Peptidylglycine

Peptidylglycine is a term used in biochemistry to describe a peptide that terminates with a glycine residue and serves as the substrate for C-terminal amidation. In the maturation of many peptide hormones and neuropeptides, the terminal glycine is used as the donor of the amide nitrogen to form a C-terminal amide on the preceding amino acid; the glycine residue is released during this modification.

The enzymatic conversion is carried out by peptidylglycine alpha-amidating monooxygenase (PAM), a bifunctional enzyme with two domain activities: peptidylglycine alpha-hydroxylase (PHM) and peptidylglycine alpha-hydroxyglycine amidating lyase (PAL). PAM catalyzes an oxidative reaction that uses oxygen and reducing equivalents (and copper/ascorbate cofactors) to convert the peptidylglycine substrate through a hydroxyglycine intermediate to the amidated peptide, with the glycine moiety ultimately released as a byproduct such as glyoxylate. The overall result is a mature peptide bearing a C-terminal amide.

Significance: C-terminal amidation is a widespread post-translational modification essential for the activity, stability, and receptor interactions of many peptide hormones and neuropeptides. Accordingly, peptidylglycine substrates and PAM activity are important in endocrinology and neuroscience. Defects in amidation pathways can impair peptide function, while PAM expression and activity have been investigated in various physiological and pathological contexts.