General Biology (MEMBRAINE PHYSIOLOGY AND ELECTROCHEMICAL GRADIENT)

General Biology

PLASMA MEMBRANE

• Selective transport of molecules into and out of the cell. A function carried out by membrane transport proteins.

• Cell recognition through the use of cell surface antigens. 

• Cell communication through neurotransmitter and hormone receptors and through signal transduction pathways.

• Tissue organization, such as temporary and permanent cell junctions, and interaction with the extracellular matrix, with the use of a variety of cell adhesion molecules.

• Membrane-dependent enzymatic activity

• Determination of cell shape by linkage of the cytoskeleton to the plasma membrane.

CHOLESTEROL AND GLYCOLIPIDS

 It is found in both leaflets and serves to stabilize the membrane at normal body temperature (37°C). As much as 50% of the lipids found in the membrane can be cholesterol.

• Both cholesterol and glycolipids, like the phospholipids, are amphipathic, and they are oriented with their polar groups on the outer surface of the leaflet in which they are located. 

Glycolipids

A minor lipid component of the plasma membrane. These lipids, as their name indicates, consist of two fatty acyl chains linked to polar head groups that consist of carbohydrates.

glycosylphosphatidylinositol (GPI)

• plays an important role in anchoring proteins to the outer leaflet of the membrane. 

LIPID BILAYER

•  not a static structure. The lipids and associated proteins can diffuse within the plane of the membrane. 

• The fluidity of the membrane is determined by temperature and by its lipid composition. As temperature increases, the fluidity of the membrane increases. 

• The presence of unsaturated fatty acyl chains in the phospholipids and glycolipids also increases membrane fluidity. If a fatty acyl chain is unsaturated, the presence of a double bond introduces a “kink” in the molecule.

• Although the lipid bilayer is “fluid,” movement of proteins in the membrane can be constrained or limited. 

kink

•  prevents the molecule from associating closely with surrounding lipids, and, as a result, membrane fluidity is increased. 

MEMBRANE PROTEINS

• As much as 50% of the plasma membrane is composed of proteins. 

• These membrane proteins are classified as integral, lipid-anchored, or peripheral.

INTEGRAL MEMBRANE PROTEINS

imbedded in the lipid bilayer, where hydrophobic amino acid residues are associated with the hydrophobic fatty acyl chains of the membrane lipids. 

• Hydrophilic amino acid residues are then exposed to the aqueous environment on either side of the membrane. 

• Transmembrane proteins may pass through the membrane multiple times.

transmembrane proteins.

Many integral membrane proteins span the bilayer; such proteins. have both hydrophobic and hydrophilic regions. The hydrophobic region, often in the form of an α helix, spans the membrane. 

LIPID ANCHORED PROTEINS

• A protein can also be attached to the membrane via lipid anchors. 

• The protein is covalently attached to a lipid molecule, which is then embedded in one leaflet of the bilayer. 

• Glycosylphosphatidylinositol (GPI) anchors proteins to the outer leaflet of the membrane. 

• Proteins can be attached to the inner leaflet via their amino-terminus by fatty acids (e.g., myristate or palmitate) or via their carboxyl-terminus by prenyl anchors (e.g., farnesyl or geranylgeranyl).

PERIPHERAL PROTEINS

may be associated with the polar head groups of the membrane lipids, but they more commonly bind to integral or lipid-anchored proteins

GLYCOCALYX

• some of the outer leaflet lipids, as well as many of the proteins exposed on the outer surface of the membrane, are glycosylated (i.e., have short chains of sugars, called oligosaccharides, attached to them).

• Composed of  glycolipids and glycoproteins.

• Depending on the cell these glycolipids and glycoproteins may be involved in cell recognition (e.g., cell surface antigens) and formation of cell-cell interactions (e.g., attachment of neutrophils to vascular endothelial cells).

MEMBRANE TRANSPORT

• approximately 10% of human genes (≈2000) code for transporters. They are also targets for numerous drugs. 

• The intracellular and extracellular fluids are composed primarily of H2O, in which solutes (e.g., ions, glucose, amino acids) are dissolved.

• It also restricts the movement of water across the membrane. 

• The presence of specific membrane transporters in the membrane is responsible for the movement of these solutes and water across the membrane.

MEMBRANE TRANSPORT PROTEINS

WATER CHANNELS

ION CHANNELS

CHANNEL CONDUCTANCE

SOLUTE CARRIERS

WATER CHANNELS

• Water channels, or aquaporins (AQPs), are the main routes for water movement into and out of the cell. 

• They are widely distributed throughout the body (e.g., the brain, lungs, kidneys, salivary glands, gastrointestinal tract, and liver). 

• Cells in the collecting ducts of the kidneys express AQP3 and AQP4 in their basolateral membrane and AQP2 in their apical membrane. 

• Moreover, the abundance of AQP2 in the apical membrane is regulated by antidiuretic hormone (also called arginine vasopressin), which is crucial for the ability of the kidneys to concentrate the urine.

• Although all AQP isoforms allow the passive movement of H2O across the membrane, some isoforms also provide a pathway for other molecules such as glycerol, urea, mannitol, purines, pyrimidines, CO2, and NH3 to cross the membrane. 

• Because glycerol was one of the first molecules identified as crossing the membrane via some AQPs, this group of AQPs is collectively called aquaglyceroporins 

ION CHANNELS

- are found in all cells, and are especially important for the function of excitable cells (e.g., neurons and muscle cells). 

- are classified by their selectivity, conductance and mechanism of channel gating (i.e., opening and closing). 

Selectivity

defined as the nature of the ions that pass through the channel. 

CHANNEL CONDUCTANCE 

The conductance varies, depending on the direction in which the ion is moving. 

For example, if the channel has a larger conductance when ions are moving into the cell than when they are moving out of the cell, the channel is said to be an inward rectifier. 

Gating

ion channels fluctuate between an open state or a closed state

SOLUTE CARRIERS

- Solute carriers (denoted SLCs by the HUGO Gene Nomenclature Committee) represent a large group of membrane transporters categorized into more than 50 families; almost 400 specific transporters have been identified to date.