Figure 2. Schematic representation of a secretory vesicle containing progastrin and processing enzymes indicating the major steps and requirements for processing.

Internal pH is approximately 5·5 due to the activity of the vacuolar proton pump (vH⁺-ATPase), but proton extrusion via vesicular monoamine transporters (VMAT) may raise intragranular pH and inhibit cleavage. Biogenic amines transported by VMATs are generated from their precursors by aromatic amino acid decarboxylase (AADC). The bifunctional enzyme peptidyl α-amidating mono-oxygenase (PAM) converts peptides with COOH-terminal -Gly into the corresponding amide in a 2-step reaction; the peptidyl α-hydroxylating mono-oxygenase (PHM) domain of PAM generates a hydroxy-Gly intermediate that is the substrate for the peptidyl α-hydroxyglycine α-amidating lyase (PAL) domain of the enzyme.