Basic Metal Biochemistry Flashcards
Why are metals important for human function?
Nearly 50% of proteins require a metal for function.
How do metals exist within the body?
As a salt or bound up in protein but always containing a charge.
Which metallic form in the body releases the most energy?
The compound form
What is the amount of energy release by a metal directly proportional to?
The stability of the compound.
What happens when a protein forms around a metal?
Forms an exothermic stable lattice structure.
What does it mean if a metal-containing protein is very exothermic?
Very stable,
What things do we need to consider when testing the stability of a metal-containing compound?
Amount of energy to ionise the metal
Amount of energy released when the compound forms, as lattice energy (solids) or hydration enthalpy (solutions)
What kind of metallic reactions mostly do not occur in the body?
Large endothermic
What is metal centre geometry?
Arrangement of the protein primary and secondary coordination sphere around the metal.
What is important about the metal centre geometry?
Tune the properties of the metal to aid reactivity and selection.
How does haem attach to the RBC?
Attached to the unoccupied ligand.
Which residue binds to iron?
Cysteine
What are the functions of metals in the body?
Structural
Catalytic
How are metals used structually?
Can aid the correct folding of structures.
What deficiencies lead to Alzheimer’s?
Zn and Cu
What does zinc anaemia lead to?
Growth rertardation
What metal cluster does aconitase contain?
Iron
Which metal stabilizes DNA?
Zinc
What is the function of aconitase?
Responsible for the stereospecific isomerisation of citrate to isocitrate.
What is the function of superoxide dismutase (SOD)?
The disproportion of superoxides, this protects the cell from harm.
How does aconitase work?
Leave one iron solvent-exposed to bind to the reactant.
Which metals does SOD contain?
Copper and zinc
What is the function of zinc in SOD?
Structural element
Where are metals limited?
Oceans
What is the function of copper in SOD?
Catalytically active metal
Why does metal content differ between species?
Environment availablity
What is the reduction stratergy?
Reducing Fe3+ back down to 2+
What is chelation?
PS binds to Fe3+ allowing it to move back into the cell where it will be reduced.
What are the evolutionary mechanisms for acquiring iron?
Reduction strategy
Chelation
What evolutionary tactic is the last resort?
Changing the metal used or the amount required.
What is the Irving-Williams Series?
The order of metal strength.
Which is the weakest metal in the body?
Mg(II)
What does it mean if a metal is weak?
Bound so can release copart easily.
Which metal is the strongest?
Zn(II)
What does it mean when a metal is strong?
More structural non-catalytic binding structure.
What is the ligand -strong theory?
How closely bound the ligand is to the metal.
How is metal binding controlled in the body?
Cells must have a mechanism to make sure the correct metal gets to the protein.
What happens when spores enter an immunocompromised patient?
Spores can cross the blood-brain barrier due to urease activity.
Cobalt forces out urease.
Why can metals lower (eg. Colbalt) displace metals higher on the Irving-Williams Series?
Larger concentrations can outcompete metals higher in the series.
What is the effect of metals on oxidative stress?
Metals drive the transformation of hydrogen peroxide during the Fenton reaction causing oxidative stress.
What are radicals?
Radicals can react with anything and cause damage.
What are antioxidants?
We take them to remove radicals.
How does the replacement of metals lead to the loss of activity or function?
Higher-function metals can have the same structural function but no catalytic function.
What is the protoporphyrin example of metal replacement function loss?
Iron can be subbed with zinc, it is structural so there is no more catalytic function , this leads to anemia.
Why is zinc protoporphyrin important?
Can be quantified to test for anaemia.
How are metals transported into the cell?
By recycling or dietary uptake.
What are the mechanisms needed for each biological metal?
Sensing how much is in the cell and how much is needed.
Distribute metal to the correct location.
Store, export or prevent uptake of excess metals.
What distributes metals to the correct location?
Chaperones
Why do we need to keep metals at homeostasis?
Ensure metal need is met and nay free cellular metal does not cause oxidative stress or inhibit protein function.
Which transporters move Mg?
MgtA
CorA
Which transporter moves manganese?
MntH (NRAMP)
Which transporters move Iron?
FhuA-E
FepA-E
FecA-E
EfeU/O/B
FeoA/B
Which transporters move nickle?
NikA-E
RcnA
Which transporter moves colbalt?
RcnA
Which transporters move zinc?
ZupT
ZnuA
ZntA
Yiip
ZitB
What transporters move copper?
CopA
CusA-C
What acts as sensors in metal homeostasis?
Transcription factors
How does metal sensing work?
Metal binding causes an allosteric change,
How does binding sensitivity change depending on the metal?
Increases moving up the Irving Williams series meaning the transcription factors are more sensitive.
Which Transcription factors regulate iron concentration in the cells?
Aft1/2
How do aft1/2 control the concentration of iron?
Fe-S signal relay caused by aft1/2 moves iron out of the nucleus.
When there is no Fe cluster, there is no signal relay and therefore concentration is maintained.
What maintains the concentration of copper?
Apo Mac1
How does Apo Mac1 control the concentration of Copper?
Apo Mac1 seeks out copper, the binding inactivates Mac1.
Why does yeast need copper to survive?
To survive DNA damage.
What is CTR1?
A copper transporter.
How does copper prevent DNA damage in yeast?
MethylMethaneSulfonate (MMS) methylates N7-guanine residue.
When copper is complimented it binds to the damaging agent preventing the damage.
What is MethylMethaneSulfonate (MMS)?
A DNA damaging agent.
What is MTF1?
Human metal-responsive transcription factor
What is Metallothionine (MT)?
Protectant against Cadmium.
How does MT protect against Cadmium toxicity?
Cadmium displaces Zinc on MT, the zinc then binds to MTF1 activating the transcription of Metallothionine which removes more Cd.
What is transporter degardation?
Turning off the import of metals.
When are ZIP transporters present?
High concentrationsW
When are transported degraded?
When the concentration drops the ZIP transporters are endocytosed and cleaved.
When the concentration is low the ZIP transporter is degraded.
What is hepcidin?
Regulates Ferroportin (FPN) release and regulates iron in the cell.
What is ferroportin?
An iron exporter.
What are metal chaperones?
Involved in the delivery of the right metal to the protein.
How to chaperones work?
Binding to the metal prevents it from binding else where until it is in the right place.
How does compartmentalisation help metal homeostasis?
Keeps metals in their place and prevents travel to unnecessary places.
