Lipids Notes

Lipids

• Diverse group of hydrocarbon-based molecules.
• Highly soluble in organic solvents; limited solubility in aqueous solutions.
• Non-covalent association leads to a strong tendency to associate in aggregates.

Important Lipids for Human Cells:

• Fats or triacylglycerols (a.k.a. triglycerides).
• Phospholipids (e.g., lecithin).
• Cholesterol and cholesterol esters.
• Fat-soluble vitamins (A, D, E, K).

Physiological Functions of Lipids:

• Fuel molecules (free fatty acids).
• Energy stores (triacylglycerols).
• Barrier between aqueous compartments: Membrane bilayers contain phospholipids, glycolipids, and cholesterol.
• Hormones:
  • Cholesterol → steroid hormones
  • Arachidonic acid → prostaglandins, leukotrienes
• Intracellular second messengers (diacylglycerol, ceramide).

Fatty Acids:

• Contain a carboxylate group attached to a long hydrocarbon chain.
• Fatty acids are ionized at physiological pH. (Stearic acid → stearate).
• Some fatty acids have one or more double bonds, usually in the cis configuration.

Fatty Acids and Micelles:

• Ionized fatty acids are amphipathic, possessing both hydrophilic and hydrophobic portions, resulting in limited solubility in water.
• In aqueous solutions, fatty acids aggregate into micelles where long hydrocarbon chains associate with each other, leaving the charged carboxylate groups on the surface.
• In plasma (and serum), fatty acids are bound to the protein albumin.

Fatty Acid Nomenclature:

• Trivial names (e.g., stearate) exist for most fatty acids.
• Scientific names (e.g., octadecanoate) describe the number of carbons (C18).
• Unsaturated fatty acid designations include:
  • Number of carbons: number of double bonds (e.g., oleate is 18:1).
  • Position of double bonds (e.g., oleate is cis-Δ9 18:1 (ω9)):
    • cis-Δ9 locates double bond from carboxyl end.
    • ω9 locates the first double bond counting from the ω end of the molecule.
• The ω notation is particularly useful for ω6 and ω3 polyunsaturated fatty acids.

Fatty Acid Chain Length:

• Increased chain length → decreased solubility.
• Dietary and membrane fatty acids are usually 16-20 carbons long.
• Milk fat contains short and medium-chain fatty acids.
• Certain neural and retinal membranes are particularly rich in very long-chain polyunsaturated fatty acids with 22 or more carbons.

Double Bonds & Solubility:

• Double bonds increase fatty acid solubility and decrease the melting point.
• Examples:
  • Stearic Acid (18:0): Melting point 70°C, Spatial Width 0.25 nm
  • Oleic Acid (c-18:1(n-9)): Melting point 16°C, Spatial Width 0.72 nm
  • Linoleic Acid (c,c-18:2(n-6)): Melting point -5°C, Spatial Width 1.13 nm

Common Polyunsaturated Fatty Acids (PUFA):

• C18 PUFA:
  • Linoleate
  • α-linolenate
• C20 PUFA:
  • Arachidonate
• Linoleate and α-linolenate must be obtained in the diet.
• Arachidonic acid (20:4 ω6) can be synthesized by elongation and desaturation of linoleate (18:2 ω6).

Triacylglycerols: Fatty Acid Stores:

• Glycerol is a three-carbon molecule with three hydroxyl groups.
• Triacylglycerols (aka triglycerides) contain three fatty acids esterified to a glycerol backbone.
• Triacylglycerols are completely non-polar and hydrophobic, separating out of aqueous solution and forming lipid droplets in cells.
• Lipases are enzymes that hydrolyze triacylglycerols and are found within cells as well as in the digestive tract.

Phospholipids:

• Major class of membrane lipids.
• All phospholipids contain:
  • Two fatty acids that provide the hydrophobic barrier of the membrane.
  • A small polar molecule with an alcohol group esterified to a phosphate. This polar head group is hydrophilic and associates with the aqueous environment.
• Most phospholipids contain a glycerol backbone and are called phosphoglycerides.

Common Polar Head Groups of Phospholipids:

• Ethanolamine: two-carbon molecule with a hydroxyl group on one carbon and an amino group on the other.
• Choline: similar to ethanolamine but larger, where the modified amino group contains three methyl groups (CH_3-) instead of the three hydrogen atoms.

Phosphatidylethanolamine:

• Phospholipids like phosphatidylethanolamine are amphipathic: hydrocarbon chains of the two fatty acids are hydrophobic; the rest of the molecule is hydrophilic.
• Phosphatidylethanolamine is a zwitterion: the negative charge is on the phosphate group while the amine group of the ethanolamine has a positive charge.

Other Common Polar Head Groups:

• Serine: the alcohol group of phosphatidyl serine is part of an amino acid.
• Inositol: a six-carbon cyclic sugar derivative. Both serine and inositol contain a hydroxyl group which is esterified to the phosphate during phospholipid synthesis.

Sphingolipids:

• Have a sphingosine backbone.
• Sphingosine is structurally similar to a glycerol attached to a long chain fatty acid but with an amino group instead of one of the hydroxyls.
• Ceramide is formed by attachment of a fatty acid to the amino group.
• With its two long hydrocarbon chains, ceramide is similar in size and physical properties to a diacylglycerol.

Sphingomyelin:

• A choline phospholipid that is formed by the addition of a phosphate and a choline to the ceramide.
• Although the name reflects its high levels in the myelin sheath that surrounds nerves, it is present in all cells.
• Sphingomyelin is structurally similar to phosphatidyl choline, but the hydrocarbon chains are usually more saturated, conferring distinct properties on membrane domains.

Glycolipids:

• Formed by the addition of one or more sugar moiety to ceramide.
• The sugar(s) replace the phosphocholine as the polar head group.
  • Cerebrosides: ceramide + one sugar.
  • Gangliosides: ceramide + complex, often branched, carbohydrate chain.

Phospholipids and Bilayers:

• The favored structure for most phospholipids and glycolipids in solution is a bimolecular sheet rather than a micelle.
• Formation of lipid bilayers occurs rapidly and spontaneously in water.
• Lipid bilayers close on themselves to form compartments or vesicles.

Cholesterol:

• A lipid molecule with four linked hydrocarbon rings. It has a hydroxyl group at one end and a nonpolar hydrocarbon tail at the other.
• An essential component of mammalian cell membranes.
• The precursor for steroid hormones such as estrogen, testosterone, and cortisol.

Cholesterol Storage:

• Cholesteryl esters are completely non-polar molecules formed by esterification of a fatty acid to the hydroxyl group of cholesterol.
• Steroidogenic cells store cholesteryl esters in cytoplasmic lipid droplets.
• Like triacylglycerols, which are also non-polar, cholesteryl esters are not found in membranes.

LDL and Cholesterol Delivery:

• Lipoprotein particles in plasma serve to transport non-polar cholesteryl esters and triacylglycerols.
• LDL or low-density lipoprotein delivers cholesterol to cells.
• The core of the LDL particle is primarily cholesteryl esters.
• The amphipathic surface contains phospholipids, unesterified cholesterol, and a large protein known as apo B-100.

Vitamins as Lipids:

• Vitamin A derivatives have hormone-like effects on cell differentiation.
• Both β-carotene (provitamin A) and α-tocopherol (vitamin E) have anti-oxidant activity.