Chemistry of Fe

Question 1

what is the ground state electron configuration of Fe?

Answer 1

1s2 2s2 2p6 3s2 3p6 3d6 4s2

Question 2

what is the electron configuration of Fe2+?

Answer 2

1s2 2s2 2p6 3s2 3p6 3d6 (the 4s2 electrons are knocked off instead of the 3d electrons)

Question 3

what is the electron configuration of Fe3+?

Answer 3

1s2 2s2 2p6 3s2 3p6 3d5 (knocks off 2 from 4s2 and 1 from 3d6)

Question 4

what are the three common structural complex ions formations?

Answer 4

1. octahedral
2. tetrahedral
3. square planar

Question 5

which are more stable, higher or lower oxidation states?

Answer 5

lower oxidation states

Question 6

what are the two categories which ingested iron can be classified into?

Answer 6

1. Iron-bearing haem moiety (contains porphyrin ligand system)
2. Non-haem containing (no porphyrin ligands)

Question 7

how is iron used by the body?

Answer 7

1. in bone barrow to create reticulo-endothelial macrophages which store the iron
2. in muscles (in their myoglobin)

Question 8

Where is iron mainly stored in the body?

Answer 8

liver parenchyma and reticulo-endothelial macrophages

Question 9

what 4 main body homeostasis are controlled by Fe?

Answer 9

1. metabolism
2. oxygen transport
3. energy generation
4. oxygen transfer

Question 10

what is the structure of a metallo-protein?

Answer 10

• metal complex in crevice of the protein

- some ligands attached to metal are from the protein (if not all the ligands)

Question 11

what decides the geometry of the metal bond angles and distances?

Answer 11

the protein unit it attaches to

Question 12

what is a co-factor?

Answer 12

A non-protein chemical compound bound to a protein and is required for the protein’s biological activity

Question 13

what are the 4 categories for cofactors?

Answer 13

• organic
• inorganic
• coenzymes
• prosthetic groups

Question 14

what is the difference between coenzymes and prosthetic groups?

Answer 14

• coenzymes are loosely bound to an enzyme,

- whilst prosthetic groups are tightly bound.

Question 15

what are protoporphyrin IX?

Answer 15

organic compounds not soluble in basic water. only exists with its iron complex in nature, can’t be found on it’s own.

Question 16

What are haem’s?

Answer 16

prosthetic groups in haemoglobin, myoglobin and cytochrome C

Question 17

what is haemogobin?

Answer 17

• 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

Question 18

what is myoglobin?

Answer 18

• red protein containing haem

- binds to iron to carry (facilitate O2 diffusion) and store oxygen in muscle cells.

Question 19

what is myoglobin made up of?

Answer 19

• a single polypeptide chain of 153 amino acids

- and a single prosthetic group

Question 20

What is the charge of the iron that binds to the haem group on haemoglobin?

Answer 20

Fe2+ (iron in its ferrous state)

Question 21

How many coordination positions does Fe2+ have, and what do they bind to?

Answer 21

• 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.

Question 22

Why must the Myoglobin haem group be kept away from solvents?

Answer 22

Because Fe2+ can easily oxidise to Fe3+ and this doesn’t bind to oxygen

Question 23

During oxygenation of myoglobin, what role does distal Histidine have?

Answer 23

Makes oxygen bind to iron in a bent manner and prevent CO binding in a linear manner

Question 24

what is the amount of oxygen bound a hyperbolic function of?

Answer 24

the amount of oxygen present and the affinity of myoglobin for oxygen

Question 25

Haemoglobin transitions between 2 conformational states depending on whether O2 is present or not. What are these states?

Answer 25

R state (relaxed) and T state (tensed)

Question 26

What state is favoured by O2 binding?

Answer 26

the R state. T state is more stable in the absence of oxygen

Question 27

what happens when O2 binds to Hb in the T state?

Answer 27

triggers a change in the conformation to the R state

Question 28

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?

Answer 28

the His C3 and Lys C5 bonds

Question 29

what is the effect of oxygen on the porphyrin ring and the haemoglobin helix?

Answer 29

promotes flattening of the porphyrin ring | and causes a shift in the helix

Question 30

why is it that once one oxygen molecule binds to one haem group, the other haem groups can bind to oxygen easier?

Answer 30

because that polypeptide changes from T to R state therefore pockets of haem are easier to access due to weak interactions being broken

Question 31

why can't myoglobin be used as an oxygen transporter round the body?

Answer 31

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

Question 32

what is cooperative binding?

Answer 32

the binding of one ligand to a protein altering it's affinity for subsequent ligands

Question 33

why can haemoglobin be used to transport oxygen?

Answer 33

because it undergoes structural transition from T to R (low-affinity to high-affinity) therefore would be able to bind and dissociate with oxygen

Question 34

what happens during phase 1 oxidation of drug metabolism?

Answer 34

- oxygen atom is added using cytochrome p450 enzyme. | - NADH, NADPH and O2 required as cofactors

Question 35

how does cytochrome p450 enzyme bind to oxygen?

Answer 35

contains a haem group so binds using that

Question 36

what is an iron containing porphyrin?

Answer 36

-4 pyrrole rings joined by one carbon bridge, containing Fe2+ at its active site.

Question 37

explain how cytochrome p450 works in drug metabolism?

Answer 37

1. CYP450 bound to Fe3+ 2. drug binds to CYP450Fe3+ complex 3. NADPH and a reductase enzyme release electrons to reduce Fe3+ to Fe2+ 4. Oxygen is added and binds to Fe2+ in a linear way and Fe3+ created 5. Another oxygen added via NADPH or NADH and reductase enzyme 6. Fe3+ binds to O2 in trigonal planar structure 7. Proton added and H2O released 8. Drug also leaves oxidised into an alcohol 9. cycle repeats.

Question 38

what are the disadvantages of too much iron?

Answer 38

- can cause damage to tissues - catalyses conversion of H2O2 to free radical ions which attack cell membranes, DNA and proteins - cardiac toxicity

Question 39

what is iron deficiency?

Answer 39

- reduces levels of systemic iron conc. | - isn't a diagnosis, require a diagnosis on the cause of iron deficiency