Biomolecules Survey Part 2: LipidsLecture Supplement page 228

CH3(CH2)23CH2 O

O

CH2(CH2)28CH3

Myricyl cerotatePresent in beeswax, carnauba wax

•Nonpolar: Hydrophobic (“water hating”) or lipophilic (“fat loving”)•Polar: Hydrophilic (“water loving”) or lipophobic (“fat hating”)•Found mostly in fatty tissues, membranes, and other nonpolar biological structures

LipidsDefinitions

Lipid (Greek: lipos, fat): Organic molecule of biological origin that is insoluble in water and soluble in nonpolar solvents (CH2Cl2, CH3CH2OCH2CH3, etc.)

Example: A phospholipid

•Lipid solubility properties due to large nonpolar regions

O

O

O

O

O P

O

O

OCH2CH2NH3

LipidsEight General Categories

Fatty acids Waxes Triacylglycerides

Phospholipids SteroidsProstaglandins

OH

O

CH3(CH2)23CH2 O

O

CH2(CH2)28CH3

O

O

O

R

O

O

R"

R'

O

Lipophilic vitamins

R"

O

O

O

O

O

R'

P

O

O

OCH2CH2NR3COOH

OH

H

HHO

HO

HO

H3C

H H

H

H3C

O

CH3

HO

CH3

CH3

CH3

CH3 CH3 TerpenesProduced mostly by plants

Not discussed in Chem 14C

Fatty AcidsFatty acid: Carboxylic acid with ‘long’ unbranched hydrocarbon chain

Saturated fatty acids

Lauric acid (12 C)

Myristic acid (14 C)

Palmitic acid (16 C)

Stearic acid (18 C)

Arachidic acid (20 C)

OH

O

OH

OOH

OOH

OOH

O

•Most have even number of carbons: Two carbons added at a time during biosynthesis•12-20 carbons most common•Most biologically-important fatty acids have 18 carbons: Stearic, oleic, and linoleic acids•Main biological function: Precursor to other lipids•Categorized by C=C in chain: Saturated (no C=C) or unsaturated (one or more C=C)

Fatty Acids

•Monounsaturated: Contains one C=C•Polyunsaturated: Contains more than one C=C•Cis C=C much more common than trans C=C

OH

O

Linoleic acid (C18)

OH

O

Linolenic acid (C18)

Unsaturated fatty acids

Some important unsaturated fatty acids

Arachidonic acid (C20)

OH

O

C

C C

C

HH

C

C H

C

CH

Cis alkeneCommon in fatty acids

Trans alkeneRare in fatty acids

Oleic acid (C18)

OH

O

remove H2O

Waxes•Most natural waxes are esters derived from a fatty acid and a long-chain alcohol

Example:

•Main biological function of waxes: Water barrier

CH3(CH2)23CH2 O

O

CH2(CH2)28CH3

Myricyl cerotatePresent in beeswax, carnauba wax

Cerotic acidA fatty acid

CH3(CH2)23CH2 OH

O

Myricyl alcoholLong chain alcohol

CH3(CH2)28CH2O H

FeathersWax minimizes wetting

LeavesWax minimizes water evaporation

TriacylglycerolsTriacylglycerol (triacylglyceride): Fatty acid triester of glycerol (glycerin)

•Triacylglycerol = fat if solid at room temperature; oil if liquid

•The most abundant of the natural lipids

•Main biological function: Energy storage

•Hydrolysis (“water breaking”) of animal fats yields soap

- 3 H2O

OH

OH

OH + R'CO2- Na+

+ RCO2- Na+

+ R"CO2- Na+

mixture = soap

OH

OH

+ RCOOH

+ R"COOH

HO + R'COOH

Glycerol Fatty acids

NaOH, H2O

heat

Triacylglycerol

O

O

O

R

O

O

R"

R'

O

Hydrophobic tails dissolve in nonpolar “dirt”

dirt

TriacylglycerolsHow Does Soap Work?

•Hydrophilic CO2- groups attracted to + H-O-H +

•Nonpolar (hydrophobic) hydrocarbon chains avoid water•Nonpolar (lipophilic) hydrocarbon chains attracted to nonpolar “dirt”, other fatty acid chains•Forms micelles (~spherical aggregates); suspends “dirt” in water•Micelles carry dirt away when wash water is removed

Micelle

O O-

OO

-O

O

-

O

O

-

O

O

-

O

O

-

dirt

Hydrophobic tail

Hydrophilic CO2-

Free soapmolecules in H2O

O O-

O

O

-

O

O

-

OO

- OO

-

O

O

-

O

O

-

Hydrophilic head

Hydrophobic tail

TriacylglycerolsSoaps

•Hard water: Contains high levels of Fe3+, Mg2+, Ca2+

•Fatty acid salts of Fe3+, Mg2+, Ca2+ have low water solubility

•Results in precipitates: Dull clothes, “bathtub ring”

•Solution: Synthetic soaps Good water solubility of Fe3+, Mg2+, Ca2+ sulfonates

Avoids dependency on animal fats (expensive; uncertain supply)

S O- Na+

O

O

Sodium 4-dodecylbenzenesulfonateTypical synthetic soap

Soap problems and solutions

Phosphate esterFatty acid esters

PhospholipidsPhospholipid: Glycerol esterified with two fatty acids and one phosphate group

•Phospholipid fatty acids usually palmitic acid, stearic acid, and/or oleic acid•Second most abundant group of natural lipids•Main biological function: Cell membranes (phospholipid bilayer)

Generic phospholipid structure

cell exterior (aqueous)

cytoplasm (aqueous)

hydrophobic tails

hydrophilic heads

•Hydrophobic effect: Hydrophobic tails avoid water

R"

O

O

O

O

O

R'

P

O

O

O X

Mayonaisse – Oil and Vinegar

An example of a phosphatidylcholine, a type of phospholipid in lecithin. •Red - choline and phosphate group•Black – glycerol•Green - unsaturated fatty acid; Blue - saturated fatty acid

• Oil• Vinegar or Lemon Juice• Egg!!!

Lecithin

Lower chain: eight carbons

Upper chain: seven carbons

ProstaglandinsProstaglandin: Molecule having the prostanoic acid skeleton

Prostanoic acid

OH

O

Prostaglandin F2 (PGF2)

COOH

OH

H

HHO

HO

•Nomenclature: Based on stereochemistry, number of OH, C=C, C=O groups•Biological functions: Mostly as regulators and signal molecules

- cause constriction or dilatation in vascular and other smooth muscle cells- regulate aggregation and disaggregation of platelets- sensitize spinal neurons to pain- regulate inflammatory mediation, calcium movement, hormones- control cell growth

Arachidonic acid

O

O

Prostaglandin I2

(PGI2; a prostacyclin)

prostacyclin synthase

OH

PGH-PGEisomerase

COOH

Prostaglandin E2 (PGE2)

PGH-PGF2 reductase

OHHO

Prostaglandin H2 (PGH2)

O

cyclooxygenase-2 (COX-2)and other enyzmes

COOH

OH

COOH

HO

O

OH

COOH

HO

HO

Prostaglandin F2 (PGF2)

COOH

Inhibited by aspirin, Vioxx, etc.

Prostaglandins•Biological origin: Prostaglandin cascade•May occur at wound site, leading to inflammation•In vivo half-life typically 5 minutes or less•Similar structures but wide range of functions

SteroidsSteroid: A molecule having the ring system shown below

Steroid skeleton

A B

C D

Steroid example: CholesterolHO

H3C

H H

H

H3C

•Shape: Core is approximately flat

•Verify and explore with a model

SteroidsCategories and Examples

Sex hormones:

Corticoid hormones:

Testosterone (an androgen)

O

H3C

H3C

H

H H

OH

Estrone (an estrogen)

HO

H3C

H

H H

O

Cortisone•A glucocorticoid hormone•Regulates inflammation•Regulates glucose metabolism

O

H3C

H3C

H

H H

O

CH2OH

OH

O

Aldosterone•A mineralocorticoid hormone•Regulates Na+/K+ balance

O

H3C H

H H

HO

O CH2OH

OH

•Synthesized in the adrenal complex•Regulate metabolic processes

SteroidsCategories and Examples

Bile acids:

Cholic acid•Aid in digestion by emulsifying fats in intestine

Steroids have similar structures but wide range of functions

HO OH

H H

HO

H3C

H

H

CH3

H3C

OH

O

Steroid Biosynthesis•More than sixty steps from acetyl CoA cholesterol

H3C

H3C

HO

H

H

H

many enzymesteps

H3C SCoA

O

Acetyl CoA

H3C

H3C

HO

CH3

HH3C CH3

LanosterolCholesterol•Biological precursor to all other vertebrate steroids

Squaleneepoxidase

Squalene Squalene oxide

O

Squalene oxidocyclase

25 additionalenzymatic steps

Lipophilic VitaminsVitamin: An organic compound, other than fat, protein, or carbohydrate, required for the normal growth and maintenance of animals•Broad range of structures and functions

Vitamin E•Mixture of stereoisomers; -tocopherol most important•Protects against oxidative damage to cells from radicals

O

HO OH

O

OH

OHH

Vitamin C (ascorbic acid)Hydrophilic antioxidant vitamin

Not a lipid

-TocopherolHydrophobic antioxidant vitamin

O

CH3

HO

H3C

CH3

CH3

CH3 CH3

Lipophilic VitaminsVitamin A (retinol)•Essential to vision•Incorporated into rhodopsin (photon-harvesting protein)

An answer to the question “Do we have to memorize all of these structures?”

Expected skills:•Categorize a structure according to its lipid category•Draw generic examples from each lipid category

OH