Copper

Question 1

What are the two valence states that copper is found in?

Answer 1

Cuprous (Cu1+) or Cupric (Cu2+)

Question 2

The copper content of the human body ranges between ___ to ___mg?

Answer 2

50-150mg

Question 3

Copper is best absorbed in which state?

Answer 3

Cuprous (Cu1+) state

Question 4

Copper is absorbed through the brush border using 3 different transports. What are they?

Answer 4

1. Copper transporter 1 (Ctr1)
2. DMT1 which symports Cu1+ and H+ simultaneously
3. Amino acid transports for cysteine and histidine

Question 5

High intakes of calcium and iron compete with which transporter?

Answer 5

DMT1

Question 6

Much like Iron, Copper ions can damage cells through what reaction?

Answer 6

The non-enzymatic Fenton Reaction

Question 7

Due to the Fenton Reaction issue, what 1 of 3 things is Copper always found to be bound to?

Answer 7

1. Glutathione
2. Metallothionein
3. 1 of 6 chaperone proteins

Question 8

What are the 6 chaperone proteins for Copper?

Answer 8

1. Cox17
2. Cox11
3. Sco1
4. Sco2
5. Atox1
6. CCS

Question 9

There are four chaperone proteins that are specifically for Chytochrome C oxidase synthesis… which proteins are these?

Answer 9

1. Cox17
2. Cox11
3. Sco1
4. Sco2

Question 10

What chaperone protein is used for Cu1+ [Cuprous] transport? (hint: 1 protein)

Answer 10

1. Atox1

Question 11

What chaperone protein is used for SOD (superoxide dismutase) synthesis? (hint: 1 protein)

Answer 11

1. CCS [copper chaperone for superoxide dismutase]

* Note: CCS may be clinically relevant for assessing Cu status*

Question 12

What two things are responsible for transporting Copper in the portal blood to the liver? (hint: 2 proteins)

Answer 12

1. Albumin

2. Transcuprein

Question 13

What Ferroxidase enzyme is responsible for delivering Copper to extrahepatic tissues?

Answer 13

Ceruloplasmin (Ferroxidase 1)

Question 14

How many binding sites does Ceruloplasmin contain for copper?

Answer 14

6

Question 15

When binding to Ceruloplasmin, what form does Copper need to be in? (Hint: Cu1+, Cu2+ etc.)

Answer 15

Either Cu1+ or Cu2+ will bind!

Question 16

What percentage of circulating Copper released into the blood, from the liver, does Ceruloplasmin constitute?

Answer 16

60-70%

Question 17

How is this Copper (Ceruloplasmin) then delivered to extrahepatic tissues?

Answer 17

Ceruloplasmin receptors

Question 18

What is the main storage site for Copper, and what is it bound to?

Answer 18

Liver and it is bound to Metallothionein

Question 19

How many Copper atoms can Metallothionein store?

Answer 19

12 atoms

Question 20

Being able to store this many Copper atoms helps decrease what affect Copper can have on the body?

Answer 20

Reduce oxidative effects of Copper when it produces superoxide and hydroxyl radicals!

Question 21

T/F Copper participates as an enzyme cofactor but not an allosteric component of enzymes…

Answer 21

FALSE. Copper participates as an enzyme cofactor OR an allosteric component of enzymes.

Question 22

Where does Copper function as an intermediate? (hint: pathway?)

Answer 22

ETC [electron transport chain]

Question 23

What are the 9 different metalloenzymes that require Copper that we cover in class?

Answer 23

1. Ceruloplasmin (Ferroxidase 1)
2. Cytochrome C Oxidase (aka Complex IV)
3. Superoxide Dismutase
4. Hephaestin
5. Dopamine Hydroxylase (Dopamine monooxygenase)
6. Monoamine oxidase (Amine oxidase)
7. Tyrosinase
8. Peptidylglycine a-amidating monooxygenase
9. Lysyl Oxidase

Question 24

What is the glycoprotein that transports copper but is also known as an oxidative enzyme and antioxidant?

Answer 24

Ceruloplasmin (Ferroxidase 1)

Question 25

Ceruloplasmin (Ferroxidase 1) is responsible for the oxidation of which two minerals?

Answer 25

Ferrous (Fe2+) Iron and Manganese (Mn2+)

Question 26

Ferroxidase 1 is required to get iron to bind to transferrin for transport to what tissue, and for what type of synthesis?

Answer 26

Transport to Bone Marrow for HEMOGLOBIN synthesis

Question 27

Cytochrome C oxidase (aka complex IV) is specifically in what step of ETC?

Answer 27

Terminal oxidative step

Question 28

Cytochrome C oxidase contains 3 copper atoms per molecule, where are they located?

Answer 28

2 are located in CuA | 1 is located in CuB

Question 29

Where is superoxide dismutase (SOD) found? (hint: think cell location)

Answer 29

1. Cytosol of cells | 2. Extracellularly

Question 30

Besides Copper, what other mineral is linked to this enzyme? (SOD)

Answer 30

Zinc

Question 31

Where is Copper specifically located on the SOD enzyme?

Answer 31

The active site

Question 32

If you were to remove copper, and not zinc what would happen to the activity of SOD?

Answer 32

REDUCED SOD activity

Question 33

What is the purpose of the enzyme Hephaestin, and what does it do with the mineral it transports?

Answer 33

It is essential for oxidizing iron to its Fe3+ state so that dietary iron can be transported from the enterocyte to the portal blood **[Note: Cu deficiency can lead to Anemia in relation to this mechanism]**

Question 34

Dopamine Hydroxylase is also known as what?

Answer 34

Dopamine Monooxygenase

Question 35

How many Copper atoms does Dopamine Hydroxylase require per molecule [of dopamine hydroxylase]?

Answer 35

8 Copper atoms

Question 36

Copper functions as an allosteric structural component of what enzyme? This enzyme can also be inhibited by what type of drugs?

Answer 36

``` Monoamine oxidase (aka Amine oxidase) Inhibited by antidepressant drugs [MAOI's] ```

Question 37

Tyrosinase produces what substance?

Answer 37

Melanin

Question 38

What will a deficiency in Tyrosinase lead to?

Answer 38

Albinism

Question 39

Amidation of peptide hormones resulting in the cleavage of carboxy terminal of glycine which in turn will leave behind a terminal amide is the result of what metalloenzyme? [hint: super long but could be shortened to PG-a-A-M]

Answer 39

Peptidylglycine a-amidating monooxygenase

Question 40

What will generate cross-links between connective tissue proteins such as elastin and collagen?

Answer 40

Allysine

Question 41

What enzyme takes a Lysine residue and forms a collagen chain?

Answer 41

Lysyl oxidase

Question 42

Knowing now how Lysyl oxidase can affect collagen synthesis, a deficiency in what can be integral in different connective tissue defects?

Answer 42

Copper deficiency | *[by way of not acting upon lysyl oxidase]*

Question 43

What else is Allysine required to form, as well as what property of connective tissue is it crucial for?

Answer 43

Desmosine cross-links in ELASTIN | Crucial for STRETCHINESS of this connective tissue

Question 44

What does the liver use to excrete copper? (hint: it's a P-type ATPase)

Answer 44

ATP7B

Question 45

What disease is characterized by defective biliary copper excretion, and is caused by an inherited disorder involving mutations in the gene for ATP7B?

Answer 45

Wilson's disease

Question 46

What is another name for ATP7B?

Answer 46

Wilson's ATPase

Question 47

Wilson's disease is a genetic disorder characterized by copper toxicity. When patients have Wilson's disease, what other mineral is recommended for them to take to decrease their copper absorption?

Answer 47

Zinc supplements (>40mg/day)