Q2 LONG ANSWER 10M ★ High-yield

Describe the structure of the plasma membrane. Explain the mechanisms of transport across it.

Biochemistry · 1st Professional — Pre-Clinical

Composition

The plasma membrane is a selectively permeable boundary composed of lipid (about 50%), protein (about 45%) and carbohydrate (about 5%).

Component	Types	Role
Phospholipids	Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin	Form the bilayer; amphipathic
Cholesterol	—	Modulates fluidity — prevents both excessive rigidity and excessive fluidity
Glycolipids	Cerebrosides, gangliosides	Cell recognition; blood group antigens; always on the outer leaflet
Integral proteins	Transmembrane	Transporters, channels, receptors, enzymes; removed only by detergents
Peripheral proteins	Surface-attached	Structural and signalling; removed by changes in salt or pH

Fluid Mosaic Model

Proposed by Singer and Nicolson (1972)
A lipid bilayer behaving as a two-dimensional fluid, in which proteins float like icebergs in a sea
Lateral diffusion is rapid; transverse movement (flip-flop) is very slow and needs flippase enzymes
Asymmetric — phosphatidylcholine and sphingomyelin predominate on the outer leaflet, phosphatidylserine and phosphatidylethanolamine on the inner; all carbohydrate faces outward

CLINICAL PEARL

The asymmetry is functional, not incidental. When phosphatidylserine appears on the outer surface it signals apoptosis, marking the cell for phagocytosis, and it also provides the surface on which the coagulation cascade assembles.

Factors Affecting Membrane Fluidity

Increases fluidity	Decreases fluidity
Unsaturated fatty acids (cis double bonds kink the chain)	Saturated fatty acids
Shorter chain length	Longer chains
Higher temperature	Lower temperature
Cholesterol below the transition temperature	Cholesterol above the transition temperature

Cholesterol acts in both directions — it is a fluidity buffer, keeping the membrane within a workable range

Transport Across the Membrane

Mechanism	Carrier	Energy	Gradient	Examples
Simple diffusion	None	None	Down	O2, CO2, steroids, water, urea
Facilitated diffusion	Yes	None	Down	GLUT transporters, aquaporins, anion exchanger
Primary active transport	Yes	ATP directly	Against	Na+/K+-ATPase, Ca2+-ATPase, H+/K+-ATPase
Secondary active transport	Yes	Ion gradient	Against	SGLT-1 and SGLT-2, Na+–amino acid cotransport
Ion channels	Channel protein	None	Down	Voltage- and ligand-gated Na+, K+, Ca2+ channels
Endocytosis / exocytosis	Vesicles	ATP	—	LDL receptor uptake, phagocytosis, insulin release

Distinguishing simple from facilitated diffusion

Facilitated diffusion is saturable, shows substrate specificity, can be competitively inhibited, and follows Michaelis–Menten kinetics
Simple diffusion is linear with concentration and never saturates

The Sodium–potassium Pump

3 Na+ out, 2 K+ IN per ATP hydrolysed → Creates the Na+ and K+ gradients → Generates the resting membrane potential (electrogenic) → The Na+ gradient powers secondary active transport → Maintains cell volume by countering the Donnan effect

It consumes 20–30% of resting ATP, and far more in kidney and brain
Inhibited by digoxin and ouabain — the rise in intracellular sodium reduces Na+/Ca2+ exchange, so calcium accumulates and cardiac contractility increases

Other Membrane Functions

Selective permeability and maintenance of the internal environment
Signal transduction — receptors for hormones and neurotransmitters
Cell recognition and adhesion — glycocalyx, blood group antigens, MHC molecules
Electrical excitability in nerve and muscle
Site of many enzymes — adenylate cyclase, alkaline phosphatase

Endocytosis and Exocytosis

Process	Description	Example
Phagocytosis	"Cell eating" — large particles	Neutrophils and macrophages engulfing bacteria
Pinocytosis	"Cell drinking" — fluid and solutes	Non-specific uptake
Receptor-mediated endocytosis	Specific; via clathrin-coated pits	LDL uptake, transferrin, insulin
Exocytosis	Vesicle fuses with the membrane and discharges	Insulin secretion, neurotransmitter release

Receptor-mediated endocytosis is defective in familial hypercholesterolaemia — the LDL receptor cannot bind or internalise its ligand

Applied Aspects

Cystic fibrosis — a defective CFTR chloride channel → viscid secretions; the sweat chloride test is diagnostic
Cholera toxin locks adenylate cyclase on → massive chloride and water secretion. ORS works because SGLT-1 remains intact and glucose drags sodium and water with it
Hereditary spherocytosis — defective spectrin and ankyrin of the membrane skeleton → loss of the biconcave shape and splenic destruction
Liposomes, built from the same bilayer principle, are used to deliver amphotericin B and doxorubicin with less toxicity
Local anaesthetics and general anaesthetics act on membrane channels and lipids
Membrane fluidity falls with cholesterol loading, which stiffens the red cell in liver disease and produces target cells

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