Copper Flashcards
Copper and iron reduced and oxidized forms
Cu+1, Fe+2 = reduced
Cu+2, Fe+3 = oxidized
Cu absorption rate
50-80%
enhancers of Cu absorption
some aa
low pH
glutathione
acids
inhibitors of cu absorption
high pH
phytic acid
zinc
7 steps of Cu absorption
- Cu+2 released from food
- reduce to Cu+1 by reductase
- Cu+1 cross BBM by high-affinity Ctr1 transporter and DMT1
- in cytosol, copper binds to ‘chaperone’ for transport to target enzymes. Atox1 transports Cu+1 to trans-golgi network (TGN) which ATP7A relocates to BLM where it functions to export Cu from enterocyte
- copper delivered to enzymes by chaperones to use in some cells or bind to METALLOTHIONEIN for storage
- ATP7A transports Cu+1 across BLM
- copper attaches proteins for transport in blood. after hepatic uptake of copper, most copper is found in blood as ceruloplasmin
Cu transport
Ceruloplasmin leaves liver with Cu and delivers 60-70% of the Cu to tissues
**Unlike Fe and Zn, Cu excretion is regulated to maintain Cu homeostasis (balance)
Major route: excess Cu secreted into bile (exocytosis of vesicles containing Cu)
iron oxidation
ceruloplasmin:
Cu+2 converts Fe+2->Fe+3 for import/use in cells = ceruloplasmin-Cu+1 at end
(also functions to transport Cu in plasma to deliver to tissues)
hephaestin:
Cu+2 does this at enterocyte-Fe transport
low Cu cause microcytic anemia bc can’t utilize iron stores or from enterocyte
CuZn Superoxide Dismutase (CuZnSOD)
In cell cytosol, requires both Cu and Zn
CuZnSOD activity sensitive to amount of copper [Cu2+ at active site] -> CuZnSOD role in anti-oxidant defense
Lysyl oxidase:
Converts NH2 of lysine or OH-lysine to an aldehyde to allow cross-linking
of collagen
Cytochrome c oxidase
energy production
contains Cu atoms to receive/transfer electrons
Role of Cu Chaperones
complex series of intracellular proteins bind the Cu and deliver it to the specific enzymes where it is needed.
for adding copper to cytochrome oxidase subunits COX1
and COX2
RDA Cu
= 900mcg
EAR based on Cu
maintaining normal plasma Cu and RBC superoxide dismutase (ZnCuSOD)
Food Sources
nuts& oysters, organ meats, shellfish, seeds, cocoa, NOT F&V
cooking with copper pots
water in copper pipes
less in refined flour/ grains
dietary copper not assessed
Cu deficiency causes
excess Zn supplementation
malabsorptive disorders
Cu deficiency symptoms
microcytic, hypochromic anemia (can’t release Fe from cells)
neutropenia (low neutrophils WBC)
impaired immunity
hypopigmentation – hair and skin
blood vessel/connective tissue and bone abnormalities- collagen crosslinks
hypotonia- decrease muscle tone
altered cholesterol metabolism-role in lipid metab
cardiovascular dysfunction- important to maintain CV health
Cu UL
10mg
toxicity: Cu accumulates in organs especially in liver
reasons for Cu toxicity
- if a patient has problems in secreting bile from the liver, caution about adding Cu to an intravenous feeding to avoid Cu build up
- Wilson’s Disease: genetic disease of abnormal Cu accumulation
- liver disease w psychiatric or neurological symptoms
- tremors, difficulty coordinating movement and speech
Wilson’s disease treatments
zinc supplements- reduce absorption of Cu
reduce dietary cu (avoid nuts, shellfish, chocolate)
chelation drugs to bind Cu and prevent build up
