Lipids

Chapter 29

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• Lipids are biomolecules that are soluble in organic solvents.• The identity of lipids is defined on the basis of a physical property and

not by the presence of a particular functional group.• Lipids share many properties with hydrocarbons.

Figure 29.1Three examples of lipids

Lipids

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• Lipids can be categorized as hydrolyzable and nonhydrolyzable.

[2] Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous hydrolysis.

[1] Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis with water. • Many hydrolyzable lipids contain an ester unit.

Hydrolyzability of Lipids

Waxes• Esters of High Mw alcohol and High Mw acid• Crystalline pure, plastic and malleable as mixtures

Spermacetti (whale oil) – buoyancy mechanism for diving (mix freezes at 30 °C)

Bees Wax (mp 60-64 °C), Carnauba (Brazil or palm) wax Cerotic acid C26 carboxylic acid

Mostly found as mixtures

Also jojoba wax (C36-C46 acids & alcohols)Sebum (includes 20-30% waxes)

EssentialFatty acids(no biosynthesis in humans)

Triglycerides (oils and fats)

•Fats melt above room temperature

•Oils melt below room temperature

•Unsaturated is always (Z) or (cis)

•Unsaturated have lower melting points than saturated

(butter is a solid, olive oil is a liquid)

•More unsaturation the lower the melting point.

Triglycerides: Cocoa butter

Mixture of triglycerides Melts 34 °C (in your mouth)

Oleic, palmitic, steric esters

Fish oils (cod liver and herring oils) unsaturated to remain liquid in cold water

Hydrolysis of Triglycerides

Mechanism for hydrolyses?

Reactions of unsaturated fatty esters• Hydrolysis, transesterification• Reduction of C=C

• Allylic Oxidations

Phospholipids (hydrolyzable)phosphoacylglycerols

sphingomyelins

phosphatidylethanolamine or cephalin

phosphatidylcholine or lecithin

derivatives of the amino alcohol sphingosine

myelin sheath around nerves is rich in sphingomyelins

3D Structure of Phosphoacylglycerols

Fat soluble Vitamins: A & D• organic compounds required in small quantities for normal metabolism. Not synthesized by organism. Must come from diet.

intestinal absorption of calcium and phosphateDeficiency: Rickets

Deficiency: Night blindness

Fat soluble Vitamins: E & K

Blood clottingDeficiency: excessive bleeding

Deficiency: neurological problemsAntioxidant

Eicosanoids• group of potent biologically active compounds containing 20

carbon atoms derived from arachidonic acid.• prostaglandins, leukotrienes, thromboxanes, and prostacyclins• Autocrine or paracrine hormones

Lower blood pressureInhibit platelet aggregationControl inflammationLower gastric secretionsInduce laborControl cell growthControl calcium transportSensitizes spinal neurons to pain

Constrict blood vesselsTrigger platelet aggregation

Dilate blood vesselsInhibit platelet aggregation

Constrict smooth muscle (lungs)

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• Prostaglandins themselves are unstable in the body, having a half-life of only minutes.

• Thus, more stable analogues have been developed that retain their biological activity for longer periods.

• An example is misoprostol, an analogue of PGE1, which is sold as a mixture of stereoisomers.

• Misoprostol is administered to prevent gastric ulcers in patients who are at high risk of developing them.

Prostaglandin Analogs

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Figure 29.7The conversion of arachidonic

acid to prostaglandins,thromboxanes, prostacyclins,

and leukotrienes

Synthesis of Eicosanoids

•Aspirin and other non-steroidal anti-inflammatory drugs (NSAID) inactivate COX 1 & 2 enzymes• results in an increase in gastric secretions

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• A group of anti-inflammatory drugs that block only the COX-2 enzyme were developed in the 1990’s.

• These drugs—rofecoxib, valdecoxib, and celecoxib—do not cause an increase in gastric secretions, and were thus believed to be especially effective for long-term use in patients with arthritis.

• Unfortunately, both rofecoxib and valdecoxib have been removed from the market, since their use has been associated with increased risk of heart attack and stroke.

COX-2 Inhibitors

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• Terpenes are lipids composed of repeating five-carbon units called isoprene units.

• An isoprene unit has five carbons: four in a row, with a one-carbon branch on a middle carbon.

• Terpenes can be cyclic or acyclic, and may contain heteroatoms.

Terpenes

Indentifying terpenes

Squalene in sebaceous oils

Terpene biosynthesis (carbocation chemistry)

Terpene biosynthesis

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All other terpenes are formed from farnesyl and geranyl diphosphates

Formation of cyclic terpenes

Steroids

Cholesterol8 chiral centers28 =256 possible stereoisomers

biosynthesis in the body from squalene (C30).

HormonesSurfactants (membranes)Oils

Biosynthesis of Cholesterol

More stable

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• Several drugs are now available to reduce the level of cholesterol in the bloodstream.

• These compounds act by blocking the biosynthesis of cholesterol in its early stages.

• Two examples are atorvastatin (Lipitor) and simvastatin (Zocor).

Figure 29.12

Cholesterol-Lowering Drugs

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Steroidal Sex Hormones

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• Synthetic analogues of these steroids have found important uses, such as in oral contraceptives.

• Synthetic androgen analogues, called anabolic steroids, promote muscle growth.

• Although they are used by athletes, their use is not permitted in competitive sports.

Synthetic Hormone Steroids

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• A second group of steroid hormones includes the adrenal cortical steroids.

• Examples are cortisone, cortisol, and aldosterone.• All of these compounds are synthesized in the outer layer of the adrenal

gland.• Cortisone and cortisol serve as anti-inflammatory agents and they also

regulate carbohydrate metabolism. • Aldosterone regulates blood pressure and volume by controlling the

concentration of Na+ and K+ in body fluids.

Adrenal Cortical Steroids

Lanolin

“lana” wool

“Olin” from oleum for oil

5-25 wt% of wool is lanolin oil

40% alpha hydroxyestersNo triglyceridesWaxesCholesterol estersSebaceous glands

R = C10-C22