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 been 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 et 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 in 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 peptidyl-glycine alpha-amidating enzyme would lead to the biosynthesis of fatty acid amides.
Merkler
D J
DJ
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, USA.
Merkler
K A
KA
Stern
W
W
Fleming
F F
FF
D000217:Acyltransferases / Q000378:metabolism*; D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005227:Fatty Acids / Q000096:biosynthesis* / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009227:Myristic Acids / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D000577:Amides; D005227:Fatty Acids; D009097:Multienzyme Complexes; D009227:Myristic Acids; D009842:Oligopeptides; C057393:N-myristoylglycine; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D000217:Acyltransferases; C020680:glycine acyltransferase; D005998:Glycine