Peptidylglycine-α-amidating monooxygenase activity and protein are lower in copper-deficient rats and suckling copper-deficient mice

Peptidylglycine-α-amidating monooxygenase (PAM) is a copper-dependent enzyme involved in peptide posttranslational activation. Dietary Cu deficiency (Cu−) was studied to determine if lower PAM activity was due to reduction in protein or cofactor limitation. PAM activity was lower in cardiac atria of Cu− rats than Cu-adequate (Cu+) rats and there was a 50% equivalent reduction in PAM protein. No reduction in Cu− rat midbrain PAM protein was detected although PAM activity was reduced 40%. In 12-day-old (P12) mouse pups derived from dams that began Cu deficiency on day 7 of gestation, there was a parallel reduction in brain PAM activity and protein of 40-50%. PAM mRNA levels assessed in atria and brains from Cu+ and Cu− rats and mice were not altered by dietary treatment, suggesting a posttranscriptional mechanism for lower PAM protein when Cu is limiting in the cell, perhaps due to enhanced apoprotein turnover.