Lipid Notes

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

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

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

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

Most fatty acids have trivial names (e.g., stearate).
Scientific names (e.g., octadecanoate) describe the number of carbons (e.g., C18).
Unsaturated fatty acid designations:
- Expressed as "number of carbons: number of double bonds".
  - Oleate is 18:1.
- Position of double bonds:
  - Oleate is cis- $\Delta$ 9 18:1 ( $\omega$ 9).
  - cis- $\Delta$ 9 locates the double bond from the carboxyl end.
  - $\omega$ 9 locates the first double bond counting from the $\omega$ end of the molecule.
  - The $\omega$ notation is particularly useful for $\omega$ 6 and $\omega$ 3 polyunsaturated fatty acids.

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

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

C18 PUFA:
- Linoleate
- $\alpha$ -linolenate
C20 PUFA:
- Arachidonate
Linoleate and $\alpha$ -linolenate must be obtained in the diet.
Arachidonic acid (20:4 $\omega$ 6) can be synthesized by elongation and desaturation of linoleate (18:2 $\omega$ 6).

Glycerol is a three-carbon molecule with three hydroxyl groups.
Triacylglycerols contain three fatty acids esterified to a glycerol backbone.
Triacylglycerols are non-polar and hydrophobic, forming lipid droplets in cells.
Lipases are enzymes that hydrolyze triacylglycerols and are found within cells and in the digestive tract.

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

Choline and ethanolamine are common polar head groups of phospholipids.
Ethanolamine is a two-carbon molecule with a hydroxyl group on one carbon and an amino group on the other.
Choline is similar to ethanolamine but larger; the modified amino group contains three methyl groups (CH3-) instead of the three hydrogen atoms.

Phospholipids such as phosphatidylethanolamine are amphipathic.
- The 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.

Serine and inositol are other common polar head groups.
The alcohol group of phosphatidyl serine is part of an amino acid.
Inositol is a six-carbon cyclic sugar derivative.
Both serine and inositol contain a hydroxyl group (shown in red) which is esterified to the phosphate during phospholipid synthesis.

Sphingosine backbone: Structurally similar to a glycerol attached to a long chain fatty acid. It has 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.

Formed by addition of a phosphate and a choline to 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.
The hydrocarbon chains are usually more saturated, conferring distinct properties on membrane domains.

Formed by 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

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.

Lipid molecule with four linked hydrocarbon rings, a hydroxyl group at one end, and a nonpolar hydrocarbon tail at the other.
Essential component of mammalian cell membranes.
Precursor for steroid hormones such as estrogen, testosterone, and cortisol.

Lipoprotein particles in plasma transport non-polar cholesteryl esters and triacylglycerols.
LDL (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.

Vitamin A derivatives have hormone-like effects on cell differentiation.
Both $\beta$ -carotene (provitamin A) and $\alpha$ -tocopherol (vitamin E) have anti-oxidant activity.