Copper Deficiency Alters Rat Peptidylglycine α-Amidating Monooxygenase Activity

Perinatal copper deficiency was studied in 1-mo-old female and male Sprague-Dawley rat offspring to investigate changes in cuproenzymes. Offspring of dams given the low Cu treatment beginning at d 7 of gestation exhibited signs characteristic of Cu deficiency, including a 90% reduction in liver Cu levels compared with Cu-adequate controls. Compared with Cu-adequate rats, Cu-deficient rats had lower activities of the cuproenzymes peptidylglycine α-amidating monooxygenase (PAM), cytochrome c oxidase (CCO), and Cu,Zn-superoxide dismutase (SOD) in heart and midbrain samples. Activity of dopamine-β-monooxygenase (DBM) was higher in midbrain and lower in heart samples from Cu-deficient compared with Cu-adequate rats. Following 1 mo of Cu repletion, PAM and CCO activity were still lower in heart of Cu-replete rats. Midbrain DBM activity was still elevated in the former Cu-deficient males. A second study was conducted using weanling male Holtzman rats. After 5.5 wk of treatment, Cu-deficient rats had signs characteristic of Cu deficiency and lower PAM, CCO and DBM activities in heart but not midbrain as compared with Cu-adequate rats. The PAM activity was lower following Cu deficiency. Perhaps neuropeptide maturation is compromised by Cu deficiency.