Biosynthesis of Long-chain Fatty Acid Amides
Doctor of Philosophy (Ph.D.)
Degree Granting Department
David J. Merkler, Ph.D.
Abdul Malik, Ph.D.
Sandy Westerheide, Ph.D.
Meera Nanjundan, Ph.D.
Jianfeng Cai, Ph.D.
Drosophila melanogaster, glycine N-acyltransferase, N-acylglycine, N-acylserotonin, siRNA
The vast variety of long-chain fatty acid amides identified in biological systems is intriguing. The general structure of a fatty acid amide is R-CO-NH-X, where R is an alkyl group and X is derived from an immense variety of biogenic amines. Although structurally simple, the bioactivities of these molecules as signaling lipids are very diverse and have just recently begun to emerge in the literature. Interest in the long-chain fatty acid amides dramatically increased following the identification and characterization of one specific N-acylethanolamine, N-arachidonoylethanolamine (anandamide), as the endogenous ligand for the cannabinoid receptors in the mammalian brain. Since this discovery, the details of N-acylethanolamine metabolism have been elucidated. However, a lesser extent of progress has been made in the last twenty years to identify and study the non-N-acylethanolamine long-chain fatty acid amides. The focus of this dissertation is the elucidation of the biosynthetic pathways for long-chain fatty acid amides, including N-acylglycines, primary fatty acid amides, N-acylarylalkylamides, and N-acylethanolamines. The details of long-chain fatty acid amide metabolism will lead to the determination of possible therapeutic targets. We identified mammalian glycine N-acyltransferase like 3 as the enzyme that catalyzes the formation of long-chain N-acylglycines in mouse N18TG2 neuoblastoma cells, identified and quantified a panel of long-chain fatty acid amides in Drosophila melanogaster extracts by LC/QTOF-MS, established Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism, and identified arylalkylamine N-acyltransferase like 2 as the enzyme that catalyzes the formation of long-chain N-acylserotonins and N-acyldopamines in Drosophila melanogaster.
Scholar Commons Citation
Jeffries, Kristen A., "Biosynthesis of Long-chain Fatty Acid Amides" (2015). Graduate Theses and Dissertations.