Membrane transport mechanisms can be classified as:
* Passive diffusion: along an electrochemical gradient. Diffusion refers to the random movement of particles in solution from an area of higher concentration to one of lower. This may involve either dissolution and diffusion in membrane lipid, or passage through ion channels. Ion channels may be permanently open (non-gated, passive, or leakage) or be gated, i.e. can be opened or closed: e.g., voltage-gated; extracellular or intracellular ligand-gated; mechanically gated (mechanical deformation); ion-gated; or gap junction activation. Voltage-gated channels are found in neurons and muscle cells. Mechanical gating is exemplified by the mechanical deformation of cilia of the hair cells of the inner ear brought about by sound waves.
* Facilitated transport: aided by membrane transporters (carrier proteins) in the direction of the electrochemical gradient. The process is more rapid than simple diffusion. Carriers must be able to recognise the substance transported, to permit translocation, followed by release of the substance with recovery of the carrier.
* Active transport: an energy requiring process operating against an electrochemical gradient. The process can be mediated by:
Primary ATPases: Na+/K+-ATPase; H+-ATPase; K+/H+-ATPase; Ca2 +-
ATPase: these transporters are known as pumps. Adenosine 5'-triphosphate (ATP)-binding cassette proteins, which bind ATP and use the free energy from ATP hydrolysis to selectively transport materials, e.g. the cystic fibrosis transmembrane conductance regulator. These
Steps in receptor-mediated endocytosis
Specific binding of ligand to high-affinity receptor, which is clustered in pits coated 3
with clathrin. a
Internalisation of the receptor in its coated pit, forming a coated vesicle. e
Coated vesicles lose their clathrin coats after endocytosis, and fuse with other vesicles a to form early endosomes. p o
The receptors are recycled to the surface in vesicles that fuse with the cell membrane. t
The process is used in cellular uptake of cholesterol (via the low density lipoprotein (LDL) receptor) and of iron, among other substances.
proteins comprise a ligand-binding domain at one surface and an ATP-binding domain at the other. Secondary mechanisms, being coupled to Na+ or H+ transport. The mechanism can be either a co-transport (symport) or a counter-transport (antiport system): K+/H+-ATPase or proton pump.
• Osmosis: the passage of water from a region where its concentration is high, through a semi-permeable membrane, into a region where its concentration is lower.
• Vesicular transport, which can be classified as:
Pinocytosis: the plasma membrane forms vesicles that trap extracellular fluid; Phagocytosis;
Exocytosis: fusion of membrane-bound vesicles with the plasma membrane, allowing their contents to be released into the extracellular space.
This depends on: The concentration gradient of the solute across the membrane; The permeability of the membrane to the solute; The transmembrane voltage gradient; The molecular weight of the solute; The membrane surface area; The distance over which diffusion occurs.
The rate of diffusion is proportional to the cross-sectional area and to the change in concentration per unit distance, i.e. the concentration gradient across the membrane (Fick's law). Fick's law may be stated as:
0 Where Q = the rate of flow of solute at right angles to the interface between two
g dc/dx = the concentration gradient (mg/ml) across the interface
A = the area of the interface (cm) D = the diffusion coefficient (sq cm/s)
The permeability constant P = D/d, where D is the diffusion coefficient and d is the width of the membrane
Facilitated transport demonstrates the following characteristics: Specificity for the transported solute; Movement along an electrochemical gradient;
Saturation kinetics: saturation at high substrate concentrations owing to the limited number of binding sites on the carrier; Inhibition by structurally similar substrates; No energy expenditure.
Active transport demonstrates the following characteristics: Specificity for the transported solute. Movement against an electrochemical gradient. Saturation kinetics: saturation at high substrate concentrations. Metabolic energy requirement. Energy dependence leads to active transport being substrate and oxygen dependent. Inhibition by metabolic poisons such as cyanide and dinitrophenol may occur. Profound inhibition may result from lowering of ambient temperature. Competition for uptake by similar substrates.
Kinetic characteristics shared by facilitated diffusion and active transport processes
* Stereochemical specificity. Thus amino acid transport systems of cell membranes are much more active with L-amino acids than the D isomers.
* Saturation, i.e. the transport system can become saturated with the substance being transported. Plots of the rate of transport against substrate concentration usually show a hyperbolic curve approaching a maximum at which the rate is zero order with respect to substrate concentration.
* Competitive inhibition by other transported species (structurally related 5
compounds). m e
* Non-competitive inhibition by carrier poisons, which can block or alter 3 specific functional groups of proteins. n
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