Mechanisms of vesicular uptake
Pinocytosis (pinocytosis) is the cellular uptake of extracellular fluid with macromolecules dissolved in it. The process begins with the contact of the substance with the cell membrane, after which the membrane invaginates inward to form a vacuole or vesicle. The vesicle pinches off and sinks into the cytoplasm.
The subsequent fate of the captured substrate can follow two scenarios:
- Intracellular metabolism: fusion of the vesicle with a lysosome (lysosoma) and enzymatic degradation of the contents.
- Transcytosis (transcytosis): transit movement of the vesicle across the entire cell to the opposite pole, where the contents are released outward unchanged via exocytosis (exocytosis).
Receptor-mediated endocytosis
Unlike regular pinocytosis, this type of transport is highly specific and proceeds independently of the concentration gradient of substances.
Main stages of the process:
- Binding: the target molecule (ligand) interacts with a specific membrane receptor.
- Coat formation: the intracellular domain of the receptor binds to the protein adaptin, over which a lattice framework of the protein clathrin is assembled. A so-called coated pit is formed.
- Pinching off and "uncoating": the vesicle enters the cytoplasm and sequentially sheds its clathrin coat, followed by the loss of adaptin.
- Sorting: the free vesicle fuses with an early endosome. In the acidic environment of the endosome (at pH 5), the substance molecule detaches from the receptor. Receptors return to the cell membrane for reuse.
- Delivery: the substance is sent to organelles (e.g., the nucleus or Golgi apparatus) or expelled from the cell.
Paracellular transport
Paracellular transport (transportus paracellularis) is the movement of substances in the aqueous phase of intercellular spaces, occurring between cells. This pathway is characteristic primarily of hydrophilic drugs and does not require energy expenditure.
Types of passive movement:
- Passive diffusion: movement of molecules down a concentration gradient (from higher to lower concentration).
- Filtration: movement driven by a pressure difference (osmotic or hydrostatic).
The main limiting factor of this pathway is the size of the transported molecules. Their diameter must not exceed the lumen of the intercellular clefts.
Anatomical barriers for hydrophilic substances
The absorption of hydrophilic drugs directly depends on the histological structure of the tissue at the administration site. For example, intestinal epithelial cells are interconnected by tight junctions (zonulae occludentes). This makes the intercellular spaces very narrow, significantly impeding the penetration of hydrophilic drugs from the intestinal lumen into the systemic circulation.
Similar obstacles to filtration are created by the renal tubular epithelium, the respiratory ciliary epithelium, and the mucous membranes of other parts of the digestive tract. As a result, hydrophilic substances are absorbed and distributed in the body extremely unevenly.
To remember endocytosis proteins: "Adaptin Adapts, Clathrin Constructs Cell (framework)". Adaptin binds the receptor, and clathrin forms the outer protective lattice of the vesicle.
Class and exam questions
How does receptor-mediated endocytosis differ from simple pinocytosis?
It exhibits high specificity for specific macromolecules (e.g., insulin) and occurs independently of the concentration gradient through the formation of the ligand-receptor complex.
Why is the fusion of the transport vesicle with the endosome necessary?
An acidic environment (pH 5) is maintained inside the early endosome. This condition is necessary for the ligand to dissociate from the receptor.
Why are hydrophilic drugs poorly absorbed in the intestine?
They are transported paracellularly, yet intestinal epithelial cells are connected by tight junctions. Large molecules of hydrophilic substances cannot pass through the narrow intercellular clefts.
What else to study on this topic
- Mechanisms of enzymatic degradation of substances inside lysosomes
- The process of membrane receptor recycling following endocytosis
- Features of transcytosis across blood vessel endothelium
- Influence of physicochemical properties of drugs on paracellular diffusion
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