Chemistry of Fe Flashcards
what is the ground state electron configuration of Fe?
1s2 2s2 2p6 3s2 3p6 3d6 4s2
what is the electron configuration of Fe2+?
1s2 2s2 2p6 3s2 3p6 3d6 (the 4s2 electrons are knocked off instead of the 3d electrons)
what is the electron configuration of Fe3+?
1s2 2s2 2p6 3s2 3p6 3d5 (knocks off 2 from 4s2 and 1 from 3d6)
what are the three common structural complex ions formations?
- octahedral
- tetrahedral
- square planar
which are more stable, higher or lower oxidation states?
lower oxidation states
what are the two categories which ingested iron can be classified into?
- Iron-bearing haem moiety (contains porphyrin ligand system)
- Non-haem containing (no porphyrin ligands)
how is iron used by the body?
- in bone barrow to create reticulo-endothelial macrophages which store the iron
- in muscles (in their myoglobin)
Where is iron mainly stored in the body?
liver parenchyma and reticulo-endothelial macrophages
what 4 main body homeostasis are controlled by Fe?
- metabolism
- oxygen transport
- energy generation
- oxygen transfer
what is the structure of a metallo-protein?
- metal complex in crevice of the protein
- some ligands attached to metal are from the protein (if not all the ligands)
what decides the geometry of the metal bond angles and distances?
the protein unit it attaches to
what is a co-factor?
A non-protein chemical compound bound to a protein and is required for the protein’s biological activity
what are the 4 categories for cofactors?
- organic
- inorganic
- coenzymes
- prosthetic groups
what is the difference between coenzymes and prosthetic groups?
- coenzymes are loosely bound to an enzyme,
- whilst prosthetic groups are tightly bound.
what are protoporphyrin IX?
organic compounds not soluble in basic water. only exists with its iron complex in nature, can’t be found on it’s own.
What are haem’s?
prosthetic groups in haemoglobin, myoglobin and cytochrome C
what is haemogobin?
- red tetrameric protein (red blood cells) comprising of 2 alpha and 2 beta subunits each containing an iron atom bound to a haem group
- promotes the diffusion of oxygen throughout the body
what is myoglobin?
- red protein containing haem
- binds to iron to carry (facilitate O2 diffusion) and store oxygen in muscle cells.
what is myoglobin made up of?
- a single polypeptide chain of 153 amino acids
- and a single prosthetic group
What is the charge of the iron that binds to the haem group on haemoglobin?
Fe2+ (iron in its ferrous state)
How many coordination positions does Fe2+ have, and what do they bind to?
- 6 coordination positions
- 4 in plane on protoporphyrin and bound to it
- 2 perpendicular to this ring with 1 bound to a N atom of a His residue in polypeptide chain and the other free to bind to oxygen.
Why must the Myoglobin haem group be kept away from solvents?
Because Fe2+ can easily oxidise to Fe3+ and this doesn’t bind to oxygen
During oxygenation of myoglobin, what role does distal Histidine have?
Makes oxygen bind to iron in a bent manner and prevent CO binding in a linear manner
what is the amount of oxygen bound a hyperbolic function of?
the amount of oxygen present and the affinity of myoglobin for oxygen
Haemoglobin transitions between 2 conformational states depending on whether O2 is present or not. What are these states?
R state (relaxed) and T state (tensed)
What state is favoured by O2 binding?
the R state. T state is more stable in the absence of oxygen
what happens when O2 binds to Hb in the T state?
triggers a change in the conformation to the R state
When going from T to R state, bonds are broken and new ones are formed. Which bond is one of the most important ones broken during this transition?
the His C3 and Lys C5 bonds
what is the effect of oxygen on the porphyrin ring and the haemoglobin helix?
promotes flattening of the porphyrin ring
and causes a shift in the helix
why is it that once one oxygen molecule binds to one haem group, the other haem groups can bind to oxygen easier?
because that polypeptide changes from T to R state therefore pockets of haem are easier to access due to weak interactions being broken
why can’t myoglobin be used as an oxygen transporter round the body?
because it has a high affinity for oxygen, so will bind to it at the lungs but at the respiring tissues it won’t dissociate. Therefore no more oxygen can bind
what is cooperative binding?
the binding of one ligand to a protein altering it’s affinity for subsequent ligands
why can haemoglobin be used to transport oxygen?
because it undergoes structural transition from T to R (low-affinity to high-affinity) therefore would be able to bind and dissociate with oxygen
what happens during phase 1 oxidation of drug metabolism?
- oxygen atom is added using cytochrome p450 enzyme.
- NADH, NADPH and O2 required as cofactors
how does cytochrome p450 enzyme bind to oxygen?
contains a haem group so binds using that
what is an iron containing porphyrin?
-4 pyrrole rings joined by one carbon bridge, containing Fe2+ at its active site.
explain how cytochrome p450 works in drug metabolism?
- CYP450 bound to Fe3+
- drug binds to CYP450Fe3+ complex
- NADPH and a reductase enzyme release electrons to reduce Fe3+ to Fe2+
- Oxygen is added and binds to Fe2+ in a linear way and Fe3+ created
- Another oxygen added via NADPH or NADH and reductase enzyme
- Fe3+ binds to O2 in trigonal planar structure
- Proton added and H2O released
- Drug also leaves oxidised into an alcohol
- cycle repeats.
what are the disadvantages of too much iron?
- can cause damage to tissues
- catalyses conversion of H2O2 to free radical ions which attack cell membranes, DNA and proteins
- cardiac toxicity
what is iron deficiency?
- reduces levels of systemic iron conc.
- isn’t a diagnosis, require a diagnosis on the cause of iron deficiency
