Cystic Fibrosis Mutation Quiz

Membranes and Membrane Transport

• Membranes are a stable yet dynamic barrier maintaining the cell's internal environment.
• They facilitate cellular functions.
• They act as attachment points for intracellular and extracellular structures.
• Membranes maintain a selectively permeable environment.

Basic Structure

• Membranes consist of a phospholipid bilayer.
• The bilayer is composed of two antiparallel phospholipid sheets.
• The layer closest to the cytosol is the inner leaflet.
• The layer closest to the exterior environment is the outer leaflet.
• Cholesterol is interspersed between the phospholipid layers.
• Proteins are associated with the membrane.

Membrane Lipids

• Phospholipids are the most abundant membrane lipids.
• They are amphipathic, meaning they have both polar heads and hydrophobic tails.
• Polar heads point outwards, and hydrophobic tails point inwards.
• The length of the fatty acid chains and their degree of saturation affect membrane structure.
• Fatty acid chains undergo flexion, rotation, and lateral movement.
• Double bonds in fatty acids create kinks, reducing tight packing.
• Phospholipids in healthy cells rarely flip-flop between leaflets.
• Cholesterol is an amphipathic molecule.
• It fits into spaces created by unsaturated fatty acid tails, decreasing their movement and stiffening/strengthening the membrane.

Glycolipids

• Glycolipids are lipids with attached carbohydrate chains.
• The carbohydrate portion points outwards.
• They help form the carbohydrate coat on cells.
• They participate in cell-to-cell interactions.
• They can be a source of blood group antigens.
• They can act as receptors for toxins (e.g., cholera and tetanus).

Membrane Proteins

• Membrane proteins are diverse and have various functions.
• Transmembrane proteins are embedded within the membrane.
• Lipid-anchored proteins are attached to the membrane through lipids.
• Peripheral membrane proteins are associated with the membrane surface.
• These proteins play roles in cell adhesion, ion transport, ligand binding, G protein activation, and cell signaling.

Functions of Membrane Proteins

• Cell adhesion molecules enable cell-cell contact.
• Ion channels regulate ion passage.
• Transport proteins facilitate molecule movement.
• Ligand receptors bind to specific molecules.
• G proteins mediate signaling cascades.
• Peripheral proteins function as cytoskeletal components.
• Cell signaling proteins transmit signals throughout the cell.

Characteristics of Membrane

• Bilayer arrangement: Phospholipids arrange with their hydrophilic heads facing the exterior and interior environments, and their hydrophobic tails forming the interior of the membrane. Head groups are on the outsides, and fatty acid tails are within the hydrophobic core.
• Asymmetric distribution: Different phospholipids and glycolipids are concentrated on either side of the bilayer.

Fluid Mosaic Model

• The fluid mosaic model describes the membrane as a dynamic structure where components (lipids and proteins) move laterally within the bilayer.

Lipid Rafts

• Lipid rafts are specialized cholesterol-rich microdomains within the membrane.
• They play a role in cholesterol transport, endocytosis, and signal transduction.
• Three types: Glycosphingolipid-enriched membranes (GEMs), polyphosphoinositide-rich rafts, and caveolae.
• Caveolae are flask-shaped invaginations of the cell membrane, containing caveolin, which causes a change in membrane morphology.

Transport Across Membranes

• Membranes import materials for biosynthesis.
• Membranes export waste products.
• Membranes move ions.
• Membranes secrete proteins.
• The barrier function of the lipid bilayer prevents the free transport of large polar molecules and ions.

Different Kinds of Transport

• Passive transport: Thermodynamically favorable, occurs without energy input. Diffusion and facilitated diffusion.
• Diffusion: Movement of small, non-polar molecules across the membrane.
• Facilitated diffusion: Movement of molecules with the help of transport proteins.
• Active transport: Thermodynamically unfavourable, requires energy (ATP).

Types of Transporters

• Channels: Pores (always open). Gated channels (open or close in response to a signal).
• Transporters: Conformational changes. Enzymatic activity.

Glucose Transporter

• Glucose binds to a transporter site on the outside of the cell.
• This binding triggers a conformational change.
• The binding site moves glucose further into the cell.
• The glucose is released to the inside of the cell upon dissociation of glucose from the transporter.
• The transporter reverts to its original form.

Cystic Fibrosis

• Cystic fibrosis is an autosomal recessive disease.
• It is characterized by thick mucus in the lungs and other tissues.
• It involves lung infections, malnutrition, and excessive salt in sweat.
• A mutation in the CFTR gene, coding for a chloride channel, is the direct cause.
• Common causes of CF: deletion, missense, and others.
• Chloride channels are critical in normal lung function and electrolyte transport.
• Mutations in CFTR can cause abnormally thick mucus.
• Inadequate fluid production in the lungs reduces the ability of cilia to remove mucus.

CFTR Channel

• The CFTR protein is a chloride channel.
• It opens in response to phosphorylation.
• CFTR is present in sweat and pancreatic ducts, gut, seminiferous tubules, conducting airways, and other tissues.

Clinical Correlations

• Phospholipids in the cell membrane are found asymmetrically, in particular, in RBCs.

• Macrophages recognize PS and recycle this cell component.

• Normal RBC aging exposes PS as part of the normal aging process.

• Lead poisoning and uremia are examples of conditions affecting RBCs and causing renal failure.

• Respiratory Distress Syndrome (RDS): A major cause of neonatal mortality.

• It's caused by the immaturity of lung development and surfactant deficiency in premature babies.

• The maturity of lung development is assessed by analyzing the ratio of lecithin (lung surfactant) to sphingomyelin in amniotic fluid.

• Ratios below 2.0 indicate an increased risk of RDS.

Test your knowledge on cystic fibrosis, particularly focusing on the ΔF508 mutation and its primary consequences. This quiz will help you understand the genetic basis of this condition and how it affects individuals.