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Transport Oxygen

O2 CO2

Sedikit larut dalam air: 3.2 mL O2 /1 L
blood plasma
Transporter: protein

Tissue: oxidative metabolism

Electron acceptor
Molecular oxygen : oxidize metal ions,
Iron-containing enzymes dan protein :
iron, Fe(II) atau Fe(I) .
Fe(III) tidak berfungsi

When molecular oxygen encounters an isolated heme molecule, it

rapidly converts the Fe(II) to Fe(III). The oxidized heme binds oxygen
very poorly. Obviously, if this happened to the Fe(II) groups of hemoglobin and myoglobin, the proteins would be less useful as oxygen
carriers. Oxidation of the heme iron is prevented by the presence of the
distal histidine side chain, which prevents the O2 from forming a
linear FeOO bond. The bond between Fe and O2is bent, meaning
that this bond is not as strong as it might be. Weaker oxygen binding
means easier oxygen release. This is an important principle in understanding not only heme chemistry but also the regulation of hemoglobins affinity for oxygen.

Hemoglobin (Hb)
Heme + Globin
Heme: porfirin dengan 4 bh cincin
pirol dan 1 Fe
Globin: protein

Hemoglobin - Myoglobin
Beda pada quaternary structure.
Hemoglobin : tetramer (2 )
Myoglobin : monomer (quaternary
structure tidak ada).
Myoglobin - oxygen lebih kuat dari
Perpindahan Oxygen sirkulasi ke cell
lebih mudah




Heme-globin, (BM:68,000)
4 heme
porphyrin ring : Fe dan globin
Oxygen terikat dengan Fe ( fero)
Hemoglobin (HHgb) asam lemah (K = 1.4 x 10 ;
pKa = 7.85). Oxyhemoglobin (HHgbO 2) asam

(K = 2.5 x 10-7; pKa = 6.6)

Hb diatur oleh H+ dan CO2

Oksi Hb Deoksi Hb
O2 meningkat pada alveoli: Rx
bergeser ke kanan dan ion H
HHgb + O 2 <===> HgbO
2 + H+

Perbahan bentuk Hb
Fe moves in plane,
pulling proximal His
and Helix F

T state (tense) and R state (relaxed) represent two

different conformations of the tetramer
Both bind O2 but R state binds it more strongly

Dissosiasi OksiHb
1. Suhu : afiinitas O2-Hb

2. pH : afiinitas O2-Hb

3. CO2 : afiinitas O2-Hb

Bohr Effect
Competition between oxygen and H +
the effect of pH and CO2 on the binding
and release of oxygen to Hb
Discovered by Christian Bohr
Binding of protons diminishes dioxygen
Binding of dioxygen diminishes proton
Important physiological significance

Carbon dioxide diminishes dioxygen

Hydration of CO2 in tissues and
extremities leads to proton
These protons are taken up by Hb as
oxygen dissociates
The reverse occurs in the lungs


2,3-diphosphoglycerate (2,3,-DPG) : glikolisis anaerob

Afinitas O2-Hb berkurang
Hemoglobin tetramer mengikat satu BPG
BPG stabilizes deoxygenated hemoglobin: BPG ,
afinitas dg O2 sehingga O2 jaringan
Adaptasi High Altitude :
Erytrosit (Hb )

What is special about 2,3-BPG?

Negative charges interact with 2 Lys, 4 His, 2 N-termini

Fetal Hb - lower affinity for 2,3-BPG, higher affinity for

oxygen, so it can get dioxygen from mother

BPG decreases dioxygen binding

affinity of Hb
Preferentially binds to deoxy state
BPG binding to deoxyHb is ionic in
BPG shifts the T R equilibrium
towards the T state
hence lower affinity for dioxygen

BPG in blood normally 5

mM, but it rises at high

Chronic hypoxia triggers an increase

in 2,3-DPG in RBCs
2,3-DPG lowers the binding affinity of
O2 for hemoglobin; this shifts the
curve to the right.
After prolonged exposure to high
altitude, what effect will increased
2,3-DPG have on O2 delivery?

Carbon Monoxide (CO)

Berikatan dengan O2 pada tempat
yang sama
Affinitas: 250 X O2

PCO >0.4 mmHg ; lethal.

Haemoglobin Saturation at High

Permukaan laut : PO2 (100mmHg)
haemoglobin : 98% SATURATED
PO2 < permukaan laut : Afinitas O2Hb saturasi dipertahankan
Tempat tinggi: PO2 (80mmHg),
haemoglobin 95% saturated

Transport CO2
Larut dlm plasma (7 10%, )
Ion bicarbonat:
CO2+ H20 H2CO3 HCO3 + H ion

Berikatan dengan haemoglobin:

CO2 + Hb

Hb sebagai pembawa O2
dan CO2

Fetal Hemoglobin

Increased O2 release to the fetal tissues under

the hypoxic condition.

Chliride shift


This is Fatal

Fe heme : feri (+3)
O2 tidak bisa diikat

Myoglobin binds oxygen

The binding of O2to myoglobin is a simple equilibrium reaction:
Mb + O2 MbO2
Each myoglobin molecule is capable of binding one oxygen,
becausemyoglobin contains one heme per molecule. Even though the
reaction of myoglobin and oxygen takes place in solution, it is convenient to measure the concentration of oxygen in terms of its partial
pressure, the amount of gas in the atmosphere that is in equilibrium
with the oxygen in solution.
The titration curve of myoglobin with oxygen is a hyperbola, as
shown in Figure 6-2 of the form

Small intracellular protein in
vertebrate muscle
Oxygen binding protein
Globular protein
First protein whose structure was
determined by X-ray crystallography
153 residues
8 helices
Heme is tightly wedged in a
hydrophobic pocket between the E
and F helices


Oxygen-binding curve of
myoglobin. Myoglobin is halfsaturated with O2
at an oxygen partial pressure
( pO2)
of 2.8 torr (dashed lines). The
hyperbolic shape of
myoglobins binding curve is
typical of the simple
binding of a small molecule to
a protein. The
background is shaded to
indicate the color change
that myoglobin undergoes as it
binds O2.

Hb sigmoidal (S-shaped
This permits the blood to
deliver much more O2 to
the tissue than if Hb had a
hyperbolic curve with the
same P50

Mb is a monomeric heme
Mb polypeptide "cradles"
the heme group
Fe in Mb is Fe2+ - ferrous
iron - the form that binds
Oxidation of Fe yields 3+
charge - ferric iron
-metmyoglobin does not
bind oxygen
Dioxygen binds as the
sixth ligand to Fe