BIOLOGY Lecture Notes - Golden Pages 2003

1. THE CELL

Functions of the Plasma Membrane

The membrane serves not only as a barrier between The Cell and its external environment, but also as a mechanism ensuring the relative constancy of the intracellular composition. In addition, it contains specific receptors for external "signals," the presence of which can mediate diverse responses such as directed cell movement (chemotaxis), stimulation of membrane-bound Enzymes (cyclases), or the generation of chemical (cAMP, cGMP) or electrical signals, as seen in Nerve Cells. The Plasma Membrane is also the site of cell-specific Antigens characteristic of both a given cell type and the mammalian species as a whole. Proteins and specific enzymes localized within the membrane are involved in The transport of ions and metabolites across the membrane barrier. Through invaginations, the plasma membrane can form a continuous network with extensive intracellular channels, facilitating the uptake of substances deep into the cell, and participates in The formation of the space between the inner and outer nuclear membranes.

Class="center">MAIN MECHANISMS OF Membrane Transport

Membrane permeability to various substances depends on both The properties of the solute molecules and the CHARACTERISTICS OF THE membrane. Depending on whether substance Transport Across the membrane requires Energy Expenditure, these processes can be divided into passive transport (movement of substances along a concentration or electrochemical gradient without energy expenditure) and Active Transport (against a concentration and electrochemical gradient with energy expenditure).

Passive transport. The presence of a transmembrane concentration gradient of various molecules acts as the driving force for passive transport. There are two Types of Passive transport: non-mediated transport and mediated transport.

Non-mediated passive Transport of substances is carried out via:

1) simple physical diffusion of molecules. The diffusing molecule is not chemically modified and does not bind to Other types of molecules (e.g., the diffusion of small molecules such as Water, urea, and CO₂);

2) diffusion through the lipid phase, which acts as a solvent for A number of semi-polar substances, including simple and complex esters, higher alcohols, and Fatty acids. In the cell, The rate of free diffusion is enhanced by increasing the transport surface area; for example, the epithelium of the Small Intestine features numerous folds that form microvilli on the membrane surface.

Specific permeability channels exist for certain ions, enabling their rapid, selective passage across the membrane, such as selective channels for K⁺ and Na⁺. Such transport depends on molecular size and ionic charge.

Mediated, or facilitated, membrane transport processes are characterized by saturation kinetics (i.e., the transport system can become saturated with the transported solute) and Specificity for the transported substance. Mediated transport is facilitated by proteins capable of reversibly binding specific substrates. These transport proteins are known as transport systems, transporters, carriers, or translocases. Carriers facilitate the movement of substances down a concentration gradient and do not require metabolic energy expenditure. Examples include The entry of glucose into Liver cells (hepatocytes), erythrocytes, and Muscle cells along a concentration gradient. When a carrier facilitates the movement of one substance in one direction while simultaneously moving another in the opposite direction without energy expenditure, this process is termed exchange diffusion.

Active transport. Active transport refers to processes in which a molecule must move across the membrane regardless of the direction of the concentration gradient. The energy required for this process is supplied in one of two ways. First, the transport of a given metabolite may be coupled with the simultaneous movement of a second substance moving down its concentration gradient. The second molecule may move in the same direction as the first (symport) or in the opposite direction (antiport). Second, energy may be provided by the coupled Hydrolysis of ATP (ATPase activity) or another high-energy compound at The surface of the carrier protein. Such a mechanism is referred to as a pump.

Several major active transport systems have been identified in mammalian Tissues, such as sodium and calcium pumps (Na⁺ pump, Ca²⁺ pump), glucose and other sugar transport systems, and Amino Acid Transport systems. Furthermore, highly selective transport systems involving specific protein carriers can function in transferring specific ions from the extracellular to the intracellular environment.

Active transport processes in which ATP energy is directly utilized to move a substance against a gradient are termed primary active transport. This process differs from transport against a gradient mediated by carriers that utilize the energy of a pre-existing gradient of another substance, most commonly Na⁺ ions. This process is conventionally called secondary active transport.

Na⁺ Pump. In most animal cells, the intracellular [K⁺] concentration is high and stable, ranging from 120–160 mmol/L, whereas the [Na⁺ concentration is < 10 mmol/L. Conversely, extracellular fluid is rich in Na⁺ ions ([Na⁺] ≈ 150 mmol/L) and contains significantly fewer K⁺ ions ([K⁺] < 4 mmol/L). Consequently, a concentration gradient for these two ions is established across the cell membranes. The maintenance of a high intracellular [K⁺] concentration is driven by an energy-consuming efflux of Na⁺ from the cell in exchange for K⁺. The analogy to a mechanical pump is justified in the sense that energy is expended to move ions against an opposing concentration gradient. The energy source for this work is ATP, serving as the substrate for membrane ATPase. For instance, Erythrocyte membranes contain an ATPase that requires both Na⁺ and K⁺ for activation. Na⁺,K⁺-ATPase participates in the transport of Na⁺ and K⁺ across the plasma membrane of all Eukaryotic cells.

Amino Acids and certain sugars are actively transported, which may be accompanied by metabolic alterations of the transported molecules. This coupled exchange transport is mediated by carrier proteins that simultaneously bind the substrate and Na⁺ ions, moving the substance against its concentration gradient driven by the movement of Na⁺ down its gradient. This coupling of Na⁺ and glucose transport suggests the existence of a carrier protein with binding sites for both glucose and Na⁺. Once these sites are discharged inside the cell, the Na⁺ pump returns Na⁺ back to the extracellular environment. Because the latter process requires ATP, the ATP hydrolysis occurring a step earlier once again supplies the energy for glucose transport against its concentration gradient.

Cytosis

Cytosis is a specialized transport mechanism designed for the uptake or release of large molecules by the cell through alterations in membrane shape. Pinocytosis is the process by which a cell engulfs various substrates, wherein the invagination of its membrane culminates in the formation of a pinocytic vesicle surrounding the ingested material. This phenomenon of substrate uptake differs fundamentally from membrane permeability. The ingested material remains outside the cell in the same way that food contained within the intestinal lumen is outside the body. For the internalized substrate to participate in Cellular metabolic processes, it must cross the vesicle membrane. Since the vesicle membrane formed during cytosis is essentially a fragment of the plasma membrane, it can be assumed to retain its properties. Pinocytic vesicles typically have a diameter of 200–700 nm. Most substrates incorporated into the cell via pinocytosis undergo degradation. The fusion of Lysosomes with the contents of pinocytic vesicles results in The breakdown of the material into low-molecular-weight compounds. However, some internalized molecules remain unaltered and can exert pronounced effects on the cell.

Pinocytosis is observed in A wide variety of cells and is particularly well-developed in the epithelial cells of absorptive Organs.

Phagocytosis. During phagocytosis, the cell engulfs an object by extending its membrane around it. This envelopment typically proceeds with the involvement of microfilaments. Once the membrane completely surrounds the phagocytosed particle, its edges fuse. Phagocytosis involves the uptake of substances or solid particles greater than 1 µm in diameter. Phagocytic activity is exhibited by leukocytes (microphages — neutrophils, eosinophils, basophils; macrophages — monocytes, large lymphocytes); Connective Tissue histiocytes; Kupffer Cells of the liver; and alveolar and Lymph node/Spleen macrophages.

Coated vesicles, 60–70 nm in diameter, participate in protein sorting at the plasma membrane. The involvement of these structures in selective (i.e., receptor-mediated) endocytosis was discovered in 1976. Receptors for various ligands on the cell surface cluster into structures known as coated pits. These pits invaginate and pinch off to form coated vesicles, which are then delivered to lysosomes. Most plasma Membrane Proteins are excluded from coated pits. This concentration of certain proteins and exclusion of others results in a 10³–10⁴-fold increase in receptor concentration compared to other membrane proteins. Thus, coated vesicles act as sophisticated sorting machinery.

Clathrin is the major protein component of coated vesicles. Clathrin-coated vesicles are undoubtedly crucial carriers in membrane transport (e.g., the transport of Cholesterol as part of low-density Lipoproteins).

Following endocytosis, receptors are recycled back to the cell surface hundreds of times for reuse, while their bound ligands are efficiently degraded. Receptors manage to evade proteolysis thanks to endosomes—compartments where receptors and ligands dissociate from the complex. The receptors are then returned to the plasma membrane, whereas the ligands are delivered to lysosomes.

Exocytosis is characteristic of all secretory cells, including those producing Hormones, enzymes, Neurotransmitters, and other metabolic products. It represents the exclusive transport mechanism for the release of neurotransmitters (such as acetylcholine and adrenaline) across the presynaptic membrane.