Hemoglobin (Hb)

Hemoglobin (Hb)

1. Occupies nearly all of the space in Red Blood Cells

2. Is a tetramer with pairs of alpha and beta dimers that consists of a porphyrin ring with Fe2+ bound in the middle. Fe2+ binds oxygen on one side and binds a protein on the other

3. ** IS AN EFFICIENT TRANSPORTER OF OXYGEN**

   • Binding of Oxygen
     • DEOXYGENATED Hemoglobin: TENSE (TED)
       • LOW O2 Affinity
         • DPG Binds
     • OXYGENATED hemoglobin: RELAXED (ROXY)
       • HIGH O2 Affinity
         • NO DPG bound
     • Promoted conversion of hemoglobin from tense state to relaxed state.
       • The dominate effect when converting from TED to ROXY is the LARGE NET LOSS of salt bridges and hydrogen bonds, causing the central cavity between alpha and beta dimers to shrink
     • KNOW: 1. Oxygen binds to Beta 2 (B2), which pulls on the heme; 2. the heme then pulls on the F-helix, breaking the bond between VAL 98 C=O and TYR 145 O-H, both located on B2 and therefore breaking the hydrogen bond; 3. hemoglobin shifts to the relaxed (ROXY) state
     • Oxygen Binding Curves:
       • Sigmoidal in shape (efficient transport)
         • Normal curve:
         • Weak sigmoidal curve indicates TENSE (TED) state (low affinity for oxygen):
         • Strong sigmoidal curve indicates RELAX (ROXY) state (high affinity for oxygen):
     • Binding in fetuses and adults:
       • Adults: two alpha and two beta subunits
         • HIS 143 in adult transforms to:
           • SERINE in feta gamma
       • Fetuses: Two alpha and two gamma subunits
         • Promotes net transfer of oxygen from mother to baby
           • Increases oxygen affinity

4. Carbon Monoxide (CO) Poisoning

   • CO binds to Oxygen sites on Hemoglobin
     • Has a HIGH K-assoc. causing it to irreversibly bind
     • Hemoglobin binds 50% oxygen and 50% CO
     • Causes hemoglobin to be in the relaxed- TIGHT state (breaks salt bonds) and does not allow change to tense state
       • Oxygen CANNOT unbind from hemoglobin
         • Hangs onto Oxygen at muscles, causing LOW transport
   • NONCOOEPRATIVE, IRREVERSIBLE BINDING, HIGH AFFINITY, LOW EFFICIENCY OF TRANSPORT

5. DPG/DBG Binding

   • Weaker oxygen binding= lower affinity= better transport efficiency
     • Binds in the pocket of DEOXY (TED) hemoglobin
       • Less oxygen binds to hemoglobin
         • Magnitude is LOWER in the lungs (small, bad effect)
         • Magnitude is LARGER in muscles (large, good effect)
           • • Causes an INCREASE in Transport efficiency
   • Oxidized form of glycerol; binds to hemoglobin; HIGHLY negative

6. Bohr Effect

   • Loss of H+ due to CO2 consumption
     • [H] down; pH UP
     • NH+ dissociates due to pH rise
       • Promotes ROXY state
         • Favors O2 binding
           • Strongly (TIGHT) bonds O2
     • HIS DEPROTONATES
   • Shifts binding curve to LEFT