Fatty Acid Amide Biosynthesis: A Possible New Role for Peptidylglycine α-Amidating Enzyme and Acyl-Coenzyme A:GlycineN-Acyltransferase

Fatty acid primary amides have recently been recognized as mammalian hormones [Cravattet al.(1995)Science268, 1506–1509]. The route to their biosynthesis is unknown. Many mammalian peptide hormones also possess a C-terminal α-amide moiety that arises from the posttranslational oxidative cleavage of a C-terminal glycine-extended precursor. The enzyme that catalyzes this reaction is peptidylglycine α-amidating enzyme, which is known to preferentially amidate peptide substrates containing a penultimate, hydrophobic amino acid [Tamburiniet al.(1990)Int. J. Pept. Protein Res.35, 153–156]. We show thatN-myristoylglycine is a substrate for peptidylglycine α-amidating enzyme with a (V/K)appthat is 55 ± 4% of the value measured for D-Tyr-Val-Gly.N-Fatty acylglycines are enzymatically produced in mammals from fatty acyl-coenzyme A (CoAs) and glycine by acyl-CoA:glycineN-acyltransferase. The sequential actions of acyl-CoA:glycineN-acyltransferase and peptidylglycine α-amidating enzyme would lead to the biosynthesis of fatty acid amides.