signalling metals Flashcards
what is the main zinc transporter?
ZnT-1
what is YiiP?
ZIP protein involved in Zn transport
catalyses Zn/H exchange
what are ZIPs?
proteins responsible for cellular Zn uptake
which ZIP is found in GI tract and uptakes dietary zinc?
ZIP4
mutations lead to zinc deficiency enzyme (AE)
what are zinc fingers?
binding domains - bind to DNA sequences
stabilise structure of DNA
what is C2H2 zinc finger?
best class - Cys2His2-like fold
binds RNA
mediates protein-protein interactions
what is HIV-1 nucleic capsid protein 7 (NCp7)?
inhibits zinc fingers
primer for reverse transcription
facilitates tRNA unwinding
crucial role in HIV-1 replication
HIV treatment?
azodicarbonamide
- zinc ejector
attacks sulphur atom of zinc coordinated cysteine
what are zinc proteases?
enzymes with metal ion that hydrolyse peptide bond
endopeptidase - cut at defined position internally
exopeptidase - cleave 1st amino acid residue
how do zinc proteases stabilise formation of tetrahedral intermediate?
1) form covalent intermediate
2) use activated water to catalyse
what are MMPs?
matrix metalloproteinases
- degrade extracellular matrix componenets
what allows Fe to be either Fe2+ or 3+?
less increase in ionisation than Ca
what are redox inert metals?
cannot facilitate redox reactions - only one oxidation state available
what are redox active metals?
can access 2+ oxidation states, can carry out redox reactions
what affects properties of the metal to aid reactivity and selection?
primary and secondary coordination spheres of proteins
how can cysteine bind?
in bridging fashion (Fe-S) clusters
what is haemochromatosis?
disorder of Fe absorption and storage
how is Fe stored when taken in by Ferritin (beans and pulses)?
stored as Fe3+ (insoluble) following oxidation
how is Fe metabolised?
not excreted, excess stored in liver
uptake regulated by enterocytes
how is Fe uptake done?
- redox processes
- oxidase (Cu) and reductase (FAD/NADPH)
- haem iron transporter - ferroportin
what does myoglobin do?
promotes O2 diffusion in and through muscle cells
what are the 2 conformational states of haemoglobin and myoglobin?
R state (relaxed)
T state (tense)
absence of O2 = T state more stable
what is calcium responsible for?
regulating events of cell division
2nd messenger = intracellular signalling
facilitates structural changes
what is the role of magnesium?
co-factor - required by enzymes for catalytic action
inadequate intake = muscle spasms
what is the role of manganese?
- co-factor
- detoxification of superoxide free radicals
- neurotoxin in large amounts
what is the role of arginase?
catalyses 5th and final step in urea cycle
what is superoxide dismutase?
SOD - alternately catalyses dismutation of superoxide into O2 or hydrogen peroxide
what is superoxide?
by-product of O2 metabolism
if not regulated can cause cell damage
what are radionuclides?
metal ions for medicine
- diagnostic imaging
- targeted therapy
what are cyclotrons used for?
particle accelerator producing proton beams to manufacture radioisotopes
E.g PET and SPECT
