Biochemistry Hemoglobin and Myoglobin

Myoglobin

-Monomer (lacks quaternary structure)

-16.7 Kia

-Binds O2 tightly

-Highly concentrated in muscles and low levels in blood

-O2 supplier for muscle

-alpha-helices and NO beta-sheets

Heme

-Embedded group in protein and needed for function

-4 coordination sites to porphyria sites (N’s)

-5th coordination site is to an H (histidine; amine N)

-6th coordination site is to molecular oxygen (stabilized by another H via H-bond)

Hemoglobin

-64 kDa tetramer (a2B2)

-Each subunit has some amino acid sequence

-Subunits have similar structure overall to each other AND myoglobin

-Binds O2 in cooperative manner - when 1 O2 binds others can bind more easily due to change in structure

-O2 transporter

-High concentration in blood

H146

Forms charge-charge IMF interaction on Beta subunit of hemoglobin

-Deprotonated in HbR state

Shift to HbR (left)

-Low BPG

-High pH

-Low CO2

-Fetal Hb

-CO Poisoning

Shift to HbT (right)

-High BPG

-Low pH

-High CO2

-Altitude Sickness

Fetal Hb

-a2Y2 (alpha2gamma2) instead of a2B2

-Binds O2 stronger than typical adult Hb

-Y (gamma) subunit has S143 instead of an H143 near BPG binding site (Can’t form so BPG doesn’t bind as readily meaning T state is destabilized)

Altitude Sickness

-pO2 is lower so bodies focus on delivering O2 efficiently

-Produce more BPG resulting in more efficient O2 delivery

Carbon Monoxide (CO)

-CO has a higher affinity for O2 than Hb (will not unbind)

-Decreases max amount of O2 saturation

-Trapped in HbR = Very poor O2 delivery

Exercise

-Increased needs for O2 produces ATP

-Our body needs more CO2 (decrease in pH) and metabolizes more BPG

-Shift to HbT BECAUSE of more CO2, decreased pH, and more BPG

Sickle Cell Anemia

-Mutation in Beta subunit that changes from negative to neutral and polar to nonpolar (no conservative mutation)

-RBC’s can rupture that reduces O2 delivery

-Hydrophobic interaction can occur between Hb molecules which can cause aggregation

-Dangerous at high altitudes combines with strenuous exercise