FINAL: copper

Question 1

acute ingestion of copper leads to

Answer 1

epigastric pain
anorexia
vomiting
diarrhea

Question 2

food source copper

Answer 2

oysters
crab
liver
legumes
nuts

Question 3

biological form of copper

Answer 3

Cu2+

Question 4

brush border transporters of copper

Answer 4

1. Ctr1: transports Cu1+ (reduced, cuprous)
2. DCT1: transports Cu1+, Cu2+, Fe2+

Question 5

key chaperone for Cu

Answer 5

Atox1

transports Cu from Ctr1 to ATP7A in trans-Golgi network
ATP7A then expels Cu into circulation

Question 6

main IC Cu transporter

Answer 6

ATP7A

Question 7

role of ATP7A, what is it dependent on

Answer 7

role: extrude Cu into portal blood
ATP7A is dependent on ATP

Question 8

__% Cu absorption

Answer 8

12-60% Cu absorption

Question 9

Cu absorption __ with increased intake

Answer 9

Cu absorption decreases with increased intake

Question 10

Cu absorption

Answer 10

1. Cu bound to food broken down to Cu2+
2. reductases (Steap2 + DcytB) turn Cu2+ to Cu1+
3. Cu1+ enters via Ctr1 (DCT1 may also help)
4. Cu1+ bound by chaperone (Atox1) which takes Cu1+ to ATP7A
5. Cu1+ leaves cell –> proteins bind in blood (mainly albumin)

Question 11

storage and distribution of Cu
normal Cu intake =
excess Cu intake =

Answer 11

storage and distribution of Cu
normal Cu intake = ceruloplasmin formed
excess Cu intake = excreted in feces

Question 12

enhancers of Cu absorption

Answer 12

1. some amino acids
2. decreased pH
3. glutathione
4. acids

Question 13

inhbitors of Cu absorption

Answer 13

1. increased pH
2. phytic acid

Question 14

Cu path to bile

Answer 14

1. Cu enters via Ctr1
2. Atox1 takes Cu to TGN to make ceruloplasmin (CP)
3. CP brings Cu to extrahepatic tissue
4. with excess Cu, ATP7B picks up Cu
5. ATP7B brings Cu to bile

Question 15

__% Cu lost in feces

Answer 15

>95% Cu lost in feces

Question 16

__ controls secretion of Cu to bile

Answer 16

ATP7B controls secretion of Cu to bile

Question 17

Cu dependent proteins (5)

Answer 17

1. ceruloplasmin (hephaestin, DcytB)
2. superoxide dismutase (SOD)
3. dopamine monooxigenase (dopamine –> norepinephrine)
4. lysyl oxidase (stablizes connective tissue: collagen)
5. cytochrome c oxidase (mitochondrial electron transport: energy!)

Question 18

superoxide dismutase is essential for __ protection

Answer 18

superoxide dismutase is essential for free radical protection

Question 19

__ or __ SOD in cytosol
__ SOD in mitochondria

Answer 19

Cu or Zn SOD in cytosol
Mn SOD in mitochondria

Question 20

what does SOD NEED to work

Answer 20

Cu, Mn, AND Zn

Question 21

decreased SOD in tissues =

Answer 21

more labile to damage by ROS

Question 22

assessing Cu, best to use

Answer 22

multiple markers

Question 23

4 options for assessing Cu

Answer 23

1. serum, plasma, RBC (common, but variable)
2. plasma CP (good for early manifestation)
3. Cu-dependent enzymes (SOD, sensitive to long-term deficiency)
4. urinary excretion (falls once deficiency is already established

Question 24

is primary Cu deficiency common?

Answer 24

no, it is rare

Question 25

at risk populations for primary Cu deficiency

Answer 25

1. excess Zn consumption (MT) 2. chronic kidney failure 3. patients on dialysis 4. malabsorption (GI resection, Crohn's) 5. genetic alterations that affect abspt and transport (Wilson's disease, Menkes disease)

Question 26

Cu deficiency symptoms

Answer 26

1. hypochromic microcytic anemia (impaired CP mediated oxidation of iron) 2. leukopenia 3. hypopigmentation of hair and skin 4. alterations in connective tissue 5. neurological abnormalities (in fetal and neonatal deprivation)

Question 27

Wilson's disease

Answer 27

1. defect in ATP7B (Cu storage disease) 2. Cu can't get to bile, stays in cell 3. damaged mitochondria: autophagy of mito --> lysosomes

Question 28

Menkes disease

Answer 28

more severe 1. X-linked neurodegenerative disease (ATP7A mutation) 2. low serum copper = accumulation in intestinal cells and other cells 3. death by 3 years of life