Chemistry of Zn

Question 1

why are metals important to proteins?

Answer 1

as nearly 50% of proteins require a metal to function

Question 2

What important reactions/processes do metals take part in?

Answer 2

1. catalysis
2. transport
3. signalling

Question 3

what processes are metal ions vital for?

Answer 3

1. transcription
2. translation
3. signalling
4. transport

Question 4

Redox inert metals aren’t involved in redox processes, instead they’re used for what?

Answer 4

for structural roles and Lewis acid catalysts in enzymes

Question 5

why can’t redox inert metals facilitate redox processes but redox active metals can?

Answer 5

because redox inert metals have only one oxidation state but redox active metals have two or more oxidation states so can carry out redox reactions

Question 6

what role does zinc have in enzymes?

Answer 6

it’s a catalytic and structural cofactor in enzymes

Question 7

how is cellular zinc homeostasis controlled?

Answer 7

controlled by proteins which store and release zinc. They bind to any excess zinc to avoid unspecific reactions. They transport zinc through membranes and cellular compartments.

Question 8

what is the function of ZnTs (zinc transporters)?

Answer 8

to decrease the cytosolic zinc concentration by transporting zinc from the cytosol to the extracellular space or into intracellular compartments

Question 9

What is the role of the bacterial ZnT homolog YiiP?

Answer 9

it is a membrane transporter catalysing the exchange of Zn2+/H+ across inner membrane of E.coli

Question 10

What are ZIP responsible for?

Answer 10

zinc uptake in the body

Question 11

what is the role of ZIP4 and where is it most commonly expressed?

Answer 11

• most commonly expressed in GI tract on apical surface of enterocytes
• major zinc transporter responsible for dietary zinc uptake

Question 12

what happens if there’s a mutation of ZIP4?

Answer 12

causes the inherited zinc deficiency disease, acrodermatitis enteropathica (AE)

Question 13

what is the function of the Cys2His2 (C2H2) zinc finger group (ZnF)?

Answer 13

• binds RNA

- mediates protein-protein interactions

Question 14

In HIV, nucleocapsid protein 7 (NCp7) is targeted by zinc ejectors, why?

Answer 14

• because NCp7 causes the unwinding of tRNA and acts as the primer for reverse transcriptase.
• by targeting this protein, they eject the zinc from it hence destabilising the protein’s structure making it less likely to work like it should. (so preventing viral cell replication)

Question 15

three examples of zinc fingers inhibitors (aka HIV treatments)?

Answer 15

1. Azodicarbonamide
2. C nitroso
3. 2,2-dithiobisbenzamide

Question 16

what is the mechanism of action of the zinc fingers inhibitors?

Answer 16

• attacks sulphur atoms of Zn coordinated cysteine

- hence distorts structure and reduces strength of (breaks) bond b/w Zn and cysteine.

Question 17

what is the role of zinc proteases?

Answer 17

an enzyme that hydrolyses peptide bonds

Question 18

what are the 4 classes of proteolytic enzymes?

Answer 18

1. serine proteases
2. cysteine proteases
3. aspartic proteases
4. metalloproteases

Question 19

all proteases stabilise the formation of a tetrahedral intermediate during catalysis by which two mechanisms?

Answer 19

1. by protease forming a covalent intermediate

2. activated water used to accomplish catalysis

Question 20

what is the role of matrix metalloproteinases (MMPs)?

Answer 20

• degradation of extracellular matrix components (e.g. collagen, laminin and proteoglycans.)
• Involved in embryogenesis and tissue remodelling
• important role in arthritis, periodontitis, wound healing and metastasis.

Question 21

what is the role of ACE?

Answer 21

• catalyses conversion of angiotensin I into angiotensin II

- results I vasoconstriction