signalling metals

Question 1

what is the main zinc transporter?

Answer 1

ZnT-1

Question 2

what is YiiP?

Answer 2

ZIP protein involved in Zn transport
catalyses Zn/H exchange

Question 3

what are ZIPs?

Answer 3

proteins responsible for cellular Zn uptake

Question 4

which ZIP is found in GI tract and uptakes dietary zinc?

Answer 4

ZIP4
mutations lead to zinc deficiency enzyme (AE)

Question 5

what are zinc fingers?

Answer 5

binding domains - bind to DNA sequences
stabilise structure of DNA

Question 6

what is C2H2 zinc finger?

Answer 6

best class - Cys2His2-like fold
binds RNA
mediates protein-protein interactions

Question 7

what is HIV-1 nucleic capsid protein 7 (NCp7)?

Answer 7

inhibits zinc fingers
primer for reverse transcription
facilitates tRNA unwinding
crucial role in HIV-1 replication

Question 8

HIV treatment?

Answer 8

azodicarbonamide
- zinc ejector
attacks sulphur atom of zinc coordinated cysteine

Question 9

what are zinc proteases?

Answer 9

enzymes with metal ion that hydrolyse peptide bond
endopeptidase - cut at defined position internally
exopeptidase - cleave 1st amino acid residue

Question 10

how do zinc proteases stabilise formation of tetrahedral intermediate?

Answer 10

1) form covalent intermediate
2) use activated water to catalyse

Question 11

what are MMPs?

Answer 11

matrix metalloproteinases
- degrade extracellular matrix componenets

Question 12

what allows Fe to be either Fe2+ or 3+?

Answer 12

less increase in ionisation than Ca

Question 13

what are redox inert metals?

Answer 13

cannot facilitate redox reactions - only one oxidation state available

Question 14

what are redox active metals?

Answer 14

can access 2+ oxidation states, can carry out redox reactions

Question 15

what affects properties of the metal to aid reactivity and selection?

Answer 15

primary and secondary coordination spheres of proteins

Question 16

how can cysteine bind?

Answer 16

in bridging fashion (Fe-S) clusters

Question 17

what is haemochromatosis?

Answer 17

disorder of Fe absorption and storage

Question 18

how is Fe stored when taken in by Ferritin (beans and pulses)?

Answer 18

stored as Fe3+ (insoluble) following oxidation

Question 19

how is Fe metabolised?

Answer 19

not excreted, excess stored in liver
uptake regulated by enterocytes

Question 20

how is Fe uptake done?

Answer 20

• redox processes
• oxidase (Cu) and reductase (FAD/NADPH)
• haem iron transporter - ferroportin

Question 21

what does myoglobin do?

Answer 21

promotes O2 diffusion in and through muscle cells

Question 22

what are the 2 conformational states of haemoglobin and myoglobin?

Answer 22

R state (relaxed)
T state (tense)
absence of O2 = T state more stable

Question 23

what is calcium responsible for?

Answer 23

regulating events of cell division
2nd messenger = intracellular signalling
facilitates structural changes

Question 24

what is the role of magnesium?

Answer 24

co-factor - required by enzymes for catalytic action
inadequate intake = muscle spasms

Question 25

what is the role of manganese?

Answer 25

• co-factor
• detoxification of superoxide free radicals
• neurotoxin in large amounts

Question 26

what is the role of arginase?

Answer 26

catalyses 5th and final step in urea cycle

Question 27

what is superoxide dismutase?

Answer 27

SOD - alternately catalyses dismutation of superoxide into O2 or hydrogen peroxide

Question 28

what is superoxide?

Answer 28

by-product of O2 metabolism
if not regulated can cause cell damage

Question 29

what are radionuclides?

Answer 29

metal ions for medicine
- diagnostic imaging
- targeted therapy

Question 30

what are cyclotrons used for?

Answer 30

particle accelerator producing proton beams to manufacture radioisotopes
E.g PET and SPECT