Biochemistry Lipid Properties Quiz

Membrane Structure

• Biological membranes are composed of lipid bilayers that are impermeable to polar or charged molecules.
• The hydrophobic effect drives membrane formation of amphipathic molecules.
• Membranes are asymmetric and composed of lipids and proteins, which may or may not have carbohydrates covalently bound.
• Membrane proteins play key roles in transport and transduction of information across the membrane.

Essential Membrane Functions

• Act as a barrier regulating the import and export of essential molecules.
• Compartmentalization of specialized processes increases cellular efficiency.
• The cell membrane modulates cell-cell recognition due to the presence of glycoproteins and glycolipids.
• Signaling across the membrane is mediated by proteins and lipids.
• The structure of a membrane is key for its function.

Membrane Formation

• An increase in entropy of the membrane is responsible for membrane formation.
• Covalent bond formation between proteins and lipids.
• A decrease in ionic interactions with water.

Membrane Properties

• Biological membranes are composed of lipid bilayers with hydrophobic and hydrophilic properties.
• The hydrophobic effect drives membrane formation of amphipathic molecules.
• Membranes are asymmetric, composed of lipids and proteins, and may have carbohydrates attached to them.
• Membrane proteins are crucial for transporting and transducing information across the membrane.

Membrane Fluidity

• Proteins carry out the movement of molecules across the membrane.
• Signals can be transmitted across a membrane.
• Conformational changes are important for mediating processes such as signal transmission.
• Lipids and cholesterol contribute to membrane fluidity.

The Fluid Mosaic Model

• Proposed in the early 1970s by Singer and Nicolson.
• Membrane components can move rapidly in the plane of the membrane.
• Contains a diverse mixture of lipids, embedded and peripheral proteins, and carbohydrates on the surface.
• Recent modifications reveal differences in lipid and membrane protein movement in pure lipids and biological membranes.

Measuring Lipid Dynamics in Membranes

• How fast lipids and proteins diffuse laterally in a membrane can be measured using a method called lateral diffusion.
• One measure called Fluorescence Recovery After Photobleaching (FRAP) can show the movement of molecules in a membrane.

Membrane Dynamics

• The recovery of lipids and membrane proteins using FRAP demonstrates their mobility in the plane of the membrane.
• Lipids can move very quickly (approximately 1 μm/s).
• Single-molecule tracking fluorescence microscopy monitors the movement of fluorescent molecules throughout the membrane.
• Some proteins or lipids may spend more time interacting within certain regions such as lipid rafts.
• The lateral diffusion of proteins may depend on interactions with other proteins (e.g., cytoskeleton) or extracellular components.

Detergents and Crosslinkers in FRAP Experiments

• SDS (sodium dodecyl sulfate) uniformly charges, disrupts cell and denatures proteins.
• Crosslinkers covalently link proteins, affecting FRAP recovery rate.

Biological Membranes Are Asymmetric

• The two leaflets of the membrane have very different lipid and protein compositions.
• The addition of sugars to lipids and proteins is a form of post-translational modification.
• The movement of lipids from one leaflet to the other is very slow.
• Flip-flow diffusion of polar/charged groups across the interior is energetically unfavorable.

Enzymes Mediate Membrane Asymmetry

• Uncatalyzed transbilayer diffusion is very slow.
• Catalyzed transbilayer translocation, ATP-dependent, requires enzymes like Flippases, Floppases, and Scramblases.
• Various enzymes can also be ATP-independent.

Membrane Asymmetry

• Enzymes assist with the heterogeneous distribution of lipids and proteins on either side of the lipid bilayer.
• ATP hydrolysis of flippases and floppases helps drive the movement of lipids.
• Scramblases move all lipids down their concentration gradient, producing symmetrical membranes.
• Enzymes add oligosaccharides to proteins and lipids on the extracellular surface.

Lipids

• Lipids are a diverse class of molecules involved in providing structural support, storage of energy, and in signalling.
• Their physical properties are due to diverse chemical structures and functional groups. .
• Hydrophobic (non-polar) OR amphipathic (both polar and non-polar).

Lipid Self-Assembly and Bilayer Formation

• Lipids spontaneously aggregate in water to bury their hydrophobic groups while allowing polar groups to interact with water.
• Non-covalent forces (hydrophobic effect, H bonds, Van der Waals packing) are the driving force for assembly.

Biological Lipids

• Categorize lipids by storage, structural, and signalling functions.
• Examples include triacylglycerols, phospholipids, sphingolipids, glycolipids, and sterols.

Fatty Acids

• Fatty acyl chains are either saturated or unsaturated and are numbered relative to the carboxylic acid or methyl group
• They can be free fatty acids (FFAs) or bound to a head group.

Fatty Acid Nomenclature

• Describe the carbon skeleton, number of double bonds.
• Naming conventions exist (e.g., n-Octadecanoic acid, cis-Δ9-Octadecenoate).

Omega Fatty Acids in Human Health

• Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids essential for humans.

Good and Bad Fats

• Omega fatty acids are good fats; essential for human health.
• Saturated and trans fats are considered bad fats.

Chain Saturation and Membrane Fluidity

• Saturated fatty acids form many non-covalent interactions, lower fluidity, and higher melting temperature.
• Unsaturated fatty acids have weaker interactions, higher fluidity, and lower melting temperature.

Phase Transitions

• Melting of membrane lipids involves a phase transition from gel-like solid to liquid crystalline phase.
• Melting temperature (Tm) is an index of membrane fluidity.
• Lipid samples have sharp transition temperatures, while native membranes show more broad peaks.

Triacylglycerols (TAGs)

• Efficient carbon-chain energy reserves.
• Dehydrated storage form primarily in adipocytes.
• Composed of 3 fatty acids bound to a glycerol backbone through ester linkages.
• Fatty acyl tails may contain double bonds creating mixed triglycerides.

Membrane Lipid Diversity

• Amphipathic molecules have polar head groups and apolar (hydrophobic) tails.
• Glycero-phospholipids have glycerol and phosphate headgroups and lipid tails.
• Sphingolipids have sphingosine backbone, fatty acid tails, and polar headgroups.
• Cholesterol is the most common membrane steroid.

Glycerophospholipids vs. Sphingolipids

• Glycerophospholipids have polar head groups that vary in charge.
• Sphingolipids (e.g., sphingomyelin, gangliosides) have different head groups from glycerophospholipids.

Cholesterol

• Can be metabolized into hormones and bile salts needed for dietary lipid absorption.
• Forms complex with sphingolipids and glycolipids for lipid rafts that moderate membrane fluidity. modulates membrane packing.

Proteins

• Peripheral membrane proteins are associated with the membrane by non-covalent interactions.
• Integral membrane proteins span the membrane.
• Lipid-anchored proteins have hydrophobic tails attached to membrane.

Peripheral Membrane Proteins

• Adhere to the surface of lipid membranes through non-covalent interactions.
• Can be removed using milder conditions like changing salt or pH.

Integral Membrane Proteins

• Completely span the membrane via transmembrane segments (TMs).
• Require harsh conditions (detergents or organic solvents) for purification.

Lipid-Anchored Proteins

• Have lipid chains covalently attached to amino acid functional groups and side chains.
• Examples include N-myristoylation and S-palmitoylation.
• GPI-anchored proteins linked by a sugar chain to phosphatidylinositol.

Membrane Protein Purification

• Studying membrane proteins needs extra consideration for purification and analysis.
• Some proteins can be removed with milder conditions like changing pH.
• Detergents isolate membrane proteins by creating micelles around hydrophobic regions.

Studying Membrane Proteins

• Detergents are amphipathic and help in solubilizing membrane proteins.
• Critical micelle concentration (CMC) is the concentration where detergents spontaneously form micelles.

Predicting Membrane Spanning Segments

• DNA sequencing and protein algorithms are used to deduce primary sequences of transmembrane segments (TMs).
• TMs primarily contain hydrophobic amino acids; ~20 amino acids needed to span the membrane.

Kyte-Doolittle Hydropathy Scale

• Used to determine hydropathy index of amino acid sequences for membrane protein prediction.

Determining Protein Topology

• Evaluate hydropathy index of amino acid sequences to determine protein topology.
• Use sliding window size for better sequence analysis result, and plot hydropathy indices to identify potential transmembrane segments.

Identifying Transmembrane Segments

• Methods used to identify transmembrane segments include analyzing glycophorin A and bacteriorhodopsin.

Generating Hydropathy Plots

• Automated programs like DeepTMHMM and SOSUI can generate hydropathy plots. Tools like SIB (ExPASy), Protscale, and TM-Finder are additional option.

Key Messages

• Biological membranes are assemblies of amphipathic molecules held together by non-covalent interactions.
• They are heterogeneous mixtures of lipids and proteins.
• Membranes have enzymes responsible for creating asymmetry within or across the lipid bilayer.
• Membranes are fluid and contain proteins that span the membrane.
• Proteins can be extracted for study using different techniques such as detergents, salts, and chaotropic agents.

Test your knowledge on the properties and behaviors of lipids in this biochemistry quiz. Explore topics such as fluidity, melting temperature, and lipid interactions. Determine the key roles and characteristics that define lipid structure and function.