Cell membrane, ABC transporters, membrane transport systems

Cell membrane structure

40-60% lipid, 30-50% protein, 10% carbohydrate

5-8nm thick

Asymmetry important for cell signalling

Cell membrane function

To surround and separate the extracellular matrix and the intracellular matrix.

Establishes connections between the extracellular matrix and the intracellular matrix and other cells (signal transduction, transport, cell adhesion)

Passive transport

Smaller, hydrophobic molecules diffuse across a concentration gradient

Facilitated diffusion

Diffusion via protein channels

Does not directly require ATP

Facilitated diffusion is characterized by:

High rate of transport compared to simple diffusion

Channel saturation leading to decreased transport

Specificity

Competition

Temperature

Inhibition by drugs

Active transport

Movement of molecules against a concentration gradient

Requires ATP

ABC transporters (ATP binding casette)

Transmembrane proteins found in prokaryotes to humans.

The active transport of hydrophobic molecules through the membrane

Have ATP-binding domains/nucleotide binding domains.

ABC transporter roles

Removal of toxic substances

Secretion of substances produced by cell

Uptake of substances (metabolites, lipids, steroids, medicines)

ABC transporter classifications

Pumps

channels

ion channel regulators

Structure of P-glycoprotein

2×6 transmembrane helix

2 ABC

Function of p-glycoproteins

Pump out toxins and drugs out of the cell (hydrophobic vacuum cleaner)M

Multidrug resistance

ABC transporters are involved in the removal of xenobiotics from cells and play an important role in the development of multidrug resistance in tumors

Multidrug resistance causes

P-GP

MRP1

BCRP

To increase effectiveness of tumor therapy

Inhibition of ABC transporters via modulators

Inclusion of cytostasis in liposomes

Medications that cannot be recognized by ABC transporters.

CFTR (cystic fibrosis transmembrane conductance regulator)

Cl- channel gated by ATP hydrolysis

Regulated the operation of Na+ and K+ channels.

Located in the membrane of epithelial cells

Absence causes digestive, respiratory issues and inflammation of glands

SUR1 (Sulfonylurea receptor)

Regulates ATP sensitive K+ channels expressed in the B-Cells of pancreas, regulating insulin secretion