Peptidylgycine α‐amidating monooxygenase and copper: A gene–nutrient interaction critical to nervous system function

Peptidylgycine alpha-amidating monooxygenase (PAM), a highly conserved copper-dependent enzyme, is essential for the synthesis of all amidated neuropeptides. Biophysical studies revealed that the binding of copper to PAM affects its structure, and cell biological studies demonstrated that the endocytic trafficking of PAM was sensitive to copper. We review data indicating that genetic reduction of PAM expression and mild copper deficiency in mice cause similar alterations in several physiological functions known to be regulated by neuropeptides: thermal regulation, seizure sensitivity, and anxiety-like behavior.