Molecular Mechanisms of Human Copper distribution and Homeostasis

Question 1

Which copper-containing enzyme is responsible for cellular respiration?

Answer 1

Cytochrome oxidase.

Question 2

Which copper-containing enzyme is responsible for neurotransmitter biosynthesis?

Answer 2

Dopamine beta-hydroxylase

Question 3

Which copper-containing enzyme is responsible for maturation of peptide hormones?

Answer 3

Peptide aplha-amidating enzyme.

Question 4

Which copper-containing enzyme is responsible for free radical scavenging?

Answer 4

Superoxide dismutase.

Question 5

Which copper-containing enzyme is responsible for crosslinking of elastin?

Answer 5

Lysol oxidase

Question 6

Which copper-containing enzyme is responsible for crosslinking of keratin?

Answer 6

Sulfhydryl oxidase

Question 7

Which copper-containing enzyme is responsible for melanin production?

Answer 7

Tyrosinase

Question 8

Which copper-containing enzyme is responsible for iron homeostasis?

Answer 8

Hephaestion ferroxidases

Question 9

What is ATP7A?

Answer 9

Moves copper back into the blood.

Question 10

What is the function of CCS?

Answer 10

The chaperone of copper.

Question 11

What is the function of ATP7B?

Answer 11

Binds to copper and moves it to the Golgi apparatus

Question 11

What is CTR1?

Answer 11

Copper transporter

Question 12

What is the 3 destinations in the cell for copper?

Answer 12

1. SOD1 in the cytosol
2. The mitochondria to be incorporated into the respiration chain
3. Cuproenzymes for excretion from the golgi

Question 13

What are the 3 copper chaperones?

Answer 13

1. CCS delivery to SOD1
2. Unknown for delivery to mitochondria
3. Atox1 for movement to golgi

Question 14

What happens when copper is released into the phagosome instead of oxygen species?

Answer 14

Kills bacteria

Question 15

What is the issue with copper killing bacteria?

Answer 15

Bacteria have evolved to pump copper away and prevent cellular death.

Question 16

Why does ATP7A relocalises from the Golgi to the phagosome?

Answer 16

To mediate Cu uptake and downstream production of reactive oxygen.

Question 17

What are ZFP?

Answer 17

Zinc Finger Proteins

Question 18

What is the importance of zinc protein fingers?

Answer 18

Zinc stabilizes DNA for transcription.

Question 19

What happens to zinc protein fingers in high copper concentrations?

Answer 19

Zinc is displaced to CFP which means it no longer binds to DNA which turns off gene function in high concentrations.

Question 20

What happens to the levels of CTR1 mRNA when copper concentration increases?

Answer 20

Decrease

Question 21

What is a chelator?

Answer 21

Forming a a compound containing a ligand (typically organic) bonded to a central metal atom at two or more points.

Question 22

What is the function of CTR1?

Answer 22

Reversible trafficking between plasma and membrane and intracellular vesicles.

Question 23

What is the relationship between Atx1 and Ccc2a?

Answer 23

They are homologues.

Question 24

What is a homologue?

Answer 24

Things of similar structure.

Question 25

Why is it important that Atx1 and Ccc2a are homologues?

Answer 25

The copper binding domain is similar but the charge difference and therefore protein-protein interaction ensure copper transfer.

Question 26

How does SOD1 acquire Cu from CCS?

Answer 26

CCS takes oxygen and forms disulphides which drive the movement (displacement) of copper.

Question 27

Briefly describe the cycle of CCS copper movement.

Answer 27

Docked heterodimer contains zinc.

O2 leads to disulphide formation.

Cu attaches to complex

Disulphide isomerization

Cu released and CCS reused.

Question 28

Why can CCS be reused?

Answer 28

Forms a reversible bond with Cu

Question 29

How is copper regulated in response to hypoxia?

Answer 29

Levels of CTR1 increase which means the levels of cu in the macrophage increase.

CCS, SOD1 and Cco decrease in concentration, ATP7A increases so copper moves to the Golgi.

Ceruloplasmin (oxidase) which contains Cu is required for the mobilization of iron out of the Golgi to aid reversal of hypoxia.

Question 30

What occurs when there is low cardiac copper?

Answer 30

This activates ACTP7A to spit more copper towards the heart.

Question 31

What happens when you get a knockout mouse with a CTR1 deletion?

Answer 31

ATP7A expression levels are really high.