Fatty acid amide biosynthesis: A possible new role for peptidylglycine alpha-amidating enzyme and acyl-coenzyme A:glycine N-acyltransferase

Fatty acid primary amides have recently bees recognized as mammalian hormones [Cravatt et al. (1995) Science 268, 1506-1509], The route to their biosynthesis is unknown. Many mammalian peptide hormones also possess a C-terminal alpha-amide moiety that arises from the posttranslational oxidative cleavage of a C-terminal glycine-extended precursor, The enzyme that catalyzes this reaction is peptidylglycine alpha-amidating enzyme, which is known to preferentially amidate peptide substrates containing a penultimate, hydrophobic amino acid [Tamburini Bt al, (1990) Int. J. Pept. Protein Res, 35, 153-156], We show that N-myristoylglycine is a substrate for peptidylglycine alpha-amidating enzyme with a (V/K)(app) that is 55 +/- 4% of the Value measured for D-Tyr-Val-Gly, N-Fatty acylglycines are enzymatically produced iu mammals from fatty acyl-coenzyme A (CoAs) and glycine by acyl-CoA:glycine N-acyltransferase. The sequential actions of acyl-CoA:glycine N-acyltransferase and peptidylglycine alpha-amidating enzyme would lead to the biosynthesis of fatty acid amides. (C) 1996 Academic Press, Inc.