TRANSPORTER SEBAGAI TARGET AKSI OBATPengantar: Tinjauan Membran Sel

15 October 2012

The Cell Membrane

Cell Membrane:

At Very High Magnification & in color

Membrane Structure

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.html

Protein membran• Integral: embedded within bilayer

• Peripheral: reside outside hydrophobic region of lipids

Protein membran…. cont.

Text pg 80

How to get other molecules across membranes??

Mekanisme transport membran

I. Passive Transport

• Difusi- perpindahan substansi (molekul) dengan turunnya gradien konsentrasi dari daerah dengan konsentrasi molekul tinggi ke daerah konsentrasi rendah

• Difusi terfasilitasi- tipe passive transport yg menggunakan bantuan transport proteins/ carrier proteins

• II. Active Transport– Menggunakan bantuan ATP

The membrane lipid barrier:Passive diffusion through the lipid bilayer

• Concentration gradient up, diffusion up• Molecule lipid solubility up, diffusion up• Molecular size up, diffusion down• Molecule electrically charged, diffusion blocked

• Transport proteins Transports molecules or ions across biological membranes

• 3 types of transport proteins:1. uniport 2. symport 3. antiport

UNIPORT SYMPORT ANTIPORT

Uniport Transport Protein

extracellularfluid

intracellularfluid

Carries a single solute across the membrane

Ex: Transporter glukosa GLUT1; Transporter GABA; Transporter kolin

Symport Transport Protein

• Translocate 2 different solutes simultaneously in same direction.

intracellularfluid

extracellularfluid

Ex: simport glucose Na+; simport Na+/Cl-

Antiport Transport Protein EXCHANGER (Countertransporter)

• Exchanges 2 solutes by transporting them in opposite directions.

intracellularfluid

extracellularfluid

Ex: ADP/ATP Exchanger; diffusion anion antiporter in red blood cells

Membrane Transport MechanismsII. Active Transport

• Active transport- The movement of molecules (small or large) across the plasma membrane & against concentration gradient in which energy (ATP, PEP, light energy, electron transport) is required.

• Examples: ATP-powered Ion pump

1. Sodium (Na) - Potassium (K) Pump Na+/K+ ATPase2. Pump Ca2+3. K+/H+ ATPase di sel parietal lambung

Sodium-Potassium Pump• The mechanism that uses energy (active

transport) released from splitting ATP to transport Sodium (Na+) out of and Potassium (K+) into cells.

The Na+ - K+ pump cycle

HOW THE MECHANISM??

The glucose uniporter transports glucose across membranes

• Ligand (glucose) binding flips the transporter to a different conformation (changes shape)

• The new conformation releases glucose on the other side of the membrane

• Release allows it to flip back to repeat the cycle

Glucose Transporter:How it works..(on the other scheme)

• glucose binds to outside of transporter (exterior side with higher glucose conc.)

• glucose binding causes a conform. change in protein

• glucose drops off inside cell

• protein reassumes 1st configuration

How carrier proteins change conformation

The ligand bindingsite is exposed onthe upper membranesurface

The folding pattern flips to a different position

The ligand bindingsite is now exposed onthe lower membranesurface

The carrier isnow ready totransport anothermolecule

Without the ligand bound, conformation returns to the first state

Facilitated diffusion anion antiporter in red blood cells (RBC)

• Multipass protein that binds to spectrin• Exchanges Cl- for HCO3

-

• Important for transporting CO2 to the lungs

Facilitated diffusion anion antiporter in red blood cells

• When the bicarbonate diffusion gradient is reversed, the process reverses

Why HCO3- for CO2?Why antiport Cl-?

TRANSPORTER SEBAGAI TARGET AKSI OBAT

Hidrophilic Agent Transporter (Uniport)1

SIMPORT/Co-transporter Contoh obat: - Tiazid : simport Na+/Cl- pada

Tubulus distal - Furosemid: simport Na+/K+/2Cl-

pada Loop Henle

2

THE NEPHRONGlomerulus Bowman’s capsule Proximal convoluted tubule

Loop of Henle: descending, ascending Distal convoluted tubule collect. tubule

Mekanisme aksi Thiazide

1

Mekanisme Omeprazole

2