Biochemistry
2nd stageDr.Lamees Majid Al-Janabi
Cell Membrane
Definition:- Membranes are highly viscous plastic structure. Membranes are asymmetric sheet-like enclosed structures with an inside and an outside surface. These sheet-like structures are non-covalent assemblies that are thermodynamically stable and metabolically active.Most of the properties attributed to living organisms( e.g. movement , growth , reproduction, and metabolism) depend, either directly or indirectly, on membranes. All biological membranes have the same general structure. Membranes contain lipid and protein molecules. Because each type of living cell has its own functions, it follows that the structure of its membranes is also unique. The properties of lipid and proteins vary considerably among cell types and among organelles within each cell. The types of lipid and proteins found in each membrane also vary.
In myeline the ratio of protein to lipid 0.23, in mitochondrial inner membrane 3.2, in human erythrocyte 1.1.
** Important Functions:-
Plasma membranes form closed compartments around cellular protoplasm to separate one cell from another and thus permit cellular individuality.The plasma membrane has selective permeability and act as a barrier, thereby maintaining differences in composition between the inside and the outside of the cell. The selective permeability is provided by channels and pumps for ions and substrates and by specific receptors for signal e.g. hormones.
Plasma membranes also exchange material with the extracellular environment by exocytosis and endocytosis , and there are special areas of membrane structures- the gap junction-through which adjacent cells exchange material.
Membranes also form specialized compartments within the cell. Such intracellular membranes form many of the morphologically distinguishable structures (organelles), e.g. mitochondria, endoplasmic reticulum, Golgi complexes, secretary granules, lysosomes and the nuclear membrane.
Membranes localize enzymes, function as integral elements in excitation-response coupling, and provide sites of energy transduction, such as in photosynthesis and oxidative phosphorylation.
** Biomedical importance:-
Gross alterations of membrane structure can affect water balance and ion flux and therefore every process within the cell. Specific deficiencies or alterations of certain membrane components lead to a variety of diseases:-The lysosomal absence of α-glucosidase, causing type II glycogen storage disease.
The lack of an iodide transporter causing congenital goiter.
Defective endocytosis of LDL resulting in accelerated hypercholesterolemia and coronary artery disease.
Composition: -
Lipid.Protein :- non-covalently bound to each other.
Carbohydrate :- Covalently bound to lipid to form glycolipid or to the protein to form glycoprotein. It is responsible for cell recognition and specifity.
**Lipid components: -
There are three classes of lipid present in the cell membrane: -a- Phospholipid. b-Glycosphingolipid. c-Sterols.
Phospholipids: -
Two major phospholipid classes present in membranes: -phosphoglyceride; -
are the more common and consist of a glycerol backbone to which are attached two fatty acids and phosphorylated alcohol. The hydroxyl group is attached to phosphate to form phosphatidic acid. Then in combination with serine, choline, ethanolamine to form lecithins.
Sphingomylines:-
Which contain a sphingosine backbone to which a fatty acid is attached to form ceramide. The in combination with phosphorylcholine to form sphingomyelines which are prominant in myeline sheaths.Glycosphingolipids: -
These are sugar-containing lipids such as cerebrosides and gangliosides. The cerebroside contain a single hexose moiety, glucose or galactose is attached to alcohol group of ceramide, while gangliosides consist of combination of hexose as glucose or galactose and N-acetylamine (N-acetylglucosamine or N-acetylgalactoseamine) and sialic acid (neuraminic acid).Sterols: -
The most common sterol in membranes is cholesterol, which exists almost exclusively in the plasma membranes of mammalian cells but can also be found in lesser quantity in mitochondria, Golgi complexes, and nuclear membranes. Cholesterol is generally more abundant toward the outside of the plasma membrane.
Cholesterol intercalates among the phospholipids of the membrane, with its hydroxyl group at the aqueous interface and the remainder of the molecule within the leaflet.
Above the transition temperature: -
It is rigid sterol ring interacts with the acyl chains of the phospholipids, limits their movement, and thus decrease membrane fluidity.When temperature approaches the transition temperature: -
The interaction of cholesterol with the acyl chains interferes with their alignment with each other, this phenomenon lowers the temperature at which the fuid→gel transition occurs, thus assisting in keeping the membrane fluid at lower temperatures.** Membranes are amphipathic: -
All major lipids in membranes contain both hydrophobicand hydrophilic regions and are therefore termed amphipathic. If hydrophobic, so it is insoluble in water but soluble in oil. If hydrophilic, so it is soluble in water but insoluble in oil.
The amphipathic membrane lipids have a polar head group and non-polar tail. In aqueous environment, the phospholipids and glycolipids are arranged to form: -
1-Micelle: - In which the polar head groups are bathed in water, whereas the hydrophobic hydrocarbon tails are surrounded by other hydrocarbons and thereby protected from water. Micelles are spherical structures.
2- Lipid bilayer or bimolecular layer: -
In which the polar head group on the surface (PL,GL) and the unsaturated fatty acid tails are kinked and lead to more spacing between the polar head groups, hence to more room for movement.Lipid soluble materials can readily enter the cell such as gases O2, CO2, and nitrogen-small molecules with little interaction with solvents-readily diffuse through the hydrophobic region of the membranes.
Lipid derived molecules e.g. steroid hormones, readily transverse the bilayer. Organic non-electrolyte molecules exhibit diffusion rates that are dependent upon their oil water partition coefficient; the greater the lipid solubility of the molecules, the greater is its diffusion rate across the membrane.
While the non lipid soluble molecules across the membrane through the proteins by which the proteins are also amphipathic molecules that can be inserted into lipid bilayer. Proteins form channels for the movement of ions and small molecules and serve as transporters for larger molecules that otherwise could not pass the bilayer.
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**Importance of membrane lipid: -
Membrane fluidity:- the term fluidity describe the resistance of membrane components to movement. Rapid lateral movement is apparently responsible for the proper functioning of many membrane proteins. Membrane fluidity is largely determined by the percentage of unsaturated fatty acids in its phospholipids molecules. A high concentration of unsaturated chains results in membrane that is more fluid.Selective permeability :- Because of their hydrophobic nature, the hydrocarbon chains in lipid bilayers provide a virtually impenetrable barrier to ionic and polar substances. Specific membrane proteins regulate the movement of such substances into and out of cells.
Self-sealing capability:- When lipid bilayers are disrupted, they immediately and spontaneously reseal because a break in a lipid bilayer exposes the hydrophobic hydrocarbon chains to water.
Asymmetry :- Biological membranes are asymmetric, that is , the lipid composition of each half of a bilayer is different e.g.the human red blood cell membrane possesses substantially more phosphatidylcholine and sphingomyelin on its outside surface.
** Protein components:-
Integral proteins :-Most membrane proteins integral components of the membrane(they interact with the phosopholipids and require the use of detergents for their solubilization). These integral proteins are usually globular and are amphipathic. They consist of two hydrophilic ends separated by an intervening hydrophobic region that transverse the hydrophobic core of the bilayer. Integral proteins are asymmetrically distributed across the membrane bilayer.
Peripheral proteins :-
The peripheral proteins do not interact directly with the phospholipids in the bilayer and hence do not require use of detergents for their release. They are weakly bound to the hydrophilic region of specific integral proteins and can be released from them by treatment with salt solutions.** Carbohydrate components:-
It is important in cell recognition, specifity and interaction between cell to cell reaction. They are glycolipid and glycoproteins. The kind of carbohydrates are oligosaccharide consist of (15) molecule which may be sialic acid, L-Fucose, galactose, mannose, N-acylglucosamine.*Asymmetry of membranes:-
This asymmetry is due to:-Irregular distribution of proteins within the membranes.
External location of carbohydrates attached to membrane proteins.
Specific enzymes are located exclusively on the outside or inside of membranes as in mitochondrial and plasma membranes.
There is also inside-outside(transverse) asymmetry of the phospholipids.
The choline-containing phospholipids(phosphatidyl choline and sphingomyelin) are located mainly in the outer molecular layer.
The aminophospholipids(phosphatidylserine and phosphatidylethanolamine) are located in the inner layer.
Cholesterol is generally present in larger amounts on the outside than on the inside.
**Factors affecting the fluidity of the membranes: -
Temperature: - as the temperature increase, the hydrophobic side chains undergo a transition from the ordered state to disordered one, taking a more liquid-like or fluid arrangement.The longer and more saturated fatty acid chains exhibit higher transition temperature i.e. higher temperature are required to increase the fluidity of the structure.
Unsaturated bonds that exist in the cis configuration tend to increase the fluidity of the bilayer by decreasing the compactness of the side chain packing without diminishing hydrophobicity.
Cholesterol acts as a modulator molecule in membranes, producing intermediate state of fluidity.
Significance of fluidity: -
As membrane fluidity increase, so its permeability to water and other small hydrophilic molecules increase.The lateral mobility of integral proteins increases as the fluidity of the membrane increase.
Many of most basic cellular processes including cell movement, cell recognition, cell division, endocytosis not possible if the membrane rigid not fluid.