Lipids (McMurry Ch. 27) 27.1 Waxes, fats & oils 27.2 Soap & detergents 27.3 Phospholipids & sphingolipids 27.4 Prostaglandins, thromboxanes, leukotrienes 27.5 - 27.6 Isoprenoids Topics related to Part 1: trans and natural fats, omega-3 fatty acids and inflammation, HDLs, LDLs & cholesterol, lipid oxidation and antioxidants; COX activity & COX-1 and COX-2 inhibitors • The chemistry of lipids is all about how structure affects function. This is generally the case with biomolecules (true of carbohydrates, peptides, proteins) • Since the fats and oils are esters, their chemistry fits in well with the previous chapters on carboxylic acid derivatives; reactions of these molecules are similar • Other important lipids include prostaglandins, phospholipids, terpenes and steroids • We will discuss information that is not covered in the textbook. Take careful notes in class.

OWL homework* on this chapter is brief, and rather inadequate. Some supplemental HW problems listed below from the McMurry textbook should help: Chapter 27: 14, 17, 20, 22, 24, 25, 33, 35, 38, 46

Lipids: Structure, Function & Chemistry 1. Waxes (27.1) Structure: Esters of long-chain fatty acids and long-chain alcohols Function: Coatings, protection against environment Example: Carnauba wax (palm leaves) : CH3(CH2)30-COO-(CH2)33CH3 2. Fatty acids & Triacylglycerols (Fats & Oils—27.1–27.2) Fatty acid behavior & micelle formation was introduced in Ch. 21 Structure of fats & oils: glycerol backbone esterified with three fatty acids Function: Fatty acid storage, long-term source of energy, layer of insulation Structure & composition: see Table 23.1, 23.2, more details to follow 3. Phospholipids & Sphingolipids (Section 27.3) Structure: Glycerol or sphingosine backbone with phosphoesters, fatty acid esters, amides and/or sugars attached Function: Primary component of cell membranes 4. Prostaglandins & other eicosanoids (Section 27.4) Structure: Derivatives of arachidonic acid, a 20-C fatty acid Functions: Regulation of physiological processes, inflammatory response 5. Isoprenoids: Terpenoids & steroids (Essential oils, Hormones, Vitamins, etc.) Structure: Hydrocarbon chain & ring structures composed of isoprene units Functions: Many! Details in section 27.5 – 27.6 Physical properties of lipid classes: Behavior of lipids depends on polarity! Intermolecular forces play a vital role in the function & behavior of lipids. Hydrophobic = non-polar, comprised mainly of hydrocarbon chains, rings Hydrophobic structures tend to aggregate together Hydrophobic interactions = London dispersion forces Hydrophilic = polar structures, comprised of polar and charged functional groups such as – OH, – COOH, –CHO, –NH2, amides, -NR3+, – COOThese groups are attracted to and are soluble in water through dipole-dipole forces and hydrogen bonding interactions. Amphiphilic =

Structures which have both nonpolar areas and polar or charged areas. This will affect how these molecules aggregate together.

Fatty acids: Common long-chain carboxylic acids are shown in Table 27.1 Some key points about fatty acid structure & properties: 1) The number of C in the chain is always even - biosynthesis by condensation of decarboxylated malonyl esters adds 2 C pieces to growing chain. 2) Saturated fatty acids of 12 - 20 C are common; overall shape = straight

3) Unsaturated fatty acids in nature are always cis (Z) isomers; puts a “kink” in the chains & affects 3-D structure (trans-fatty acids only form synthetically) 4) As the number of double bonds increases (polyunsaturated) melting points decrease

Triacylglycerols (TAG, aka “triglycerides”) O H 2C HC H2 C

OH OH OH

+

HOOC

R1

HOOC

R2

HOOC

R3

H 2C

C

O

HC

O C

O O

H2 C O

R1

R2

C R3

Condensation of glycerol with three fatty acids produces a molecule of fat or oil Some key points about structure and properties of triacylglycerols 1) 2) 3) 4)

TAG that are solid at room temperature are classified as fats (animal-based) TAG that are liquid at room temp. are classified as oils (vegetable-based) In general, the more unsaturated the fatty acids in a TAG, the less solid it is Most liquid TAG come from plant sources (olives, corn, safflower)

5) Most solid or primarily saturated fats come from animal sources 6) 3-D structure of fatty acids affects packing which in turn affects melting point

Trans fatty acid is similar in shape to a saturated fatty acid. Unsaturated TAG doesn’t pack as tightly due to shape

C=C double bonds in nature: Natural fats contain fatty acids with double bonds in the cis or Z configuration.

Chemistry of TAG: a) Saponification: Base-catalyzed hydrolysis gives glycerol + fatty acid salts +

b) Hydrogenation: Rxn with H2/Pt converts unsaturated carbons to saturated

c) Catabolism: TAG undergo acid-catalyzed hydrolysis in stomach (digestion) Fatty acids break down 2 C at a time to acetyl-CoA which enters citric acid cycle (Figure 29.3) d) Lipid peroxidation and antioxidants

Polyunsaturated fatty acids are easily oxidized by O2 or oxygen free radicals: a peroxy radical

an alkyl hydroperoxide

Key point: Fatty acid oxidation contributes to cardiovascular disease. Oxidation of LDL initiates formation of “plaque” (solid buildup) in blood vessels and onset of atherosclerosis and heart disease. Fatty acids are a major component of:  Lipoproteins, especially LDL (low-density lipoproteins)  Cell membranes; oxidation degrades membranes and makes them less fluid  Oils and fats in food Oxidation of fatty acids causes “rancidity” - oxidative cleavage of unsaturated fatty acids is common, leads to shorter chain aldehydes and acids. Antioxidants are primarily compounds which react with free radicals (often by forming a more stable free radical) and remove them from the site before damage occurs. Many substituted phenols are antioxidants because they form a stable phenoxyl radical: OH

+

R

Some common antioxidants:

O

+ RH

Dietary fat and the human body Fats and cholesterol (in the form of fatty acid esters) are carried through the bloodstream and distributed to and from the tissues and organs by lipoproteins LDL:

Low density lipoproteins carry cholesterol from liver to rest of body High LDLs tend to deposit more lipid in blood vessels Lipids are subject to oxidation (see previous page) High LDL levels raise risk of atherosclerosis and heart disease

HDL:

High density lipoproteins carry cholesterol back to the liver They tend to scavenge lipids left behind High HDL levels lower cardiovascular disease risk

Effects of dietary fatty acids on serum cholesterol levels: Mono (MUFA) and polyunsaturated (PUFA): lower LDL/ raise HDL

Saturated fats: raise both LDL and HDL

Trans-fats (processed food): raise LDL

Omega-3-fatty acids (occur mainly in fish, nuts, seeds)

Good for your health! 1. Omega-3’s are generally highly unsaturated, so they lower LDLs, raise HDLs 2. Omega-3’s are thought to reduce inflammation throughout the body (see prostaglandins) Soaps:

Fatty acid salts & their physical behavior

“Saponification” = base-catalyzed formation of carboxylate salts from fats & oils NaOH 3 CH3(CH2)nCOO- Na+ + [CH3(CH2)nCOO]3-glycerol glycerol Key behavior: Micelle formation (see Ch. 21 notes) • Charged "head" interacts with water while nonpolar "tail" is repelled by water. • Tails” interact with each other through London dispersion forces ("hydrophobic" interaction) • The resulting spherical formation is called a "micelle" How soap works: Since most dirt is oil-based, it is attracted to the center of the micelle and the soap micelles therefore break up dirt particles (but remain soluble due to charged outer layer)

Phospholipids, sphingolipids and the structure of cell membranes

 Their major role is as a barrier between cells and their environment; separating the cytoplasm and cellular structures from the extracellular fluid and each other.  Both are classes of amphiphilic molecules, consisting of a charged or polar “head” and nonpolar hydrocarbon “tails”  A typical phospholipid (or phosphoacylglycerol) has a glycerol backbone with two fatty acid chains and a phosphate ester ending in a charged group (usually an amine) Lecithins (phosphatidylcholines) are one of the major components of cell membranes: Fatty acid structure varies; in “egg lecithin”, R1 = palmityl R2 = oleoyl Cephalins (phosphatidylethanolamine) & phosphatidylserine differ in amine structure Hydrolysis of a phospholipid produces: • glycerol • two fatty acids • phosphate • an amino alcohol Sphingolipids differ from other phospholipids by having a sphingosine backbone

Phospholipid “Bilayer” of cell membrane Phospholipids naturally arrange themselves in two layers with their hydrophobic tails pointing inward and their charged ends facing aqueous environment. Fatty acid ester composition varies; the more unsaturated the groups, the more “fluid” and flexible the cell membrane. Other components of cell membranes:  Cholesterol – a steroid member of the terpenoid class of lipids which lends rigidity to the animal cell membrane  Proteins – Various proteins in the membrane function to facilitate transport across the membrane (integral) or act as receptors for signaling molecules (peripheral)  Carbohydrates – Found on the surface of membranes as parts of glycoproteins. Some carbohydrate structures also function as receptors.

Sphingolipids Occurrence: Sphingolipids are found mainly in nerve and brain cell membranes.  Sphingomyelins make up the myelin sheath surrounding nerves  Cerebrosides (glycolipids) are found in brain tissue  Several human genetic diseases result from faulty metabolism or abnormal accumulation of sphingolipids in the body: o

Tay-Sachs disease – Accumulation of glycolipids in the brain due to lack of an enzyme (hexosaminidase A) required to metabolize glycolipids results in severe brain damage.

o

Niemann-Pick disease – Similarly, lack of an enzyme required to metabolize sphingomyelin (sphingomyelinase) results in overaccumulation in cells, severe neurological damage & malfunction of liver and spleen.

o

Multiple Sclerosis – Breakdown of the myelin sheath due to attack by cells of the immune system results in slowing of nerve impulses, eventual paralysis.

A sphingolipid structure: Normally, sphingolipids are metabolized to their components: sphingosine, fatty acids, sugars, phosphocholine, etc. Sphingolipids exhibit bilayer-formation like phospholipids; overall amphiphilic behavior

Predict the products of base-catalyzed hydrolysis of this phospholipid:

Prostaglandins and other eicosanoids: Biosynthesis and Functions  Linoleic acid arachidonic acid  Arachidonic acid is converted through a series of enzymatic and free radical rxns to prostaglandins (Fig. 27.5).  Prostaglandins and related compounds regulate a wealth of physiological processes 1) Prostaglandins – structural features

Precursors:

Biosynthesis: The enzyme endoperoxide synthase (consisting of cyclooxygenase and hydroperoxidase) converts arachidonic acid to PGH2, the precursor of all prostaglandins Functions and physiological effects: Regulation of blood pressure and reproductive functions; induce inflammation, fever and pain; inhibit platelet aggregation

Prostaglandins, COX-1 and 2, and Inflammation Most non-steroidal antiinflammatory drugs (NSAIDS) like aspirin and ibuprofen work by blocking the action of cyclooxygenase, thereby inhibiting prostaglandin production

2) Prostacyclin – Also made from PGH2 but contains a fused bicyclic structure Functions: Opposite of thromboxanes

3) Thromboxanes – Also produced from PGH2 but contain a 6-membered “oxane” ring

Functions: Platelet aggregation, clotting, constriction of blood vessels

4) Leukotrienes – Synthesized directly from arachidonic acid; 3 conjugated C=C bonds but no ring structure

Effects: Smooth muscle contraction, allergic response, lung constriction, swelling