HEMOGLOBIN

dan
MIOGLOBIN

Oksidasi bahan makanan

merupakan tahapan penting dalam penyediaan
energi bagi sel.
oksidasi glukosa oleh oksigen menghasilkan
energi 18 kali lebih besar daripada tanpa
oksigen.
Mekanisme pemasok oksigen pada vertebrata
1. Sistem peredaran darah
2. Molekul pembawa oksigen
untuk mengatasi rendahnya kelarutan oksigen
dalam air.
pada vertebrata: hemoglobin dan myoglobin.

Hemoglobin
terdapat dalam sel darah merah,
pembawa oksigen dalam darah
Fungsi:transport karbon dioksida dan
ion hydrogen.

Mioglobin
terdapat di otot,
menyediakan cadangan oksigen dan
mempermudah pergerakan oksigen di otot.

Hemoglobin
(human, adult )
- heterotetramer,
()2
-heme &globin
- each subunit of
Hb is a globular
protein with an
embedded heme

HEME (Feroprotoporphyrin)
Terdiri

dari protoporphyrin IX dan Fe

Terikat pd polipeptida Hb/Mb via ikatan hidrofob
Memiliki pocket pengikat O2, CO2, H2O
Koordinasi pengikatan tiga molekul tsb dijelaskan
oleh Bohr (Efek Bohr)
Afinitas CO pada Hb > daripada 3 molekul tsb,
sehingga gas CO dapat memblok pengikatan O2
pada Hb sangat toksik
Pada Hb
: Fe(II)
MetHb : Fe(III)
Oksidasi Fe(II) menjadi Fe(III) oleh O2 dihalangi
oleh bagian hidrofob pada struktur Hb maupun
Mb MetHb/MetMb sukar terbentuk

http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg

Myoglobin and Hemoglobin Structure

Glu6-Val6
oxyMb (MbO2)

oxyHb (HbO2)

deoxyMb

O2

O2
O2
O2

O2

Glu6-Val6

Hb Heme Center Changes

A heme group
-consists of a porphyrin (ion Fe dalam cincin heterosiklik)
-Ion Fe (octahedral group of six ligands):
merupakan sisi pengikat oksigen
berikatan koordinasi dg 4 N (pusat cincin)
berikatan dg protein globular via cincin
imidazole pada residu F8 histidine
(di bawah cincin porphyrin).
posisi ke 6 mengikat oksigen (reversibel)
Oxygen binds in an "end-on bent" geometry where one oxygen
atom binds Fe and the other protrudes at an angle.
When oxygen is not bound, a very weakly bonded water

HEMOGLOBIN
The main pocket of
each chain is occupied
by the heme group
which is essential for
function.
Mutations in these
pockets might interfer
with heme binding and
thus oxygen transport.

Efek Bohr
Rapidly metabolizing tissues (contracting muscle):
have a high need for O2
generate large amounts of H + and CO2
(heterotropic effectors enhancing O2 release)

The O2 affinity of Hb decreases as pH

decreases from the value of 7,4 found in the
lungs (fig)
The regulation of O2 binding by H+ and CO2 is
called Bohr effect (Christian Bohr, 1904)

Faktor yang mempengaruhi pengikatan O2

Depends on pH ([H+]), CO2, BPG (DPG), Temp

pH
BPG or T
left shift

pH
BPG or T
right shift

Factors that Modify Hb Transport

Bohr effect: pH causes O binding -releasing it
of Oxygen
2

DPG O2 binding (response to high altitude)

PCO2 decreases O2 bindingreleasing it
(Temperature affects the curve but doesn't vary in
humans)
2,3

Factors that Modify Hb Transport

of Oxygen

Figure 18-9: Physical factors alter oxygen binding to hemoglobin

Review of Respiratory
Exchange & Transport

Figure 18-14: Summary of gas transport

Fetal Hemoglobin

The oxygen saturation curve for

fetal Hb (blue) appears left-shifted
when compared to adult Hb (red)
since fetal Hb has a greater affinity
for oxygen.

Globin of fetal Hb is
composed of two alpha
and two gamma
subunits, commonly
denoted as 22.

Molecular and cellular changes HbS

Heme

Val

http://www.sicklecellinfo.net/fiberformation.htm.
Daniel J. Harrington, D. J., K. Adachi, and W. E. Royer, Jr. 1997. J. Mol. Biol. 272(3):398-407

Molecular and cellular changes of hemoglobin S

Basic abnormality - glutamic acid valine at the sixth position of the -globin
chain. heme plus 2 normal -globin and 2 abnormal -globin chains forms HbS.
HbS carries O2 normally but begins to form semisolid aggregate structures
once O2 is unloaded to the tissues. These HbS aggregates distort RBCs and
cause them to lose their normal elasticity.
HbS initially retains its ability to return to its soluble form, and RBCs can regain
their elasticity upon reoxygenation. However, this process harms RBCs, and,
with repeated deoxygenation cycles, permanent RBC damage results. Although
HbS polymerization and RBC sickling under deoxygenated conditions are
central to the pathophysiology of this disease, growing evidence indicates that
SCD is a state of inflammation characterized by vascular endothelium
activation and increased blood cell endothelium interactions. Abnormal
interaction of sickle RBCs with vascular endothelium is considered a key
contributor to the initiation of vaso-occlusion in this disease.
Adhesion of sickle RBCs involves contribution from both sickle RBC
abnormalities (induced by repeated sickling, expression of adhesion molecules,
and dense RBC formation) and up-regulation of endothelial adhesion
molecules. Ischemic and reperfusion events in the microcirculation may lead to
endothelial oxidant generation, endothelial activation, and up-regulation of
adhesion molecules.

http://www.emedicine.com/ped/TOPIC2096.HTM

Effects of therapy with hydroxyurea

http://www.emedicine.com/ped/TOPIC2096.HTM

Reducing the Flexibility of the Main Chain

Stabilization of exposed loop by mutating Gly to Pro
Mutation: G51P

BAHAN DISKUSI BAB I

1. Jelaskan: (a) struktur 3D, (b) sifat amfoter, dan (c) jenis
asam amino
2. Bagaimana tingkatan organisasi struktur yang ada pada
protein.
3. Apakah struktur 3D protein (native protein) penting untuk
menjamin fungsi protein tsb? Contoh?
4. Mengapa polipeptida membentuk struktur sekundernya
(-heliks maupun -sheet). Atau
5. Apa yang menstabilkan pembentukan ikatan sekunder
protein?
6. Uraikan dengan bukti2 bahwa urutan aa menentukan
pembentukan struktur 3D protein
7. Jelaskan peran: (a) chaperon (b) PDI pada
pembentukan struktur 3D.

 Mengapa transport okigen di darah

memerlukan Hb?
Mengapa keberadaan oksigen di otot
juga memerlukan Mb?