Lipids and Their Functions

Lipids

• Lipids are distinguished by their high solubility in non-polar solvents and low solubility in water (H₂O).
• Lipids are a diverse group of compounds including fats, oils, waxes, some vitamins, hormones, and most non-protein components of membranes.
• Lipids are amphipathic molecules, possessing both polar and nonpolar regions.
• Lipids serve as major components of biological membranes, storing energy, and acting as hormones.
• They are major components of biological membranes, define the basic unit of life (cell) and subcellular compartments (eukaryotes), and include cholesterol.
• Lipids are a major form of stored energy in biological systems; complete oxidation of lipids generates more energy than sugars.
• Lipids act as hormones, enabling signal transduction (communication) between cells.

Lipid Classification - Key Concepts 1

• The length and saturation of a fatty acid chain define its physical properties.
• Triacylglycerols and glycerophospholipids contain fatty acids esterified to glycerol.
• Sphingolipids resemble glycerophospholipids but may have large carbohydrate groups.
• Steroids, isoprenoids, and other lipids have a wide variety of functions.

Fatty Acids - Properties

• Fatty acids are carboxylic acids with long-chain hydrocarbon side groups.
• In higher plants and animals, 16- and 18-carbon fatty acids (palmitic, oleic, linoleic, and stearic acids) are dominant.
• Most fatty acids have an even number of carbon atoms because they arise from the concatenation of C₂ units.
• Saturated fatty acids lack double bonds, while unsaturated fatty acids have one or more double bonds (mostly cis configuration).
• Polyunsaturated fatty acids have multiple double bonds.

Saturated vs. Unsaturated Fatty Acids

• Saturated fatty acids (no double bonds) pack together efficiently, resulting in higher melting points and decreased fluidity.
• Unsaturated fatty acids (containing double bonds) pack less efficiently, leading to lower melting points and increased fluidity.
• Cis double bonds create bends in the fatty acid chain, further decreasing the melting point.

Triacylglycerols

• Triacylglycerols (triglycerides) are glycerol molecules esterified to three fatty acids.
• They are nonpolar and water-insoluble substances functioning as energy reservoirs.
• Triacylglycerols differ based on the identity and placement of their three fatty acid residues.

Glycerophospholipids

• Glycerophospholipids (phosphoglycerides) are major components of biological membranes.
• They consist of glycerol-3-phosphate with fatty acids esterified at positions C1 and C2.
• A phosphate group is attached to a polar head group (X), making them amphiphilic.
• Phosphatidic acids are the simplest glycerophospholipids.
• Common glycerophospholipid head groups include choline, ethanolamine, serine, and inositol.

Sphingolipids

• Sphingolipids are major membrane components, derived from the amino alcohol sphingosine.
• Ceramides are the parent compounds of sphingomyelins, cerebrosides, and gangliosides.
• Sphingomyelins contain a phosphocholine head group.
• Cerebrosides contain a single sugar residue (e.g., glucose or galactose).
• Gangliosides are complex glycosphingolipids with multiple sugar residues, including sialic acid.

Steroids

• Steroids are derivatives of cyclopentanoperhydrophenanthrene and have four fused non-planar rings.
• Cholesterol is the most abundant steroid in animals, classified as a sterol due to its C3-OH group.
• It is a major component of animal plasma membranes (~30-40 mol%).
• The polar OH group of cholesterol gives it a weak amphiphilic character.
• Cholesterol is important for membrane fluidity.
• Steroids undergo esterification with long-chain fatty acids, forming cholesteryl esters like cholesteryl stearate.

Steroid Hormones

• Steroid hormones, derived from cholesterol, regulate various physiological processes.
• These are classified according to their function:
  • Glucocorticoids (e.g., cortisol): affect carbohydrate, protein, and lipid metabolism.
  • Mineralocorticoids (e.g., aldosterone): regulate salt and water balance.
  • Androgens (e.g., testosterone): affect sexual development.
  • Estrogens (e.g., estradiol): affect sexual development and function.

Membrane Structure

• Certain amphiphilic molecules form bilayers.
• Bilayers are fluid structures where lipids diffuse laterally.
• The fluid mosaic model describes the dynamic arrangement and interactions of membrane lipids and proteins.
• The membrane skeleton provides shape and flexibility.
• Lipids are not distributed uniformly, and can form rafts.
• The secretory pathway depicts the membrane and secreted protein transmembrane passage.
• Different types of coated vesicles transport proteins.
• SNAREs bring membranes together mediating vesicle fusion.

Integral Membrane Proteins

• Integral membrane proteins have transmembrane regions consisting of alpha-helixes or beta-barrels.
• They are tightly associated with the membrane and are sometimes embedded into the membrane.
• Lipid-linked proteins are covalently attached to prenyl groups, fatty acyl groups, or glycosylphosphatidylinositol.
• Peripheral membrane proteins interact noncovalently with other proteins or lipids.

Bilayer Formation and Properties

• Bilayer formation, driven by the hydrophobic effect, involves amphiphilic molecules arranging with their hydrophobic tails facing each other and their hydrophilic heads facing the water.
• Lipid bilayers have fluidlike properties, meaning lipids can diffuse laterally within the membrane. This lateral diffusion is rapid.
• Transverse diffusion (flip-flop) is extremely slow.

Membrane Skeleton

• The membrane skeleton underlies the plasma membrane creating a dense, irregular network of proteins (spectrin, ankyrin, actin, etc).
• Spectrin: a major component of the meshwork, consists of 2 polypeptide chains with similar structure, providing flexibility while contributing to cell shape.
• Ankyrin: anchors the membrane skeleton to the integral membrane proteins, typically ion channels.
• This structural meshwork gives the cell its shape.

Gates and Fences Model

• The interaction of integral membrane components with cytoskeletal proteins explains how proteins can exhibit various degrees of membrane mobility.
• Integral proteins interacting with the cytoskeleton remain immobile.
• Other integral proteins can rotate or diffuse.
• Cytoskeletal components can create "gates" allowing proteins to move.

Other techniques

• Fluorescence Recovery After Photobleaching (FRAP): used for measuring lipid and protein diffusion within cellular membranes.
• Photobleaching: involves temporarily inactivating a fluorescent molecule utilizing a focused laser beam.
• The rate at which the bleached area recovers fluorescence indicates the rate of diffusion.

Diseases

• Disorders of ganglioside breakdown (e.g., Tay-Sachs disease) can cause serious neurological deterioration.