Biochemistry I - The Cell: Biomembrane Structure & Function Lecture PDF

PBC 201 Biochemistry I The Cell : Biomembrane Structure & Function Ahmed Fawzy El-Yazbi, Bharm, PhD, BCPS Faculty of Pharmacy Eukaryotic Cells The basic structure of all eukaryotic cells consists of membranes, organelles and the cytos...

PBC 201 Biochemistry I The Cell : Biomembrane Structure & Function Ahmed Fawzy El-Yazbi, Bharm, PhD, BCPS Faculty of Pharmacy Eukaryotic Cells The basic structure of all eukaryotic cells consists of membranes, organelles and the cytosol The particular design shown in every cell type is determined by its shape and the localization of the organelles Cell shape is determined by the cytoskeleton which is a dense network of three classes of protein filaments The Cytoskeleton permeates the cytosol and provides mechanical support to the cell membranes Different types of proteins attach to the cytoskeleton and depend on it for functioning Biomembranes The lipid composition of the membrane: Affects its shape Determines which proteins get anchored Modify protein activity Transduce different signals to the cytosol Phospholipids in the plasma membrane spontaneously form a bilayer with a hydrophobic core The phospholipid bilayer has two important properties: Its core forms a hydrophobic barrier that prevents the diffusion of water-soluble solutes (membrane proteins modify this property) The core povides membrane stability due to hydrophobic interactions (not disrupted by changes in ionic strength or pH) Membrane Orientation and Adaptation One sheet is cytosolic (facing towards the cytosol) and the other is exoplasmic facing away from the cytosol) (outside vs. inside of the cell?) Cell membrane could be smooth as in case of RBCs to allow flow in blood vessels or protruding into cilia that beat to cause fluid to move as in case of respiratory epithelium Nerve axons have several layers of membrane forming the myelin sheeth Types of Lipids in Biomembranes Three types of amphipathic lipids exist: Phosphoglycerides (PG): phosphatidyl choline is most common, but phosphoesters of ethanolamine, serine, and inositol are present. The polar head interacts strongly with water Sphingolipids (SL): Phospholipids containing sphingosine with choline (sphingomyelins) or sugars (cerebrosides or gangliosides) Steroids: Too hydrophobic to form a bilayer on their own, need to be mixed with phospholipids Lipids move freely in the lateral direction in the membrane Lipid Composition Affects Membrane Properties PGs are synthesized in the endoplasmic reticulum and SLs are synthesized in the Golgi body Membranes rich in sphingomyelin can withstand stress because of its ability to form hydrogen bonds with the free OH (Absorptive side of intestinal epithelium) Shorter and less saturated fatty acid chains do not form strong hydrophobic inteactions and produce kinks in the membrane (increase fluidity) Cholesterol intercalates into the lipid bilayer increasing its thickness and decreasing fluidity (This might help support membrane proteins) Sphingolipids form thicker bilayers The size of the polar head relative to the tail determines the membrane curvature forming pits and microvilli Membrane Microdomains Lipids are not randomly distributed in plasma membrane leaflets Cholesterol and sphingolipids cluster in less fluid areas called lipid rafts that resist extraction with detergents Lipid rafts are disrupted by cholesterol depletion (Antibiotics) Lipid rafts are rich in receptors and signaling proteins This facilitates detection of extracellular signals and responding to them Membrane Protein Components The proteins associated with a particular membrane give it its unique function Some proteins are buried in the lipid bilayer, other are attached to the cytosolic or exoplasmic leaflets Protein domains on the extracellular side of the plasma membrane bind molecules, e.g. hormones, metabolites, signaling molecules, adhesion proteins, in the external environment Protein domains in the bilayer form pores or channels that transport molecules in and out of the cells Domians on the cytosolic side can have several functions such as anchoring cytoskeletal proteins or signaling  Membrane-Protein Interaction Integral membrane proteins (transmembrane proteins): Cross the lipid bilayer Three segments: cytosolic and exoplasmic domains and a transmembrane domain Cytosolic and transmembrane domains have polar amino acids Transmembrane domain has hydrophobic amino acids (helices or sheets) The exoplasmic domain can be bound to sugar residues Lipid anchored membrane proteins: Covalently bound to a membrane lipid component The protein does not enter the bilayer Peripheral membrane proteins: Do not interact with the hydrophobic core Interact with integral membrane protein or polar lipid heads Membrane Glycoproteins Many transmembrane proteins are attached to carbohydrate chains linked to serine, threonine (O-glycosidic link) or asparagine (N- glycosidic link) The carbohydrate chain is oriented towards the extracellular side It can interact with other molecules These glycoproteins form the antigens that determine the blood groups Humans can have different enzymes that make these chains leading to different groups Common Functions of Plasma Membrane Permeability barrier: Transport proteins (channels & pumps) control flow of nutrients and waste products Maintain ionic composition and pH of the cell Membrane proteins and glycolipids form junctions between cells to strengthen tissues and allow cell-cell communication Membrane proteins can anchor extracellular matrix and the cytoskeleton affecting the shape and strength of cells Membrane proteins can act as receptors that interact with signaling molecules Membranes around each cell organelle have their set of proteins that allow the function of this organelle