BIOCHEMISTRY OF HEMOGLOBIN OXIDATION-REDUCTION

A. HEMOGLOBIN FORMATION

Heme : a cyclic tetrapyrrole consisting of

four molecules of pyrrole linked by
methyne bridges absorb visible light
colors heme deep red
Hemoglobin : a tetramer composed of two
different types of subunits

The tetrameric structure of hemoglobin facilitates saturation with O2 in the lungs and release of
O2 as it travels through capillary beds

B. OXYGEN DISSOCIATION CURVES

Myoglobin curve : hyperbolic
Hemoglobin curve : sigmoidal (seperti huruf S)
Interpretation
When Po2 is high (in lungs) both myoglobin and hemoglobin saturated with O2
When Po2 is low (in oxygen-using tissues) hemoglobin cant bind oxygen as well as myoglobin
myoglobin is a good oxygen-storage, hemoglobin is a good oxygen-vehicle
C. OXYGENATION-DEOXYGENATION OF HEMOGLOBIN : CONFORMATIONAL CHANGES
The binding of teh first O2 molecule to deoxyHb
shifts the heme iron toward the plane of the
heme ring from a position about 0.04 nm
beyond it transmitted to the proximal (F8)
histidine rupture of salt bridges between
carboxyl terminal residues one pair of
alpha/beta subunits rotates 15

The cooperativity in O2 binding in Hb comes from conformational changes in tertiary

structure that take place when O2 binds
Conformational changes : changing from a T (tense) state with low affinity for O 2 to an R
(relaxed) state with a high affinity for O2
D. HEMOGLOBIN TRANSPORTS CO2 AND PROTONS TO THE LUNGS
After delivering O2 to the tissue Hb transport CO2 and protons to the
lungs CO2 carries as carbamates carbamate changes the charge on
amino terminals from positive to negative favoring salt bridges
formation
CO2 in venous blood : 15% as carbamate, remain as bicarbonate

The Bohr Effect : hemoglobins oxygen binding affinity is inversely related

to both acidity and to the concentration of carbon dioxide
Protons for the Bohr effect arise from rupture of salt bridge

E. AGENTS THAT AFFECT OXYGEN BINDING

1. 2,3-Bisphosphoglycerate
Formed in red blood cells
 Binds to HB in the central cavity
formed by the four subunits
increasing the energy required for the
conformational changes that facilitate
oxygen binding lowers the affinity
of Hb for oxygen oxygen is readily
bound when Hb contains 2,3-BPG
2. Proton Binding (Bohr Effect)
Binding of protons lowers its
affinity for oxygen
pH of blood decrease as it enters the
tissue (because CO2 produced by
metabolism converted to carbonic
acid)
Dissociation of carbonic acid produce
protons react with several amino
acid residues in Hb conformational
changes that promote the release of
O2
In the lungs, proses diatas terjadi
terbalik. Oxygen berikatan dengan Hb
release protons combine with bicarbonate to form
carbonic acid
In tissues : pH of the blood is low because of the CO2 produced
by metabolism O2 released from Hb
In lungs : pH of the blood is higher because CO2 is being exhaled
O2 binds to Hb
3. Carbon Dioxide
Most of CO2 to the lungs as bicarbonate; some of it (15%)
covalently bound to Hb as carbamate
In the lungs : Po2 is high oxygen binds to Hb and CO2
released