Zn, Cu, Mn

Question 1

This group is usually defined as transition elements, though which one is not?

Answer 1

Zinc, but has the same properties

Question 2

The equation to get a metalo-complex

Answer 2

Lewis acid (metal ion) + Lewis base (Ligand - AA/H20) –> MLC

Question 3

Four general biological roles of metalloenzymes

Answer 3

signaling
structural
catalytic
regulatory

Question 4

Properties of Zn

Answer 4

Most common ions within the cell (except K+, Mg2+)
Found in every compartment and organelle
Very strong Lewis Acid
One valence state = limited in fxn (2+)

Question 5

What is Zn main role in cytosolic and extracellular SOD

Answer 5

Structural role / folding of the proteins

Question 6

How many AA are required for the zinc finer region or motif

Answer 6

4 AA residues

Question 7

What role do zinc fingers play in gene transcription

Answer 7

folding pattern of a sequence of AA around a loop to stabilize DNA sequence

Question 8

It has been proposed Zn deficiencies can lead to stunted growth in children, why?

Answer 8

IGF-1 receptor is activated by a promoter region that contains a zinc finger DNA binding region

Question 9

Why would Zinc and Copper impair immunity

Answer 9

Zinc (lymphocytes) - maintenance of B & T cells, deficiency can cause decreased thymulin hormones and smaller size thymus (Tcells)

Cu (leukocytes) - regulate neutrophils and granulocytes, maturation of early stem cells, regulates T cell proliferations through IL-2

Question 10

We need ___ for the mobilization of iron

Answer 10

Copper

Question 11

What is the importance of Ceruloplasmin?

Answer 11

Secreted by the liver in response to Cu conc
Involved in transport of 90% of copper around the body
Responsible for oxidation of Fe2 to Fe3+

Question 12

What role does copper play in bone mineralization?

Answer 12

Providing the collagen matrix through lysyl oxidase - linkage enzyme provided to collagen and elastin

Question 13

Cardiac dysfunction due to copper would be from?

Answer 13

deficiency of lysyl oxidase to elastin

Question 14

What is the first step in SOD to remove superoxide

Answer 14

1st step is to change superoxide to hydrogen peroxide

Question 15

Where are the different forms of SOD found?

Answer 15

Cu/Zn: intracellular and extracellular fluids
Mn-SOD: Mitochondria

Question 16

When would reduce SOD activity occur?

Answer 16

deficiency (Zn,Mn,Cu), causing:
- increased lipid peroxidation
- oxidative stress
- reduced energy regulation in mito

Question 17

What part does Mn play in cartilage formation

Answer 17

Syn of glycosaminoglycan - elongation of sulphate chains

Question 18

Where are all 3 element absorbed and how effective is absorption?

Answer 18

Small I
Relatively low - linear related to amount in diet

Question 19

Define intestinal absorption kinetics in terms in saturable and diffusional

Answer 19

Diffusional: defined by linear relationship b/w mineral content and amount absorbed

Saturable: varies dependent upon the mineral content of the intestine (@ low mineral content it is effect, and at high it’s low)

Question 20

In what 2 ways is zinc transported into the intestinal epithelium?

Answer 20

Transcellular transport (ZIP4) + ZnT5B - Brush boarder

Question 21

Inside the cell Zinc and Cu both bind ___? what is the downside to this?

Answer 21

Metallothionein
If one element is too high within the diet, Metallothionein will bind both and cause an unwanted down regulation

Question 22

Metallothionein: properties and role

Answer 22

Low molecular weight protein
Produced to response to high levels of Zn, Cu, Cadmium and mercury
Role: Bind and maybe store metals within the cell
- Block or reduce uptake

Question 23

Enterocytes can accumulate MT-bound metals. How are they removed?

Answer 23

Sloughed off from the mucosa and excreted usually in feces

Question 24

When in ZIP4 upregulated?

Answer 24

During low Zn status

Question 25

Zn and Cu can be reduced by binding of

Answer 25

Calcium and phytates
MT

Question 26

How are Zn and Cu packed to the liver and re-packaged after?

Answer 26

Both bind albumin to the liver
Zn = bound to alpha-2-macroglobulin
Cu= bound to ceruloplasmin

Question 27

What is the plasma distribution of bound-Zin

Answer 27

55-60% albumin
40%- A2-macroglobulin
some residual metalloenzymes

Question 28

How is Cu regulated for export

Answer 28

Cu-ATPase-like proteins

Question 29

Wilson’s disease

Answer 29

ATP7B mutation = copper accumulation in liver + brain
— liver disease and neuropsychiatric symptoms

Question 30

Menkes syndrome

Answer 30

ATP7A mutation - recessive disorder, copper transport deficiency
— beings at infancy, don’t live past 3

Question 31

How is Mn transported to the liver and exported from?

Answer 31

Transport: binds A2-macroglobulin
Exported: thought of as Fe –> transferrin, ferritin, fe mediated absorption

Question 32

How are these minerals excreted

Answer 32

Sloughed off from GI into bile - Zn, Cu
transported into bile from liver - Mn
majority into bile - Cu
—– All end up in feces

Question 33

Zn,Cu,Mn RDA

Answer 33

Zn: 15 (M) -12(F) mg/d (inc with pregnancy
Cu: 1.5-3 mg/d (M and F the same, inc with preg)
Mn: 2.0-5 mg/day (females lower than males, Inc with preg)

Question 34

Are they any assessment for Zn, Cu, Mn ?

Answer 34

None reliable
Zn - does not vary
Cu - ceruplasmin but sensitive to inflammation