Sandbox Reserved 921

This Sandbox is Reserved from Jan 06, 2014, through Aug 22, 2014 for use by the Biochemistry II class at the Butler University at Indianapolis, IN USA taught by R. Jeremy Johnson. This reservation includes Sandbox Reserved 911 through Sandbox Reserved 922.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert a 3D applet Jmol scene window. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

Fatty Acid Amide Hydrolase

Figure Legend

IntroductionIntroduction

[Fatty acid amid hydrolase]http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase (FAAH) is the primary catabolic enzyme for the degradation of fatty acid amides. FAAH is most commonly known for the degradation of anandamid[1], which is an endocannabinoid that activates the CB1 and CB2 cannabinoid receptors[2]. When CB1 and CB2 cannabinoid receptors are active the receptors affect appetite, sleep, and relief of pain. The ability to inhibit FAAH has been widely investigated for possible pain relief medication. A recent study on FAAH inhibitors combined an irreversible bond at Cys269 and a reversible bond at Ser241 of the active site. A humanized rat variant of FAAH was inhibited and the mice displayed an increase in endogenous brain levels of FAAH substrates for over six hours. This is the first step towards developing a long lasting pain relief medication by inhibiting FAAH.

spinqualitylabelsall models FAAH Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

FunctionFunction

The fatty acid amide hydrolase cleaves fatty acid amides at the carbon-oxygen double bond in the amide functional group. FAAH uses the active site a catalytic triad consisting of Ser241, Ser217, and Lys142 to degrade the lipids. The hydrogen bonding between the three amino acid residues allows for a partial negative charge at Ser241, which acts as a nucleophile in the enzymatic reaction. The Ser241 residue binds with the carbon in the amide group, cleaves the fatty acid amide, and is protonated by water. The inhibitor used covalently binds to Ser241 disrupting the catalytic triad active site and leaving the hydrolase inactive. Without the enzyme FAAH active, anandamide levels increase causing pain relief due to anandamide interacting with the CB1 and CB2 cannabinoid receptors.