treatment of obesity-metabolic disorders," said Cravatt. "Enzymes involved in endocannabinoid biosynthesis, such as the one highlighted in our study, can be viewed as complementary drug targets. One potential advantage of this approach is that it may prove more selective than a receptor antagonist. By inhibiting enzymes such as Abh4, we may be able to disrupt the activity of a single class of endocannabinoids, rather than all of them."

In the new study, the researchers provide biochemical evidence of an alternative pathway for NAE biosynthesis in vivo and demonstrate that these new routes are especially important for the creation o f a number of NAEs, including anandamide. The researchers also isolated and identified the enzyme Abh4 by combining traditional protein purification and functional proteomic technologies, concluding that Abh4 "displayed multiple properties" that would be expected of an enzyme involved in NAE biosynthesis.

However, the authors of the study noted, the unique contribution that this Abh4-mediated route makes to the production of NAEs in vivo is yet to be determined and will require "the generation of genetic or pharmacological tools that selectively [interrupt] this pathway."

"The continued pursuit of additional enzymes involved in NAE biosynthesis should further enrich our understanding of the complex metabolic network that supports the endocannabinoid/NAE system in vivo," Cravatt said. "From a therapeutic perspective, any of these enzymes could represent an attractive drug target for a range of human disorders in which disruption of endocannabinoid signaling by cannabinoid receptor antagonists has proven beneficial."


Source:Scripps Research Institute

Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works
Post Your Comments:

(Date:11/4/2015)... --> --> ... Transparency Market Research "Home Security Solutions Market - Global Industry ... 2022", the global home security solutions market is expected to reach ... market is estimated to expand at a CAGR of ... Rising security needs among customers at homes, the emergence ...
(Date:10/29/2015)... , Oct. 29, 2015   MedNet Solutions ... the entire spectrum of clinical research, is pleased to ... High Tech Association (MHTA) as one of only three ... the "Software – Small and Growing" category. The Tekne Awards ... who have shown superior technology innovation and leadership. ...
(Date:10/29/2015)... RESTON, Va. , Oct. 29, 2015 ... announced today that it has released a new version ... Daon customers in North America ... gains. IdentityX v4.0 also includes a FIDO UAF ... customers are already preparing to activate FIDO features. These ...
Breaking Biology News(10 mins):
(Date:11/26/2015)... 26, 2015 ... Accutest Research Laboratories, a leading independent ... (CRO), has formed a strategic partnership ... Temple Health for joint work on ... ) , --> ...
(Date:11/25/2015)... November 25, 2015 Studies reveal ... human plaque and pave the way for more effective treatment ... cats     --> ... diagnosed health problems in cats, yet relatively little was understood ... collaborative studies have been conducted by researchers from the WALTHAM ...
(Date:11/25/2015)... DIEGO , Nov. 25, 2015 Orexigen® ... management will participate in a fireside chat discussion at ... New York . The discussion is scheduled ... .  A replay will be ... Media Contact:McDavid Stilwell  , Julie NormartVP, Corporate Communications ...
(Date:11/24/2015)... Cepheid (NASDAQ: CPHD ) today announced ... conference, and invited investors to participate via webcast. ... December 1, 2015 at 11.00 a.m. Eastern Time ... December 1, 2015 at 11.00 a.m. Eastern Time ... York, NY      Tuesday, December 1, 2015 at ...
Breaking Biology Technology: