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HEMOGLOBIN

dan

MIOGLOBIN

HEMOGLOBIN 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

Hemoglobin

(human, adult )

Hemoglobin Hemoglobin (human, adult ) - heterotetramer, (αβ) - heme &globin - each subunit of Hb
  • - heterotetramer,

(αβ) 2

-heme &globin

  • - each subunit of

Hb is a globular

protein with an embedded heme

HEME (Feroprotoporphyrin)

HEME

(Feroprotoporphyrin)

Terdiri

Terdiri dari

dari protoporphyrin

protoporphyrin IXIX dan

dan FeFe

Terikat

Terikat pdpd polipeptida

polipeptida Hb/Mb

Hb/Mb via

via ikatan

ikatan hidrofob

hidrofob

Memiliki

Memiliki pocket

pocket pengikat

pengikat OO 22 ,, COCO 22 ,, HH 22 OO

Koordinasi

Koordinasi pengikatan

pengikatan tiga

tiga molekul

molekul tsb

tsb dijelaskan

dijelaskan

oleh Bohr

oleh

Bohr (Efek

(Efek Bohr)

Bohr)

Afinitas

Afinitas COCO pada

pada HbHb >> daripada

daripada 33 molekul

molekul tsb,

tsb,

sehingga

sehingga gas

gas COCO dapat

dapat memblok

memblok pengikatan

pengikatan O2

O2

pada HbHb sangat

pada

sangat toksik

toksik

Pada

Pada HbHb

:: Fe(II)

Fe(II)

MetHb

MetHb

:: Fe(III)

Fe(III)

Oksidasi

Oksidasi Fe(II)

Fe(II) menjadi

menjadi Fe(III)

Fe(III) oleh

oleh OO 22 dihalangi

dihalangi

oleh bagian

oleh

bagian hidrofob

hidrofob pada

pada struktur

struktur HbHb maupun

maupun

Mb MetHb/MetMb

Mb

MetHb/MetMb sukar

sukar terbentuk

terbentuk

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

Myoglobin and

Myoglobin

and Hemoglobin

Hemoglobin Structure

Structure

Glu6-Val6 oxyMb (MbO 2 ) oxyHb (HbO 2 )  deoxyMb  O 2 O 2
Glu6-Val6
oxyMb (MbO 2 )
oxyHb (HbO 2 )
deoxyMb
O 2
O 2
O 2
O 2
O 2
Glu6-Val6

HbHb Heme

Heme Center

Center Changes

Changes

Hb Hb Heme Center Changes

A heme group

-consists of a porphyrin (ion Fe dalam cincin heterosiklik) -Ion Fe (octahedral group of six ligands):

A heme group -consists of a porphyrin ( ion Fe dalam cincin heterosiklik) -Ion Fe (octahedral

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

l

l

fill

h

i

f

i

di

d

h

d

HEMOGLOBIN

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.

HEMOGLOBIN HEMOGLOBIN The main pocket of each chain is occupied by the heme group which is

Efek

Efek Bohr

Bohr

Rapidly metabolizing

Rapidly

metabolizing tissues

tissues (contracting

(contracting muscle)

muscle)::

have

have aa high

high need

need for

for

OO 22

generate

generate large

large amounts

amounts of

of HH ++ and

and COCO 22

(heterotropic effectors

(heterotropic

effectors enhancing

enhancing OO 22 release)

release)

The OO 22 affinity

The

affinity of

of HbHb decreases

decreases asas pHpH

decreases from

decreases

from the

the value

value of

of 7,4

7,4 found

found inin the

the

lungs (fig)

lungs

(fig)

The regulation

The

regulation of

of OO 22 binding

binding byby HH ++ and

and

COCO 22 isis

called Bohr

called

Bohr effect

effect (Christian

(Christian Bohr,

Bohr, 1904)

1904)

Faktor

Faktor yang

yang mempengaruhi

mempengaruhi pengikatan

pengikatan OO 22

Depends on pH ([H + ]), CO 2 , BPG (DPG), Temp

pH BPG or T

Faktor yang mempengaruhi pengikatan O O Depends on pH ([H ]), CO , BPG (DPG), Temp

left shift

pH BPG or T

Faktor yang mempengaruhi pengikatan O O Depends on pH ([H ]), CO , BPG (DPG), Temp

right shift

Factors that

Factors

that Modify

Modify HbHb Transport

Transport

Bohr

Bohr effect:

effect: pHpH  causes

of Oxygen

of

causes  OO

Oxygen

22

binding -releasing

binding

high altitude)

altitude)

-releasing itit

DPG  OO 22 binding

2,3

2,3 DPG

binding (response

(response toto high

PP CO2 CO2  decreases decreases OO 22 binding–releasing bindingreleasing itit

(Temperature

(Temperature affects

affects the

the curve

curve but

but doesn't

doesn't vary

vary inin

humans)

humans)

Factors that

Factors

that Modify

Modify HbHb Transport

Transport

of of Oxygen Oxygen
of
of Oxygen
Oxygen

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

Review of

Review

of Respiratory

Respiratory

Review of Review of Respiratory Respiratory & & Transport Exchange Figure 18-14: Summary of gas transport

Exchange && Transport

Exchange

Transport

Figure 18-14: Summary of gas transport

Fetal Hemoglobin

Fetal

Hemoglobin

Fetal Hemoglobin Fetal Hemoglobin The The oxygen oxygen saturation saturation curve curve for for fetal Hb

The The oxygen oxygen saturation saturation curve curve for for fetal fetal HbHb (blue) (blue) appears appears left-shifted left-shifted when when compared compared toto adult adult HbHb (red) (red) since since fetal fetal HbHb has has aa greater greater affinity affinity for for oxygen. oxygen.

Globin of fetal Hb is

composed of two alpha

and two gamma

subunits, commonly

denoted as α 2 γ 2 .

Molecular and

Molecular

and cellular

cellular changes

changes HbS

HbS

Molecular and Molecular and cellular cellular changes changes HbS HbS Heme Val http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington,
Molecular and Molecular and cellular cellular changes changes HbS HbS Heme Val http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington,
Molecular and Molecular and cellular cellular changes changes HbS HbS Heme Val http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington,

Heme

Val

Molecular and Molecular and cellular cellular changes changes HbS HbS Heme Val http://www.sicklecellinfo.net/fiberformation.htm. Daniel J. Harrington,

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

Molecular

and cellular

cellular changes

changes of

of hemoglobin

hemoglobin SS

and Molecular cellular changes of hemoglobin SS Basic abnormality - glutamic acid  valine at

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 O 2 normally but begins to form semisolid aggregate structures once O 2 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

Effects

of therapy

therapy with

with hydroxyurea

hydroxyurea

Effects of Effects of therapy therapy with with hydroxyurea hydroxyurea http://www.emedicine.com/ped/TOPIC2096.HTM

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

Reducing the

Reducing

the Flexibility

Flexibility of

of the

the Main

Main Chain

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?