biologi molekuler-3 bab2 2013-14
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Biologi Molekuler-3 Bab2 2013-14TRANSCRIPT
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Biologi Molekuler Medik:
“Membran Biologi”Prof. Dr. M. Nurhalim Shahib, dr
Biochemist & Molecular BiologistPascasarjana IKD FKUP
2013
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Struktur dan Fungsi Membran1. Membran merupakan suatu pembatas fisik sel
atau pembatas bagian-bagian sel yang dapat mempertahankan bentuk dan kompartemental seluler
2. Strukturnya memungkinkan terjadinya transpor molekul-molekul tertentu baik dari luar ke dalam sel maupun dari dalam ke luar sel serta proses transpor dari suatu kompartemen ke kompartemen lainnya di dalam sel.
3. Membran dapat menjadi tempat media penghantar sinyal kimia atau energi dari satu bagian ke bagian yang lain.
4. Membran mempersiapkan lingkungan yang optimal bagi berlangsungnya proses biokimia di dalam sel.
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Komponen biomembran dan fungsinya
Gambar 1 Struktur membran eritrosit.Berbagai macam protein membran di antara fosfolipid (Sumber: Van Gelder, et al., 2003).
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1) Lipid
Gambar 2 Struktur umum fosfolipid.
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Gambar 3 Struktur kimia fosfolipid yang terdiri dari bagian polar dan nonpolar.
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H3+N – CH2 – CH2 – O – P – O – CH2
O-
OHC – O – C -
O
HC – O – C -
O
Ekor (hidrofobik)
Etanol amin
Bagian kepala (hidrofilik)
Gambar 4 Struktur fosfoetanolamin.
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Gambar 5 Ikatan fosfolipid dengan kolesterol pada membran biologis. Di sini terlihat bahwa kolesterol berada di antara molekul fosfolipid (a), yang dijelaskan dengan struktur kimia b).
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Gambar 6 Mobilitas molekul fosfolipid membran. Skema pergerakan fosfolipid. Tiga macam pergerakan difusi lateral, seperti pada skema (i), ii) dan iii) (Sumber: Membrane Dynamic)
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Gambar 7 Bentuk lipid membran yang berkaitan dengan sifat fluiditas.
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2) Karbohidrat3) Protein
Gambar 8 Macam dan mobilitas protein. Macam protein menurut letaknya, perifer dan integral.Mobilitas protein, dapat berupa rotasi dan bergerak ke arah lateral
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Membran Potensial dan Bioelektrik
Gambar 9 Pengukuran potensial elektrik melalui membran sel syaraf.Satu elektroda di dalam sel yang lainnya di luar sel (di dalam media).
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Gambar 10 Transpor ion melalui membran sel neuron. Terdapat empat macam jalur ion. Resting channel yang selalu terbuka; voltage-gated channel; ligand gated channel dan signal-gated channel (Darnell J. et al., 1990).
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Jenis Transpor Biomembran
1. Arah pergerakan molekul terhadap molekul lain
Gambar 11 Skema unipor, simpor, dan antipor (Sumber: Alberts, B. et al., 1983)
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2. Keperluan energi
Gambar 12 Skema transpor pasif dan aktif (Sumber: Alberts, B. et al., 1983)
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Gambar 13 Skema transpor melalui kanal pada biomembran. Gambar 50a, adalah ligand-gated channel sedangkan 50b, adalah voltage-gated Channel (Sumber: Alberts, B. et al., 1983, dengan sedikit modifikasi)
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3. Fisiko-kimiaa) Difusi sederhana
Gambar 14 Kurva tranpor difusi sederhanaV=laju transpor, S=kadar substrat, K=Konstanta difusi
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Gambar 15 Substrat melalui antar molekul fosfolipid.
= Substrat (S)
Gambar 16 Substrat lewat pori. Kriteria molekul : besar molekul & muatan molekul
= Substrat
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b) Transpor pengemban
c) Transpor campuran
Gambar 17 Skema transpor zat dengan perantara pengemban.
Gambar 18 Transpor campuran dibandingkan dengan difusi.
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d) Transpor dengan Vesikel (Endositosis dan Eksositosis)
Gambar 19 Skema transpor vesikel.A = proses endositas; B = proses eksositas; m = membran; v = vesikel
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Gambar 20 Endositosis dan eksositosis pada mukosa usus (Darnell J. et al., 1990)
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Transpor Glukosa pada Eritrosit
Gambar 21 Transpor glukosa pada eritrosit. Merupakan transpor facilitated diffusion dan Gerakan glukosa dari luar ke dalam sel.
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Transpor Glukosa pada Usus Halus
Gambar 22 Transpor glukosa dari lumen usus ke dalam darah. (Darnell J. et al., 1990)
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Transpor H+ pada Lambung
Gambar 23 Proses pengasaman lumen lambung oleh sel parietik. (Darnell J. et al., 1990)
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Kegunaan Medik Studi Transpor Biomembran
1. Meningkatkan Efektivitas Obat2. Membantu Menerangkan Mekanisme Kerja Racun
(Toksin)3. Membantu Mengevaluasi Pertumbuhan Organisme4. Membantu Melindungi Tubuh Terhadap Infeksi
Gambar 24 Kinetika hambatan asam bongkrek pada transpor glukosa (metode Lineweaver-Burk). y = tanpa asam bongkrek, y’ = dengan asam bongkrek
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Gambar 25 Penyerapan nutrien oleh sel X = jumlah nutrien di luar sel, Xi = jumlah nutrien yang diserap. Xpool = jumlah timbunan nutrien di dalam sel, P = pengemban
(Carrier)
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Penerapan PCR dan RFLP untuk Mengetahui Kelainan Glucose Transpoter pada Eritrosit
Gambar 26 Model membran transport.
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Gambar 27 Kinetika transpor biomembran.(a) Kinetika transport V terhadap [S](b) Kinetika transport 1/V terhadap 1/[S]
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Gambar 28 Kurva transpor menurut Hofstee.
Gambar 29 Posisi annulus pada membran lipid. = annulus lipid
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1. Proses absorbsi makanan/ nutrien pada saluran pencernaan
2. Proses sekresi dan reabsorbsi pada ginjal3. Proses transpor nutrien pada plasenta4. Proses transpor nutrien pada eritrosit5. Pengaruh obat, inhibitor atau pun racun
terhadap proses transpor6. Pengaruh lingkungan dan aktivator terhadap
transpor nutrien7. Penetrasi obat dan bahan kimia lain
04/28/2008 29
Radio aktif
Dikembangkan tanpa radio aktif
TRANSPOR NOTRIEN MELALUIMEMBRAN SEL TANPA RADIOAKTIF
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04/28/2008 30
t
pH
Glukosa dalam NaCl 0,9%
Penentuan kadar zat yang
ditranspor
0 1 2 4
waktu (menit)
V
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04/28/2008 31
Waktu transport sangat cepat
15” (detik)
Afinitas trasnporter nutrienMerupakan intipermasalahan
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04/28/2008 32
glukosa
Transporter ( Glut I )
Ca+
Media glukosa
eritrosit
Eritrosit (RBC)
- Kit Diagnostik
- Reagent Pemeriksaan Lab
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CH3
CH3
SH SH
Protein Membran
Ca+
Ca+/K+/Na+
Nutrien
Inti sel
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CH3
CH3
SH S-S
Ekstra seluler
CH3
Glukosa
Glukosa
HB (Asam bongkrek)
Hg++
Protein rusak
Transpor zat terhenti
Intra seluler
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Nutrien
Nukleus
?
R
Toxin
DNA/ Gen
EnzimReseptorTransporter
H
mRNA
Pengembangan marker molekuler
Membran sel
• Diagnosa dini kelainan transporter
• Bahan alam untuk “gene expression”
• DNA profile (prokariot dan eukariot)
• DNA finger printing
•Glut•Na+/K+ - ATPase
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Komposisi larutan stopper Proses transpor 15’ (detik) Volume sel
Substansi yang Dipatenkan pada Transpor Biomembran
Novelty Langkah
inventif Indrustri
Landasan kit diagnostik Landasan pemeriksaan
klinis Landasan pemeriksaan
laboratorium untuk research
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1) Anemia- Volume of cells- Cell surface - Number of transporters
2) Cancer- Metabolism- Number of cells
3) Infertility- Spermatozoa disorders
Clinical Application
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4). All cases related to carbohydrate metabolism and energy imbalance5). Studies of glucose transport in human skeletal muscle Method : Biopsy6). Glucose transport and another micronutrients
In human during critical Ilness (e.g. sepsis, injury) and chronical diseases such as diabetes, obesity, hypertension, starvation.
Methods : - erytrocyte
- leucocyte
- tissues
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7). Monitoring the function of membrane transport related to endocytosis as a fundamental cellular processes
8). Membrane transport in reproductive medicine- Disease of placentae - Low birthweight
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10). Neurodegerative disease dysfunction of - Progressive memory loss - decline in cognitive abilities
ion channel or pumps : - pottasium channel - calcium channel - Na+ / K + - ATPase
9). Genetik disorders of Membrane transport (copper transport) Wilson’s disease and Menkes disease Methods : prokaryotic and eykaryotic cells
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11). Kelainan ekspresi gen transporter
methods : - CNS - feripheral cells - or tissue
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2,5 5 7,5 10 12,5 15
Vmax
½Vmax
Km
V
[ s ]
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Gambar. Kinetika transport nutrisi melaui membran sel
V = K [ s ] a (simple diffusion)
[ s ]
Vmax
V
a
b
cd
V = b (facilitated diffusion) Vmax [ s ]
Kmax [ s ]Km (b) < Km (c) < Km (d)
Normal < kelainan transports < kelainan membran (transporter + nontransporter)
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terimakasih