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CMU BSC 03231 - lecture

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Biochemistry I Lecture 23 Oct 26, 20051Lecture 23: Biological MembranesAssigned reading in Campbell:Chapter 8.3-8.6Key Terms:• Phospholipids (PC, PS, PE, PI and PA)• Peripheral & Integralmembrane Proteins• Membrane Fluidity• Functions of Biological Membranes1. PhospholipidsA. Structure & Nomenclature• Two fatty acids + glycerol + phosphate + a head group form a phospholipid.• Various head groups are attached to the phosphate, giving a diverse set of lipidsKnow the structure of either PC or PS as an example.2. Membrane ProteinsPeripheral Membrane Proteins:• Loosely attached to membranes viaelectrostatic interactions – releasedwith high salt.Integral Membrane Proteins:• Largely contained within the membrane(solubilization requires disruption of themembrane by detergents).• Often span the entire membrane.• Stability energetics are similar to watersoluble proteins, except that non-polar groups interact with acyl chains in the membrane. The rule here is: "hydrophobic outside - hydrophilic or hydrophobic inside", thereby matching the location.• Asymmetry across the bilayer is required for most functions (both lipid and protein). No flip-flop!Head group(-X)Name ofPhospholipidNet Chargenonephosphatidic acid(PA)-1choline(-C-C-N+(CH3)3)Phosphatidylcholine(PC)0(zwitterion)Serine (linkage viasidechain)Phosphatidylserine(PS)-1ethanolamine(-C-C-NH3+)Phosphatidyl-ethanolamine (PE)0(zwitterion)inositol(C6H6O5)Phosphatidylinositol(PI)-1Fatty AcidsPhospholipidsTriglyceridesBiological MembranesCholesterolProteins(Energystorage)(Permeability Barrier)Biochemistry I Lecture 23 Oct 26, 20052• Transport (e.g. of protons, metabolites, electrons)v Passive transport (no energy required, molecules go from high concentration to low)v Active transport (energy required, molecules are pushed from low to high concentration) 3. Cholesterol enhances membrane fluidity:Lipid bilayers undergo a highly cooperative phase transition with a defined Tm:• Below Tm the the acyl chains are tightly packed and the lipids exist as a solid-like gel; .• Above Tm the acyl chains are disordered and the lipids are in a liquid-like liquid crystal phase.• Rapid lateral diffusion of lipids and proteins occurs in the plane of the membranes above butnot below Tm.v Membrane fluidity is essential for the biological function of membranes. Therefore organisms go togreat lengths to maintain a fluid membrane bilayer (eg, bacteria regulate acyl chain length).v Lipid bilayers can be made more fluid (higher Tm) either by decreasing fatty acyl chain length and/orincreasing the degree of unsaturation. (Chain length and the presence of cis-double bonds cangreatly affect Tm and fluidity through affecting the extent of van der Waals packing)DMPC (C14) = 23 C DPPC (C16) = 41 CDSPC (C18) = 58 CDOPC (C18:1) = -22Biochemistry I Lecture 23 Oct 26, 20053v But simply increasing the degree of unsaturation can compromise the integrity of the cell membrane.Animals cells have another way of increasing membrane fluidity:Cholesterol:- Is a natural steroid, you produce about 1 g/day!- About the same length as a C16 fatty acid; therefore it reaches across half of the bilayer. - Essential component of most mammalian membranes (~20% of cell membrane lipid) - Destroys the phase transition of pure lipid membranes, thereby keeping the membranes fluid below the phase transition and more rigid above the phase transition. Often referred to as a membrane plasticizer. Fluid mosaic model of Biological Membranes• Lipids, membrane proteins, glycolipids, etc… float in a 2-D fluid membrane.• Rapid lateral diffusion of components (~1 µm/sec!).• Different types of lipids – composition varies (type & acyl chain) by organism, tissue type, andtemperature.• The membrane completely encloses the cell (or intracellular organelle) and therefore definescellular topology (i.e. an inside and an outside).* Transport of molecules and ions occurs across membranes.* Generation of a concentration difference across the membrane can be used to produce energy.* Signal transduction occurs across the


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