Copper

Question 1

Is copper supplementation necessary?

Answer 1

No. Trace minerals generally do not need supplementation.

Question 2

Cuprous and Cupric Copper

Answer 2

+1 reduced (absorbable)
+2 oxidized

Use chaperones so they’re not unnecessarily used within the body.

Question 3

What can reduce copper or keep it reduced?

Answer 3

Amino acids
Organic acids
Vitamin C
Cytochrome B

Question 4

Passive diffusion

Answer 4

Only occurs when copper is in excess.

Question 5

DMT (divalent metal transporter)

Answer 5

Active transporter.

Regulated by iron status. Can transport iron as well.

50% absorbed via DMT

Question 6

Ctr1 (copper transporter 1)

Answer 6

Regulated based on copper status.

50-80% absorption

Question 7

Amino acid carriers

Answer 7

Minor copper transporter.

Question 8

Which vitamins compete with copper absorption?

Answer 8

Zinc
Iron
Calcium
Phytates

Antacids reduce absorption because it lowers pH.

Question 9

Metallothionine

Answer 9

Zinc regulates metallothionine.
Copper binds better than zinc.

If excess zinc, Cu can’t leave enterocyte because it’s bound to metallothionine

Stored for 2-3 days.

Question 10

ATP7A

Answer 10

Protein that helps copper leave enterocyte.

Active transport.

Question 11

Portal blood

Systemic blood

Answer 11

Binds to albumin

Binds to ceruloplasmin. Oxidizes iron. Antioxidant.

90% of copper is bound to ceruloplasmin.

Question 12

Anemia

Answer 12

Copper deficiency can lead to anemia because most copper is bound to ceruloplasmin which oxidizes iron.
Iron binds to transferrin to be transported to bone marrow to make hemoglobin.

Question 13

Chaperones

Answer 13

Copper is chaperoned on proteins to prevent oxidation reactions.

Glutathione, Atox1, Cox17

Question 14

Liver has complete control of copper.
Storage
Transport
Excretion

Answer 14

Storage: Copper stored in metallothionine.

Transport: Ceruloplasmin is produced in liver, binds to copper, released into systemic blood.

Excretion: ATP7B puts copper in bile to be excreted.

Question 15

Menke’s Disease

Answer 15

Genetic defect not polymorphism.

Cannot make protein ATP7A. Cannot absorb copper.

Children die in infancy.

Copper treatment does not expand lifespan.

Question 16

Wilson’s Disease

Answer 16

Cannot excrete copper.
Copper toxicity in muscles and liver. Iris.

Chelation. Zinc. Low copper diet.

Question 17

Sources

RDA: .9 mg

Answer 17

Best: liver, organ meats

Typical: nuts, cashews, potato, whole grains

Bioavailability 50-80%
Increases when Cu status is low

Question 18

Biochemical Assessment

Answer 18

Serum copper (static)

Serum ceruloplasmin activity (functional)

Question 19

Functions

Answer 19

Coenzyme. Enzymes that need a reduced metal.

Ceruloplasmin: antioxidant, oxidizes iron (ferroxidase)

Cytochrome c Oxidase: used in ETC to transport e-

Question 20

Deficiency

Answer 20

At risk if using antacids and zinc supplements (40mg/d).

Hypochromic anemia: most Cu is bound to ceruloplasmin which transfers Fe to transferrin to bone marrow to make blood
Leukopenia: impaired immune function
Hypopigmentation: depigmentation of hair

Zinc toxicity makes copper deficiency because metallothionine is upregulated and Cu binds to it.

Iron toxicity makes Cu deficiency because DMT1 is down regulated which absorbs 50% of Cu

Question 21

Toxicity

Answer 21

10 mg/day

Nausea, vomiting, diarrhea, kidney and liver damage.

Question 22

Kayser-Fleischer Ring

Wilson’s Disease

Answer 22

Copper toxicity. Ring around the eye.

Question 23

Cytochrome c Oxidase

Answer 23

Last step in ETC.

Contain 3 Cu atoms on 2 subunits:
The first subunit contains 2 Cu atoms that receive e from cytochrome c.

Transfer to second subunit to reduce oxygen.

Creates ATP.

Question 24

Nutrient interactions

Answer 24

Iron: low Cu that leads to low ceruloplasmin which traps iron in the cells. Secondary iron deficiency anemia.

Molybdenum: enhances copper excretion.

Question 25

ATP7B

Answer 25

Within the hepatocyte, transfers Cu to bile to be excreted.

Question 26

Ceruloplasmin

Answer 26

Synthesized in liver.

90% of copper bound in systemic blood

Functional measure of copper status.

Oxidizes iron so it can get on to transferrin to make blood.

Antioxidant.