Porphyrin Heme = Fe + porphyrin ring

Heme

Heme A Heme B Heme C

Mitochondria - cytochrome c oxidase - electron transport

O2

Heme = Fe + porphyrin ring – carry O2

Fe2+ located

Most abundant Hemoglobin and Myoglobin

Mitochondria - cytochrome c - electron transport

Fetal Hemoglobin (2α22γ2)

Human Hemoglobin (2α2 2β2)

Sickle cell Hemoglobin (2α22βS

2) Myoglobin 1 α chain

Carbaminohemoglobin Carboxyhemoglobin Oxyhemoglobin

Porphyrin Ring

Porphyrin are ligand bind metal to form complexes Heterocyclic ring contain Carbon/Nitrogen

Form a chelate with metal

Porphyrin containing metal Fe – heme Hemoglobin and myoglobin contain iron porphyrin

Heme

Hemoglobin - 4 chain - 4 heme (porphyrin) - 4 Fe 2+

Fe 2+

Heme (porphyrin)

Hemoglobin - 2 alpha chain - 144 amino acid - 2 beta chain - 146 amino acid

O2 add to Fe as sixth ligand O2 tilt relative to perpendicular of heme plane

His E7 locate over Fe, force CO to bind to Fe at an angle. Steric hinderance reduce afinity of CO in hemoglobin. O2 bind to Fe at an angle, its binding not affected by presence of His E7.

His (E7)

His (F8)

vs

Myoglobin - 1 chain – 1 heme - 1 Fe2+

- 154 amino acid

Hemoglobin Myoglobin

Fe 2+

Heme (porphyrin)

His (F8)

His (E7)

C≡O

Heme

Hemoglobin - 4 chain - 4 heme - 4 Fe 2+

Fe 2+

Heme (porphyrin)

Hemoglobin - 2 alpha chain - 144 amino acid - 2 beta chain - 146 amino acid

Myoglobin - 1 chain – 1 heme – 1 Fe2+

– 154 amino acid

Hemoglobin Myoglobin

Fe 2+

Heme (porphyrin)

Fe in cytochrome 1 polypeptide chain

Fe 2+

Cytochrome c

Bind O2 reversibly/ weak bond Fe2+ bind to O2 (oxygenated )

Hemoglobin + O2 = Oxyhemoglobin

Binding O2 is cooperative binding ↓

Conformational shift caused by binding of O2 at one heme ↓

Makes other heme more receptive More O2 bound to hemoglobin

↓ All 4 binding sites are saturated

% Hb saturation with O2 sigmoidal "S-shaped"curve

Oxygen dissociation curve (ODC)

P50 = partial pressure when hemoglobin 50% saturated O2.

cooperative binding

Hb load/unload O2 reversibly

Hemoglobin

% Hb saturation with O2 sigmoidal "S-shaped"curve

Oxygen dissociation curve (ODC)

P50 = partial pressure when hemoglobin 50% saturated O2.

Factor influence Hb affinity O2

Hb + 4O2 ↔ Hb (O2)4

Shift to right – reduced affinity

↑ Increase temp ↑ Increase pCO2

↓ Decrease pH

Shift to left – increase affinity ↓ Decrease temp ↓Decrease pCO2

↑ Increase pH

cooperative binding

At lung at high O2 conc

% saturation Hb increase

Tissue/muscle at low O2 conc

% saturation Hb drop unloading O2 to tissue

% saturation Hb

pO2

O2 released to tissue

% saturation Hb

pO2

At tissue at high CO2 conc

Shift to right – less affinity % saturation Hb decrease

CO2 ↑

5

98%

48%

50%

pO2 5kPa

48%

88%

At normal % saturation Hb

40% O2 released/unload

to tissue

Hemoglobin

Oxygen dissociation curve (ODC) Factor influence Hb affinity O2

Shift to right – reduced affinity

↑ Increase temp ↑ Increase pCO2

↓ Decrease pH

Shift to left – increase affinity ↓ Decrease temp ↓Decrease pCO2

↑ Increase pH

% saturation Hb

pO2

sigmoidal cooperative

binding

hyperbolic

Myoglobin/Foetal ↓

Shift to left ↓

Higher affinity

Cytochrome responsible for ATP production In electron transport (redox rxn)

Heme conjugated ring system (elec mobile) Iron in form of Fe2+/Fe3+

Heme in cytochrome undergo reversible elec transfer Fe3+ (oxidized) ↔ Fe2+ (reduced)

Foetal/Hemoglobin/Myoglobin

Cytochrome c

Fe in cytochrome in Fe2+/3+

1 polypeptide chain

Fe 2+

Heme = Fe + porphyrin ring

Hemoglobin Fe + porphyrin ring

Chlorophyll Photosynthetic pigment Mg + porphyrin ring

Hemoglobin vs Chlorophyll