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Copper deficiency alters rat peptidylglycine alpha-amidating monooxygenase activity
J R Prohaska1, W R Bailey, P M Lear
1Department of Biochemistry and Molecular Biology, University of Minnesota, Duluth 55812, USA.
Insights
Perinatal copper deficiency in rats reduced key cuproenzymes like peptidylglycine alpha-amidating monooxygenase (PAM) and cytochrome c oxidase (CCO). These enzyme changes persisted even after copper repletion, suggesting long-term impacts.
Area of Science:
- Biochemistry
- Neuroscience
- Nutritional Science
Background:
- Copper is an essential trace element vital for numerous physiological processes.
- Cuproenzymes, copper-dependent enzymes, play critical roles in cellular metabolism and neurotransmitter synthesis.
- Perinatal copper deficiency can lead to significant health impairments.
Purpose of the Study:
- To investigate the impact of perinatal copper deficiency on cuproenzyme activity in Sprague-Dawley and Holtzman rats.
- To assess the reversibility of these changes following copper repletion.
Main Methods:
- Induction of copper deficiency in pregnant Sprague-Dawley rats from day 7 of gestation.
- Analysis of cuproenzyme activities (PAM, CCO, SOD, DBM) in heart and midbrain tissues of offspring.
- Copper repletion study in deficient rats.
- A separate study in weanling male Holtzman rats subjected to copper deficiency.
Main Results:
- Copper-deficient rats showed characteristic deficiency signs and significantly reduced liver copper levels.
- Activities of peptidylglycine alpha-amidating monooxygenase (PAM), cytochrome c oxidase (CCO), and Cu,Zn-superoxide dismutase (SOD) were lower in copper-deficient rats.
- Dopamine-beta-monooxygenase (DBM) activity showed differential changes, increasing in the midbrain but decreasing in the heart.
- Some enzyme deficits, particularly PAM and CCO, persisted after one month of copper repletion.
- Elevated midbrain DBM activity in males also persisted post-repletion.
Conclusions:
- Perinatal copper deficiency significantly impairs the activity of critical cuproenzymes in rats.
- The observed deficits in PAM and CCO activity suggest potential compromises in neuropeptide maturation.
- Copper deficiency may have lasting effects on enzyme function, impacting neurotransmitter pathways and cellular respiration.
Abstract:
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 alpha-amidating monooxygenase (PAM), cytochrome c oxidase (CCO), and Cu,Zn-superoxide dismutase (SOD) in heart and midbrain samples. Activity of dopamine-beta-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.