Oxygen Transport

What are the problems with oxygen?

it has limited solubility (0.13mM)

What is the solution to this limited solubility?

• transition metals act as oxygen carriers

• reversibly bind to O2

• increase solubility by magnitude of 2

What are oxygen carriers?

binds transport and deliver oxygen to cells and tissues

what are the primary oxygen carriers?

copper and iron

What was the low O2 environments

• Photosynthesis existed but oxygen created is in equilibrium with elements in earths crust

• ie. iron picks up O2

• reductive conditions

• Fe–Fe2+ (bioavailable)

• Cu- Cu+ (insoluble and not bioavailable)

What happened in the great oxidation event

• photosynthesis took off

• the oxygen produced overwhelmed equilibrium

What happened after the GOE

• oxidizing environment

• organisms had to adapt to the new climate and molecules

• Cu- Cu2+ (bioavailable)

• Fe3+- Fe2+ (insoluble and not bioavailable)

• organisms adapted to use Cu2+

What is metal center for hemoglobin

Fe

Biological function of hemoglobin

transport

animals with hemoglobin

verebrates and invertebrates

metal center for myoglobin

Fe

biological function for myoglobin

storage in muscles

vertebrates for myoglobin

vertebrates like mammals, birds, fish etc.

metal center of hemocyanin

Cu2

biological function of hemocyanin

transport

animals with hemocyanin

marine animals like octopus and crabs

hemerthyrin metal center

Fe2

biological function for hemerthyrin

transport and storage

animals with hemerythrin

peanut worms, brachiopods, etc.

³O₂

triplet oxygen

²O₂ ^-

super oxide

^1O₂ ^2-

peroxide

2O₂ -2

oxide

adding hydrogen

creates hydroperoxide, water and hydroxide

Heme binding

• in hemoglobin and myoglobin

• molecules have a heme center for binding oxygen

• binds Fe2+ to give heme

what is a heme

• prosthetic group

• not part of aa sequence

• strongly bound non-protein unit

Porphyrin ring arrangement on metal

• should be planar

• non bonding pairs on nitrogen all lie on the same plane

• only works if metal all fits in the space available

• if metal is too large it will be pushed out of the planar porphyrin ring

• this distorts square planar and planar geometry of the ring

how does o2 and co bind to heme

• favourably

• histidine is the last ligand

• CO binds in a linear end on manner

• O2 has bent end on geometry

What it the magnetism states of oxygenated and oxygenated heme?

• deoxygenated heme is paramagnetic

• oxygentaed in diamagnetic

• only oxygenated can fit in porphyrin ring

Paulings model

• assumption that because iron in ferric Fe3+ state does not bind to oxygen iron must remain in Fe2+ state in both oxygenated and deoxygenated forms

• covalent bonding of O2 as a strong field ligand changed configuration from high spin to low spin making Fe2+ diamagnetic

• 3O2 is paramagnetic

• for oxygenated heme to become diamagnetic O2 must be diamagnetic

• therefore when O2 binds to heme a spin flip occurs to make diamagnetic singlet oxygen

shortcomings of pauling model

• singlet state of oxygen is high in energy and unfavourable

• change from high to low spin only partially account for the reduction in size of Fe

What is the Weiss Model?

• currently the most accepted model

• suggests binding of oxygen is a redox reactions

• when o2 binds Fe2+ is oxidized to low spin fe3+ and O2 is reduced to o₂ - superoxide

• therefore the binding is ionic and the heme in ferric state caries oxygen as a super oxide

• o₂ - binds to Fe3+ but o2 does not

How does weiss model explain diamagentism

• single unpaired electron in Fe3+ and on ein o2- cancels out

• called antiferromagnetic coupling

• able to cancel out since not on the same molecule

• explains why Fe of oxygenated heme fits in ring and is supported by data

Structure of myoglobin

• sperm whales have high concentration in their blood

• single protein molecule so its tertiary final form

• 153-154 aa

• 8 alpha helices A-H

• starts from N terminus

• corners are labelled with two letters corresponding to connected helices

• individual amino acids numbered based on N-terminus sequence

• histidine 64 and 93 important

Proximal and distal histidine

• F8 (93) and E7 (64)

• proximal used to bind heme prosthetic group

• distal does not bind to heme

Distal histidine

• binding of O2 or CO to myoglobin is simple associative equilibrium

• increases affinity for O2 and decreases affinity for Mo than hemolglobin

• KMb-O2 > Kheme-O2

  • due to hydrogen bonding

• KMb-CO < Kheme-CO

  • due to not being spontaneously in range

what reduces CO affinity in myoglobin

• other aa like Val68 (E11)

• added steric hinderance reduces favourability of Co binding not O2

experiments:

• when Val 68 became Ala68 there was little affect on O2 affinity but big on CO affinitiy

• whe Val68 becomes Ile68 bioh O2 and Co affiniuties decrese

• creates a hydrophobic pcoled for oxygen

• co is polar so it gets rejected

oxygen saturation curve of myoglobin

• associative curve

• find daturation Y to be fraction of total myoglobin oxygenated

• using partial pressures of o2 the graph can be redrawn in terms of partial pressures of O2

• myoglobin saturates easily with O2 making it good for oxygen storage in muscles

What is a hill plot

• more important for hemoglobin

• same information but in a straight line

• no cooperation