Lipids and Membranes

Transcription

1 Lipids and Membranes Presented by Dr. Mohammad Saadeh The requirements for the Pharmaceutical Biochemistry I Philadelphia University Faculty of pharmacy

2 Biological membranes are composed of lipid bilayers and proteins Biological membrane define the external boundaries of cells and separate compartments within cells. Biological membranes function: 1. Passive barriers to diffusion. 2. some protein in membranes serve as selective pumps that strictly control the transport of ions and small molecules into and out of the cell. 3. generating and maintaining the proton concentration gradients essential for the production of ATP. 4. receptors in membranes recognize extracellular signals and communicate them to the cell interior.

3 Biological membranes are composed of lipid bilayers and proteins A. Lipid bilayers 1. The structure for all biological membranes is the lipid bilayer, which includes amphipathic lipids such as glycerophospholipids, sphingolipids, and sometimes cholesterol. Lipids can diffuse rapidly within a leaflet of the bilayer (figure 9.20). 2. The hydrophobic interaction stabilize the bilayer but allow the structure to be flexible and to be self-seal. 3. A lipid bilayer is typically about 5 to 6 nm thick and consists of two sheets, or monolayers (called leaflets). 4. In each sheets, the polar head groups of amphipathic lipids are in contact with the aqueous medium, and non polar hydrocarbon tails point toward the interior of the bilayer (figure 9.20). Note: Bacteria have double membrane: an outer membrane and an inner plasma membrane.

4 A. Lipid bilayers

5 Biological membranes are composed of lipid bilayers and proteins B. Fluid mosaic of biological membranes is describes features common to all biological membranes (figure 9.21). Biological membrane contains about 25%-50% lipid and 50%-75% protein by mass, with less than 10% carbohydrate as a component of glycolipid and glycoproteins. lipids such as glycerophospholipids, glycosphingolipids, and sometimes cholesterol. Each biological membrane has a characteristic lipid composition (lipid to protein).

6 Figure Fluid mosaic model for membrane structure. The fatty acyl chain in the interior of the membrane from fluid, hydrophobic region, integral proteins float in this sea of lipid, held by hydrophobic interactions with their non polar amino side chains. Both proteins and lipids are free to move laterally in the plane of the bilayer, but movement of either from one face of the bilayer to the other is restricted. The carbohydrate moieties attached to some proteins and lipids of the plasma membrane are exposed on the extracellular face of the membrane.

7 Lipid bilayers and membranes are dynamic structures Both proteins and lipids are free to move laterally in the plane of the bilayer (lateral diffusion), but movement of either from one face of the bilayer to the other is restricted (transversed diffusion, or flip-flop) (figure 9.22).

8 Lipid bilayers and membranes are dynamic structures * Cholesterol account for 20% to 25% of the mass of lipids in mammalian plasma membrane and affected membrane fluidity. * Cholesterol intercalate between hydrocarbon chains of the membrane lipids, the mobility of fatty acyl chains in the membrane is restricted and fluidity decreased at high temperatures (figure 9.26). Cholesterol disrupts the order packing of the extended fatty acyl chains and thereby increases fluidity at low temperature. * Cholesterol in animal cell membranes help maintain fairly constant fluidity despite fluctuations in temperature or degree of fatty acid saturation. * Cholesterol tends to associated with sphingolipids they have long saturated acid. The unsaturated chains of glycerophospholipids produce kinks that don t easily accommodate cholesterol in the membrane.

9 Lipid bilayers and membranes are dynamic structures

10 Three classes of membrane proteins These protein divided into three classes based on their mode of association with the lipid bilayer: 1. Integral membrane proteins. 2. Peripheral membrane proteins 3. Lipid-anchored membrane proteins.

11 Three classes of membrane proteins 1. Integral membrane proteins. Associated firmly with membranes by hydrophobic interaction between the lipid bilayer and their non polar amino acid side chains. Example, bacteriorhodopsin (figure 9.27).

12 Three classes of membrane proteins 1. Integral membrane proteins. Other example, figure 9.28

13 Three classes of membrane proteins 2. Peripheral membrane proteins. are loosely associated with the membrane through electrostatic interactions and hydrogen bond with integral proteins or with the polar head groups of membrane lipids. 3. Lipid-anchored membrane proteins are covalently linked to a lipid anchor in the bilayer.

14 3. Lipid-anchored membrane proteins (figure 9.29)

15 Type of transport through the cell membrane Plasma membranes separate a living cell from its environment. 1. Some small hydrophobic molecules (such as non polar gases O2, CO2, and steroid hormone) can diffuse across the bilayer. 2. Channels, pores, and passive and active transports mediate the movement of ion and polar molecules across channels of membrane. Passive transport, need transport protein, No ATP 3. Active transport required both transport protein and an energy source. 4. Macromolecules can be moved into and out of the cell by endocytosis and exocytosis, respectively (Table 9.3).

16 Membrane transport A. Pore and channels (passive transport) Pore and transport are transmembrane proteins with a central passage for ions and small molecules and don t need energy no energy (figure 9.30).

17 Membrane transport A. Pore and channels: (see video) Example: Potassium channels (Passive transport) allow rapid outward transport of K +. These channels permits K + to pass through the membrane at least times faster than the smaller Na + because Na + is too smaller to interact favorably with the selectivity filter. * Potassium channels Composed of four identical subunits, each subunits has two α-helices with a cone shape. * Carbonyl oxygen of the selective filter remove the water in the hydration sphere of K + (desolvation) and forming a series of coordination shells through which the K + moves (resolvation). Note: Na + retain more water of hydration and therefore transit the filter much more

18 Membrane transport B. Passive transport: is called facilitated diffusion since it dose not require an energy source but need transport proteins. The moves from high concentration to low concentration. The active or passive transport carry out: 1. Uniport, carry only a single type of solute across the membrane. Uniport depend on the external substrate concentration so follow Michaels-Menten equation. 2. Symport, transport of two different solute in the same directions. 3. Antiport, transport of two different solute in opposite directions. See Figure 9.31

19 Membrane transport

20 Membrane transport Models of transport protein operation suggest that a transporter undergoes a conformational change after it binds its substrate. This conformation change allows the substrate to be released on other side of the membrane in both directions; the transporter then reverts to its original state (figure 9.33).

21 Membrane transport C. Active transport: active transport, required energy to move solute against a concentration gradient and/or a charge difference or the membrane potential. *Active transport use a variety of energy sources, ATP, Na + -K + ATPase and Ca + ATPase, create and maintain ion concentration gradients across the plasma membranes of internal organelles. *Primary active transport is powered by a direct energy such as ATP or light.

22 Membrane transport C. Active transport: *Secondary active transport is driven by an ion concentration gradient. The active uphill transport of one solute is coupled to the downhill transport of a second solute that was concentrated by primary active transport example 1 (figure 9.34):

23 Membrane transport B. Active transport: *Secondary active transport example 2: one glucose is imported with each sodium ion that enters the cells. The energy released by the downhill movement of Na + powers the uphill transport of glucose (figure 9.35).

24 The differences between primary and secondary active transport

25