Oct 2009

LSM 1101 Biochemistry of Biomolecules Dr. Swamis class notes Class 2a, 2b: Lipids 1a, 1b In lipids, we study three sections: membrane, lipid molecules and lipid metabolism. Membrane: The study on membrane is very important as the material of choice for the outer cover of all the cells of all organisms, except plants, are made my membrane. In plant cells, as an additional layer of protection, the membrane is surrounded by the cell wall. The major component of membrane is lipid molecules. The membrane is made by two layers of lipid molecules and also is known as lipid bilayer. The lipid molecules of membrane have smooth hydrophilic heads and long chains in the hydrophobic tail portion. Using the freeze etching technique, membrane is frozen and the two layers can be separated and the embedded components can be studied in detail. Membrane contains several molecules, including proteins. Physical properties of membrane: When lipid molecules are thrown into water, the hydrophilic heads orient to contact water and the hydrophobic tails orient in the opposite side to be in contact with air. A single tailed lipid molecule contains a tapered van der Waals envelope. An optimum number of these lipid molecules form a sphere, called micelle. If more lipid molecules are pushed into the micelle, a gap is introduced, which will allow water to leak into the hydrophobic core thereby de-stabilizing the micelle. The system will try to push out the water and the extra lipid molecules to return back to the stable conformation. Similarly, if you flatten a micelle, the same effect happens. A double tailed lipid molecule has a cylindrical van der Waals envelope. A collection of these double tailed lipid molecules also will form a micelle. The central region of the micelle will form a lipid bilayer. An extended flat arrangement of such double tailed lipid molecules represents membrane. In the bilayer of membrane, lipid molecules travel easily from one place to another place in the same layer, called lateral diffusion. However, it is very difficult for a lipid molecule to travel from one layer to another layer (called transverse diffusion). In a way, you can imagine membrane is like a swimming pool, filled with floating rubber balls. You can push away the balls and walk across the swimming pool. A ball can easily be pushed from one point to another point on the surface of the pool. However, it is really uneasy and impractical to push a ball from the top of the swimming pool to the bottom. The lipid molecules become rigid below a particular temperature, called the transition temperature, which is specific for each type of lipid molecule. Apart from double tailed fatty acids, membrane contains other types of lipid molecules. The membranes of different organisms contain different composition. Even within the same organism, the composition of each cell membrane is different.

Functions of membrane: Membrane does the following functions. Physically, they arrange the organelles of a cell in invaluable compartments (Delineation and compartmentalization). Each organelle has its own function, grouped my membrane (Organization and localization of functions). Membrane is used to regulate what goes into and what comes out of a cell (Transport). Membrane proteins act as antenna to receive ligands to communicate with the surrounding and initiate a biochemical reaction inside the cell (Signal detection). Also, two cells in a tissue bind and align to each other through membrane proteins and interact with each other (Cell-to-cell communication). Fluid mosaic model of membrane: Membrane is not like plastic sheet. The lipid molecules make membrane flexible (fluid). Also, it is not just the membrane molecules and there are embedded proteins in membrane. The embedded proteins form a pattern (mosaic). The validity of this model was demonstrated by the cell fusion experiment. A mouse cell was first treated with antibodies that were specific for the membrane proteins of the cell. To the antibodies, a fluorescent dye, say red, was attached. Similarly, a human cell was prepared but with a green dye. These two cells were made to fuse using the membrane encapsulated Sendai virus. Even though initially the two colors were observed only on the respective cell region, after some time, the dyes diffused throughout the fused cell, demonstrating that the attached protein molecules could freely move in the membrane. Membrane proteins: Proteins attached to membrane are categorized as integral or intrinsic (completely embedded) proteins and peripheral or extrinsic (partially embedded) proteins. An integral protein has hydrophilic regions that extend outward to the aqueous environment and buried hydrophobic regions. Some proteins, known as transmembrane proteins, span the membrane. The number of segments and orientation vary according to function. Integral proteins not easily removed. It can be with -helices or -strands. The hydropathy plot of a protein identifies the hydrophobic and hydrophilic regions of the protein. Each amino acid has a hydropathy index. The cumulative sum of hydropathy indices for say, 10 amino acids (amino acids 1 to 10) is plotted against position 1, for amino acids 2 to 11 against position 2 and so on. The reason to take a window of 10 amino acids is to accept the fact that we want to know a hydrophobic or hydrophilic regions in a protein and not how each amino acid in a region behaves. This means, there can be one or two hydrophilic amino acids among predominantly hydrophobic amino acids that form a hydrophobic region and vice versa. Peripheral (or extrinsic) proteins have no discrete hydrophobic sequences. They do not penetrate deep into the lipid bilayer. They interact with membrane weakly and can be easily removed. The erythrocyte (red blood cell) is one of the well studied membrane systems. It possesses no organelles and is involved with minimum function. Its biconcave shape facilitates O2 diffusion to hemoglobin and its membrane contains several proteins. The blood groups (A, B, AB, O) are marked by the presence of A, B antigens (components of erythrocyte surface sphingoglycolipids), both antigens or no antigen, respectively.