Peptidylglycine alpha-amidating monooxygenase (PAM) (PAM)

Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme essential for the activation of over half of all known neuropeptides and peptide hormones, including oxytocin, vasopressin, and gastrin (UniProt P19021). The enzyme consists of two distinct catalytic domains: peptidylglycine alpha-hydroxylating monooxygenase (PHM), which is copper- and ascorbate-dependent, and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) (PubMed 11062370). PHM catalyzes the hydroxylation of the C-terminal glycine of pro-peptides, while PAL catalyzes the cleavage of the N-C bond to produce the active amidated peptide and glyoxylate. Because amidation is often a prerequisite for high-affinity receptor binding and biological activity, PAM serves as a critical regulator of endocrine and neurobiological signaling (PubMed 25663104). In disease contexts, PAM is frequently overexpressed in neuroendocrine tumors and has been implicated in cardiovascular regulation and psychiatric disorders. Therapeutic strategies targeting PAM often involve small-molecule inhibitors that compete with peptidylglycine substrates or chelate the essential copper cofactors required for PHM activity (PubMed 8262902).

Other names

Peptidylglycine alpha-hydroxylating monooxygenasePeptidyl-alpha-hydroxyglycine alpha-amidating lyasePHMPAL

Inhibition of copper-dependent hydroxylation (PHM) or lyase activity (PAL) to prevent the conversion of pro-peptides into bioactive amidated forms (PubMed 11062370)