Biochemistry chapter 11

Membranes

Chapter Overview

  • Covers the function and structure of biological membranes

  • Dynamics and functionality of membrane proteins

  • Mechanisms of transport across biological membranes

Structure and Composition of Membranes

  • Lipids aggregate into structures in water

    • Structural formation depends on:

    • Type of lipid

    • Concentration

  • Types of lipid structures:

    • Micelles

    • Liposomes (Vesicles)

    • Bilayers

Micelles

  • Formed in solutions of amphipathic molecules with larger heads than tails.

  • Examples:

    • Fatty acids

    • Sodium dodecyl sulfate

  • Characteristics:

    • Each micelle contains from dozens to thousands of lipid molecules.

    • Aggregation occurs when the concentration exceeds a certain threshold.

Vesicles (Liposomes)

  • Small bilayers spontaneously seal into spherical shapes.

  • Can contain artificially inserted proteins.

  • Central aqueous cavity can enclose dissolved molecules.

  • Applications:

    • Serve as artificial carriers (e.g., drug delivery).

    • Fuse readily with cell membranes or each other.

Membrane Bilayer

  • Composed of two leaflets of lipid monolayers:

    • Hydrophilic head groups interact with water.

    • Hydrophobic fatty acid tails are inner-packed.

  • Orientation:

    • One leaflet faces the cytoplasm.

    • The other faces the extracellular space or the membrane-enclosed organelle.

Definition of Membranes

  • Complex lipid-based structures forming pliable sheets.

  • Composed of varied lipids and proteins; some lipids/proteins are glycosylated.

  • All cells possess a cell membrane, separating them from their surroundings.

  • Eukaryotic cells have internal membranes compartmentalizing their internal space.

Functions of Membranes

  • Define cell boundaries.

  • Allow for import and export:

    • Selective import of nutrients (e.g., lactose).

    • Selective export of waste and toxins (e.g., antibiotics).

  • Retain metabolites and ions within the cell.

  • Sense external signals, transmitting information into the cell.

  • Provide compartmentalization within cells:

    • Separate energy-producing from energy-consuming processes.

    • Keep proteolytic enzymes isolated from crucial cellular proteins.

  • Produce and transmit nerve signals.

  • Store energy via proton gradients.

  • Support ATP synthesis.

Common Features of Membranes

  • Sheet-like, flexible structure measuring 30–100 Å (3–10 nm) thick.

  • Main structure: two bilayer leaflets.

    • Hydrophobic interactions stabilize the bilayer structure.

  • Membrane proteins may span the lipid bilayer.

  • Membrane asymmetry:

    • Lipids and carbohydrates show preferential distribution inside and outside the cell.

  • Electrically polarized with an interior negative charge (~-60mV).

  • Fluid structures, allowing lateral mobility of components inside the bilayer.

Fluid Mosaic Model of Membranes

  • Proposed by Singer and Nicholson in 1972.

  • Concept:

    • Lipids create a viscous two-dimensional solvent where proteins are embedded.

  • Protein Types:

    • Integral Proteins: Firmly associated with the membrane, often spanning the bilayer.

    • Peripheral Proteins: Weakly associated, easily removable (noncovalently linked or linked to membrane lipids).

Composition of Membranes

Variability in Composition

  • Variation in lipid composition across organisms, tissues, and organelles:

    • Different ratios of lipids to proteins.

    • Variation in types of phospholipids and sterols.

    • Prokaryotes typically lack sterols; cholesterol is predominant in plasma membranes but absent in mitochondria.

    • Plant chloroplasts have abundant galactolipids, which are nearly absent in animals.

Membrane Composition by Organism (Table 11-1)

  • Human myelin sheath:

    • Protein: 30%

    • Phospholipid: 30%

    • Sterol (Cholesterol): 19%

    • Other lipids (Galactolipids, plasmalogens).

  • Mouse liver:

    • Protein: 45%

    • Phospholipid: 27%

    • Sterol (Cholesterol): 25%

  • Maize leaf:

    • Protein: 47%

    • Phospholipid: 26%

    • Sterol (Sitosterol): 7%

  • Yeast:

    • Protein: 52%

    • Phospholipid: 7%

    • Sterol (Ergosterol): 4%

  • E. coli:

    • Protein: 75%

    • Phospholipid: 25%

Archaeal Membrane Structure

  • Unique phospholipid structure:

    • L-glycerol in archaea vs D-glycerol in bacteria.

    • Ether linkages in archaea compared to ester linkages in bacteria.

  • Membrane topology can be either monolayer in some archaea or bilayer in all bacteria.

Lipid Monolayers in Archaea

  • Examples include Sulfolobus solfataricus found in volcanic hot springs at temperatures 75–80°C and acidic pH of 2–3.

  • These membranes exhibit enhanced stability through isoprenoid tetraethers with unique alcohols.

Membrane Asymmetry

  • Composition Differences:

    • The two leaflets exhibit different lipid compositions: the outer leaflet is often positively charged.

  • Phosphatidylserine:

    • When found outside, activates blood clotting in platelets; serves as a marker for destruction in other cells.

Membrane Proteins

Functions

  • Receptors: Detect signals from the external environment such as light (opsin), hormones (insulin receptor), and neurotransmitters (acetylcholine receptor).

  • Channels/Gates/Pumps: Facilitate transport of nutrients (maltoporin), ions (K-channels), and neurotransmitters (serotonin reuptake protein).

  • Enzymes: Participate in lipid biosynthesis and ATP synthesis (F0F1 ATPase/ATP synthase).

Types of Membrane Proteins

  • Peripheral Membrane Proteins:

    • Loosely associated with membranes via ionic interactions.

    • Removed through ionic disruption (high salt or pH changes).

  • Integral Membrane Proteins:

    • Span the entire membrane with asymmetry similar to that of the membrane.

    • Can only be removed using detergents that disrupt the membrane.

Distribution of Membrane Proteins

  • Amino acids in membrane proteins cluster in distinct regions such as transmembrane segments, which are typically hydrophobic.

Lipid Anchors and Membrane Dynamics

Lipid-linked Proteins

  • Some membrane proteins are covalently linked to lipid molecules such as long-chain fatty acids, isoprenoids, and glycosylated phosphatidylinositol (PGI).

  • These anchors are reversible and allow for protein targeting to membranes.

PHYSICAL PROPERTIES OF MEMBRANES

  • Dynamic and flexible, capable of undergoing phase transitions.

  • Membranes are impermeable to large polar solutes and ions but permit small polar and nonpolar compounds through passive transport.

Membrane Composition Adjustments

  • Organisms can adjust membrane components to maintain fluidity, with fatty acid composition being a significant factor.

  • More fluid membranes require shorter and more unsaturated fatty acids.

  • Higher temperatures necessitate higher proportions of saturated fatty acids to maintain membrane integrity.

Table of Fatty Acid Composition in E. coli

  • The composition varies by temperature:

    • 10°C: 38% oleic acid

    • 20°C: 24% palmitoleic acid

    • 30°C: 29% palmitic acid

    • 40°C: 48% saturated palmitic acid

Membrane Rafts and Curvature

  • Lipid rafts contain clusters of glycosphingolipids with longer-than-usual tails; they are more ordered and facilitate protein segregation.

  • Proteins exert curvature on membranes through various modes:

    • Caveloins, intrinsic curvatures, or amphipathic helices crowd lipids in one leaflet.

Membrane Fusion

  • Fusion can be spontaneous or protein-mediated, retaining membrane continuity.

  • Examples include the entry of certain viruses and neurotransmitter release at synapses.

Transport Across Membranes

  • Cell membranes favor small nonpolar molecules through passive diffusion.

  • Transport proteins (transporters or permeases) facilitate the movement of polar molecules.

Types of Transport

  • Simple Diffusion: Nonpolar compounds move down concentration gradients.

  • Facilitated Diffusion: Movement down electrochemical gradients with the help of transport proteins.

  • Active Transport: Moves substances against electrochemical gradients, can be primary (using ATP directly) or secondary (coupled with ions).

Classes of Transport Systems

  • Uniport: Transports a single substance.

  • Symport: Transports two substances in the same direction.

  • Antiport: Transports two substances in opposite directions.

Glucose Transport Mechanisms

  • Utilizes both Na+-glucose symporter and glucose uniporter.

  • Transport occurs at opposing cellular sides, demonstrating asymmetry in protein distribution.

Special Transport Mechanisms

  • Bicarbonate Transporter: Functions as an antiporter to maintain electrochemical potential and facilitate CO2 transport into erythrocytes.

Active Transport Variants

  • Primary Active Transport: Directly uses ATP.

  • Secondary Active Transport: Indirectly utilizes energy stored in ion gradients.

Ion Channels and Conditions

  • Specific ion channels maintain concentrations across membranes.

  • Diseases associated with ion channels, such as cystic fibrosis, highlight the importance of functional integrity.

Summary of Key Points

  • Membranes comprise a selective bilayer, with varied lipid and protein compositions across organisms, tissues, and organelles.

  • Membrane proteins serve multiple roles, particularly in solute transport, with active transport requiring ATP and manifesting through various mechanisms.

Types of Integral Proteins - Integral proteins that span the membrane can be classified into several types based on their orientation and structural features:

  1. Type I Integral Proteins

    • Structure: Single pass, N-terminus oriented outside the cell (extracellular).

    • Examples: Glycoprotein hormones (like the insulin receptor).

  2. Type II Integral Proteins

    • Structure: Single pass, N-terminus oriented inside the cell (intracellular).

    • Examples: Certain receptors can be classified here.

  3. Type III Integral Proteins

    • Structure: Multiple transmembrane segments that span the membrane multiple times.

    • Examples: G protein-coupled receptors (GPCRs).

  4. Type IV Integral Proteins

    • Structure: Multi-protein complexes or bundles that span the membrane multiple times, often forming channels or pores.

    • Examples: Voltage-gated ion channels.

  5. Type V Integral Proteins

    • Structure: Lipid-anchored proteins that are not transmembrane but are associated with the membrane through lipid modifications.

    • Examples: Some adhesion molecules.

Functionality of Types:

  • Each type contributes to various cellular functions, such as transport, signaling, and communication, according to their orientation and interaction with other cellular components.