CHE414 Lecture 20 (Membranes; F24)

Lecture Overview

  • Lecture 20: More Lipids and Membranes

  • Announcements: Prelab, lab report, and quiz next week.

  • Reminder: Mole Day (10/23) next Wednesday.

  • Light-hearted comment: "Did you hear about the explosion at the cheese factory?"

Sphingolipids

  • Structure: Sphingolipids use sphingosine, not glycerol, as a backbone.

  • Importance: Major membrane component; especially abundant in the central nervous system.

  • Ceramide Formation: A second fatty acyl group attaches via an amide bond to the serine nitrogen (ceramide).

  • Head Group: Comes from the hydroxyl oxygen of serine.

Sphingomyelin

  • Definition: Most common type of sphingolipid.

  • Relation to Phosphoglycerides: Similar structure.

  • Function: Found in the membranous myelin sheath surrounding nerve axons, providing electrical insulation.

Cerebrosides

  • Definition: A type of sphingolipid with a monosaccharide head group (glycosphingolipid).

  • Characteristics: Lack phosphate groups, making them nonionic.

  • Location: Found in nerve cell membranes, including myelin sheaths.

Gangliosides

  • Definition: Sphingolipids with oligosaccharide head groups.

  • Characteristics: Associated with cell-surface membranes; significant fraction of brain lipids.

  • Biological Role: Responsible for ABO blood types.

Fascinating Features of Gangliosides

  • Receptors: Oligosaccharides act as cell receptors for hormones and bacterial toxins (e.g., cholera toxin).

  • Cell Functions: Involved in cell-cell recognition, differentiation, and growth (cancer).

  • Tay-Sachs Disease: Disorder linked to the metabolism of gangliosides, leading to lysosomal swelling and tissue enlargement in the nervous system.

Cholera Toxicity Mechanism

  • Binding: Carbohydrates on intestinal epithelial cells act as binding sites for cholera toxin.

  • Effect: Toxin interferes with signaling pathways, resulting in fluid efflux into the intestine, causing dehydration.

Cholesterol and Steroids

  • Structure: Derivatives of cyclopentanoperhydrophenanthrene; four fused nonpolar rings.

  • Cholesterol: A well-known steroid found in biological membranes.

  • Functions: Precursor for steroid hormones (estrogen, testosterone) and fat-soluble vitamins (A, D, E, K).

  • Amphipathic Nature: While amphipathic, its ring structure is rigid.

Other Lipids

  • Waxes: Protect plants from desiccation; form water-impermeable barriers.

  • Spices: Lipids such as capsaicin, cloves, and cinnamon.

  • Eicosanoids: Regulate blood pressure, pain, fever, and blood coagulation.

Nutritional Study Findings

  • Study Insight: Volunteers consuming avocado-rich salads showed increased beta-carotene in blood samples.

  • Conclusion: Avocado's monounsaturated lipids may enhance absorption of lipid-soluble nutrients, like beta-carotene, which converts to vitamin A.

Fatty Acids and Lipid Structures

  • Familiarity required with structures of palmitate, stearate, oleate, linoleate, triacylglycerol, and glycerophospholipid.

  • Recognize structures of sphingolipids and cholesterol.

Lipid Bilayer Characteristics

  • Formation: Lipid bilayers form spontaneously and are stable and self-sealing.

  • Composition: Made of mixtures of various lipids; no defined geometry.

  • Thickness: Total thickness of 30-40 Å, hydrophobic core 25-30 Å thick.

  • Dynamics: Not static; head groups bob up and down while tails move rapidly.

Lipid Bilayer Fluidity and Composition

  • Types of Lipids: Fatty acids, glycerophospholipids, triacylglycerols, and sphingolipids can form bilayers.

  • Fluidity: Melting point varies with acyl chain length and saturation; more unsaturation leads to greater fluidity.

  • Mobility: Longer acyl chains are less mobile; organisms adapt their lipid composition to maintain membrane fluidity in colder temperatures.

Membrane Asymmetry

  • Leaflet Composition: Two leaflets of a bilayer rarely have the same lipid composition; carbohydrate groups usually face the extracellular space.

  • Functional Importance: Distinct lipid arrangements play critical roles in cellular processes.

Diffusion in Membranes

  • Diffusion Types: Transverse diffusion is slow; lateral diffusion is fast (7 changes per second).

  • Mechanisms: Involves proteins called flippases and floppases for maintaining lipid distribution.

Proteins in Biological Membranes

  • Composition: Biological membranes are approx. 50% protein by weight.

  • Variation: Different membranes (like RBCs and mitochondria) have contrasting lipid-to-protein ratios.

Membrane Protein Types

  • Integral Proteins: Span the lipid bilayer; hydrophobic within the membrane and hydrophilic on exposed regions.

  • Peripheral Proteins: Loosely associated, mainly interact with polar head groups; can be easily removed.

  • Lipid-anchored Proteins: Have covalent lipid attachments; tethered to the membrane without interacting with lipid cores.

Integral Membrane Protein Structures

  • Alpha Helices: Composed of hydrophobic residues, facilitating mingling with acyl chains.

  • Beta Barrels: Can involve multiple strands; functionally important channels with openings on either side of the membrane.

Analyzing Protein Anchor Types

  • Myristoylation, Palmitoylation, Prenylation: Lipid modifications allow tethering of proteins to membranes, often through Cys residues.

The Fluid Mosaic Model

  • Concept: Membrane proteins float in a lipid sea; they don't freely move across the bilayer; there are limitations on mobility.