Medical Physiology

Functional organization of the cell

Structure of biological membranes

1. The surface of the cell is defined by a membrane.

Cell contains its unique environment by membrane. The large molecules cannot pass through the membrane. Small molecules and water yes by selectively permeable. It uses energy to active transport things to maintain its environment.

2. The cell membrane is composed primarily of phospholipids

Phosphatidylethanolamines, phosphatidylionsitols, phosphatidylserines, phosphatidylcholines.

Shingolipids: sphingomyelins, glycosphingolipids, gangliosides

Cholesterol

Mixed lipids changes the fluidity and transition temp of membrane

Especially the cholesterol molecules, at high concentration increases fluidity

At low concentration lower the fluidity of membrane

3. Phospholipids form complex structures in aqueous solution

At high concentration phospholipids spontaneously form bilayers

4. Diffusion of lipids within a bilayer is determined by chemical makeup of its constituents

Higher temp sol state

Lower temp gel state

Temp to make change from gel to sol state is transition temp

Longer the fatty tail the higher the transit temp

Transition temp is a range. During this range the membrane may divided into compositionally distinct zones.

5. Phospholipid bilayer membrane areimpermeable to charged molecules

Impermeable: Na+, K+, Ca++, proteins, nucleicacids, sugars and nucleotides

Permeable: O2, CO2, NH3, H2O. water permeability depends on composition of membrane.

6. The plasma membrane is a bilayer

7. Membrane proteins can be integrally or peripherally associated with the plasma membrane

8. Peripheral proteins are neither embedded within nor attached to membrane by covalent bonds. Instead they adhere tightly to the cytoplasmic or extracellular surfaces of the plasma membrane. They can be removed from the membrane by mild treatments that disrupt ionic bonds (very high salt concentrations) or hydrogen bonds (very low salt concentrations)

Integral membrane proteins are intimately associated with the lipid bilayer in three ways:

Transmembrane proteins: span in membrane once or several times

Partial embedded proteins.

Covalent bonded protein.

Intercalates to glycosylphosphatidylinositol(GPI), -outer leaflet.

Direct linkage to a fatty acid or a prenyl group that intercalates into inner leaflet.

9. The membrane spanning portions of transmembrane proteins are usually hydrophobic @ helices(~3.6 amino acids / turn)

There are eight amino acids are hydrophobic.

Many membrane proteins form tight nonconvalent associations with other membrane proteins in the plane of the bilayer. Multimeric proteins complexes increase stability and functions.

10. Some membrane proteins are mobile in the plane of the bilayer

Function of membrane proteins

1. Integral membrane proteins can serve as receptors

Ligand binding receptors: conformational change in membrane proteins extended through the membrane

2. Integral membrane proteins can serve as adhesion molecules.

To extracellular matrix or neighbor cells. Good in regulatin the shape, growth and differentiation of cells.

Integrins: matrix receptos - cell matrix adhesion molecules.

Cell cell adhesion molecules attach cells to each other. It includes Ca++ dependent cell adhesion molecules ( cadherins) and Ca++- independent neural cell adhesion molecules ( N-CAMs). The cadherins are glycoproteins(protein with sugars attached) with one membrane spanning segment and a large extracellular domain that binds Ca++. The N-CAMs, generally are members of the immunoglobulin superfamily. The two classes of cell-cell adhesion molecules mediate similar sorts of transmembrane signals that help organize the cytoplasm & control gene expression in response to intercellular contacts. Some of them belong to the GPI-linked class of membrane proteins. These polypeptides lack a transmembrane & cytoplasmic tail. How to communicate?

Loss of this type adhesion is a hallmark of tumor cells.

3. Integral mem proteions can carry out the transmembrane movement of water-soluble substances.

Ions and other mem impermeable substances can cross the bilayer with the assistance of transmembrane proteins that serve as pores, channels, carries & pumps.

Pores & channels serve as conduits that allow water, specific ions or even very large proteins to flow passively through the bilayer.

Carriers can either facilitate the transport of a specific molecule across the mem or couple the transport of a molecules to that of other solutes.

Pumps use the energy that is released by ATP to drive the transport of substances into or out of cells against energy of concentration gradients.

Channels, carriers and pumps transport items by creating a hydrophilic pathway in the bilayer. @-helices are amphipatic.

4. Integral mem proteins can also be enzymes.

Many of GPI linked proteins are enzymes. Alkaline phosphatase and 5 nucleotidase. Extracellular. Phospholipase C can cleave of them.

5. Integral mem proteins can participate in intracellular signaling

These proteins bind to fatty acids or prenyl group into intracellular side to participate in intracellular signaling & growth regulation pathwas. GTP guanosine triphosphate binding proteins, kinases and oncogene products.

6. Peripheral me proteins participate in intracellular signaling and can form a submembranous cytoskeleton.

Cellular organelles and the cytoskeleton

1. The cell is composed of discrete organelles

The nucleus stores, replicates and reads the cells genetic info.

Lysosomes digest material that is derived from the interior and exterior of cells. Inside of lysosomes contain digestion enzymes and high acidic liquid.

Mitochondrion is the site of oxidative energy production.

The cytoplasm is not amorphous but is organized by the cytoskeleton

The cytoskeleton is composed of protein filaments that radiate throughout cell, serving as beams, struts and stays that determine cell shape and resilence.

Intermediate filaments provide cells with structural support

Microtubules provide structural support & provide the basis for several types of subcellular motility.

2. Synthesis and recycling of membrane proteins

Secretory and mem proteins are synthesized in association with the rough endoplasmic reticulum.