Globular proteins

• Compact proteins that are approximately spherical in shape

Hemoproteins

• Specialized proteins that have prosthetic heme group

Prosthetic groups

• Non-protein molecules that are essential to biological function

HEME GROUP STRUCTURE

• Porphyrin ring with iron center (Fe2+)

Fe2+ coordinates 6 bonds:

• 1-4. Four planar nitrogen atoms (of porphyrin ring)
  5. Proximal histidine
  6. Oxygen

MYOGLOBIN

• Skeletal and cardiac muscle
• Reservoir for oxygen
• Single polypeptide with 8 alpha helix segments
• One heme group
• Distal histidine holds oxygen in place

HEMOGLOBIN

• Red blood cells
  – Supplies body’s tissues with oxygen
• 4 polypeptides (instead of one): each subunit resembles myoglobin structure
  – Tetramer: with 2 alpha-beta dimers
• Strong hydrophobic interactions: stabilize alpha-beta dimer
• Weak ionic and H-bonds: between dimers

T-form hemoglobin

• “Taught” or “tense” form: polypeptides restricted in movement
• Deoxygenated form: oxygen affinity is low

R-form hemoglobin

• “Relaxed” form: weaker ionic and H-binds between dimers
• Oxygenated form: oxygen affinity is high

COOPERATIVE BINDING

• Conformational change between T-form and R-form hemoglobin
• Myoglobin does not exhibit cooperative binding: only one oxygen binding site
  – One oxygen binds hemoglobin subunit
  – Binding disrupts inter-dimer bonds: causes conformational change
  – Change in 3D structure increases oxygen affinity of remaining subunits

DISSOCIATION CURVE

• % oxygen saturation vs. oxygen partial pressure (torr)
• Cooperative binding produces sigmoidal binding curve
• pO2 in body’s tissues: 30 torr
• pO2 in lungs: 100 torr

Hemoglobin

• Half saturated at 30 torr (body’s tissues): responds to O2 availability

Myoglobin

• Hyperbolic curve (simpler binding pattern corresponds to single heme)
• High affinity for O2
• Binding properties correspond to role in oxygen in storage (not oxygen delivery)
• Early curve: exercising muscle; plateau: muscle at rest

CLINICAL CORRELATION

Fetal hemoglobin

• Dissociation curve to the left of adult hemoglobin
• Greater affinity for O2: O2 transfer from maternal hemoglobin to fetus