CH 25

LIPIDS

Substances extracted from cells and tissues by nonpolar organic solvents

Classes of LipidsComplex Lipids - easily degraded to smaller components (fatty acids often) EX.s Fats, Oils, Waxes Simple Lipids - not easily degraded to smaller components EX.s Steroids, Prostaglandins, Terpenes

I. WAXES
Esters of long straight chain carboxylic (fatty) acids with long straight chain alcohols
O CH3(CH2)n C O a wax (CH2)mCH3 Typically: n = 14 to 34 (even) m = 23 to 35 (odd)

- serve as protective coatings, structural materials & food sources for many plants & animals

EX.s
O CH3(CH2)14 C O (CH2)29CH3 beeswax O CH3(CH2)30 C O (CH2)33CH3 carnauba wax O CH3(CH2)14 C O (CH2)15CH3 spermaceti wax

- natural waxes are not the same as paraffin waxes (they are high molecular weight alkanes)

II. TRIGLYCERIDES
Glyceride = ester of glycerol (propane-1,2,3-triol) - most common glyceride = triester (triglyceride or triacylglycerol) - also known as a fat or oil
O CH2 O C R O CH O C R' O From CH2 OH CH OH CH2 OH Glycerol & O HO C R O HO C R' O HO C R'' Fatty Acids

CH2 O C R'' Triglyceride Fat or Oil

R, R', R'' can be the same (simple triglyceride) or not the same (mixed triglyceride)

Fatty Acids, FAs

- long, straight-chain (no branches) carboxylic acids with even numbers of carbons

Saturated Fatty Acids, satd FAs

CH3 (CH2)n sat'd FA COOH Typically: n = 10 to 18 (even) total # C's = 12 to 20 (even)

- satd FA straight chains align well & pack closely in the solid state:
COOH COOH

- thus, satd FAs have high MPs and are solids at room temperature, RT

- Table 25-1; p.1202

Unsaturated Fatty Acids, unsatd FAs

CH3 (CH2)n (CH CH)m (CH2)n COOH Typically: n = 2 to 8 (even) m = 1 to 4 (cis , mostly) c total # C's = 18 to 20 (even) C H C H

unsat'd FA

cis double bonds -- conjugated or isolated

- unsatd FA cis double bonds create kinks in chains - do not align well & cannot pack closely in the solid state:

COOH COOH

- thus, unsatd FAs have low MPs and are liquids at room temperature, RT - as the # C=C s 8 ; MP 9 Table 25-1; p.1202

Fats - triglycerides which are solids @ RT - contain mostly satd FA esters (close packing Y higher MPs)
O CH2 O C O CH O C O C (CH2)n CH3 (CH2)n CH3 (CH2)n CH3 or O O O O O O

Table 25-2; p.1203

CH2 O

Fat

EX.s Lard, Tallow, Butter, Nutmeg, Coconut Oil (misnomer) Sources Y plants and warm-blooded animals

Oils - triglycerides which are liquids @ RT - contain mostly unsatd FA esters (poor packing Y lower MPs) Table 25-2; p.1203

O CH2 O C O CH O C O C (CH2)n (CH CH)m (CH2)n CH3 (CH2)n (CH CH)m (CH2)n CH3 (CH2)n (CH CH)m (CH2)n CH3 Oil or O O

O O O

CH2 O

EX.s Cod Liver Oil, Herring Oil, Olive Oil, Peanut Oil Sources Y plants and cold-blooded animals

Hardening of Oils - to replace lard, vegetable oils are converted to solids via catalytic hydrogenation (reduction) - Partially Hydrogenated Vegetable Oils result, such as Margarine & Shortening (Crisco)
H2 Corn Oil C H C H Ni,

EX.

Margarine H H C C H H (solid)

(liquid)

Advantages: - improved consistency & texture - less potential for allylic oxidation, which causes rancidity when polyunsaturated vegetable oils are heated during the cooking process Disadvantages: - saturated fats are less healthy than unsaturated fats - heating on the catalyst surface during partial hydrogenation causes the remaining double bonds to migrate and isomerize from cis to (more stable) trans, producing unhealthy trans fats

III. SOAPS & DETERGENTS

Soap = the sodium or potassium carboxylate salt of a fatty acid - prepared by saponification of a triglyceride (basic or alkaline hydrolysis of an ester)
O CH2 O C R O CH O C R' O CH2 O C R'' Triglyceride Fat or Oil Typically: R, R', R'' = or = ; sat'd or unsat'd FA 's All R 's = n-C11 to n-C17 (odd) Soap's total # C 's = 12 to 18 (even) + 3 NaOH CH2 OH CH OH CH2 OH Glycerol + R COO Na

H2 O

R' COO Na R'' COO Na Soaps

Micelle Formation - property responsible for cleaning action of soap - soap molecule has a structurally dual nature:
O O Na nonpolar tail hydrophobic polar head hydrophilic or soap

- in water, soap molecules self-assemble into spherical structures called micelles:

- hydrophilic heads outside & hydrophobic tails inside - grease, oil, dirt dissolves in hydrophobic region (inside) - water surrounds the hydrophilic region (outside) - grease (dirt) is removed (floats away) from cloth, skin,.... - an emulsion results (two insoluble phases mix)

- in addition to being an emulsifier, soap can also act as a: Surfactant or Wetting Agent - micelles are like-charged, thus, they repel each other, lowering the surface tension of water - this improves waters efficiency in soaking into the surface of the object being cleaned

Problems - soaps usefulness is limited by three major drawbacks:

1) Alkalinity - being the conjugate base (CB) of a weak acid (WA), soap hydrolyzes water:
R COO Na + H 2O hydrolyzes R COOH + Na OH WA basic soln'

CB of WA

- most soap solutions, pH . 9 ; the alkalinity harms fabrics & dries out skin (pH . 5.5)

2) Precipitation in Acidic Solutions - soap becomes insoluble in water with pH < 7 & loses its cleaning potential
R COO Na + H R COOH + Na

soluble, cleans

insoluble, no cleaning (soap scum)

3) Precipitation in Hard Water - hard water ions form insoluble salts with soap, again eliminating its cleaning properties
R COO Na + Mn hard water ion (R COO )n Mn + Na

soluble, cleans

Mn = Mg2, Ca2, Fe3

insoluble ppt, no cleaning (bathtub ring)

Synthetic Detergents
- to remedy problems associated with soap, syndets have been developed - they are fatty acid derivatives with non-carboxylate polar head functional groups

nonpolar tail hydrophobic

polar head hydrophilic

not

COO

- like soap, syndets form micelles & are therefore cleaners, emulsifiers & surfactants - but syndets do not produce alkaline solutions or form precipitates in acidic or hard water - there are three classes of syndets, based on their hydrophilic polar head functional groups

A. Anionic Syndets
CH3 (CH2)n OSO3 Na sodium alkyl sulfates n = 11 mostly CH3 (CH2)n SO3 Na

sodium alkylbenzene sulfonates n = 9 to 13 (odd)

B. Cationic Syndets
CH3 (CH2)n NR3 Cl quaternary ammonium chlorides n = 15 or 17 R = CH3 mostly

C. Nonionic Syndets

CH3 (CH2)n

(OCH2CH2)m

OH

n = 7 to 11 (odd) m = 5 to 10

alkyl phenol ethoxylates

IV.

PHOSPHOLIPIDS

- compounds related to triglycerides which contain phosphoric acid ester groups:

O HO P OH phophoric acid OH + 2 ROH - 2 H 2O O RO P OH phosphodiester OR -H O RO P O ionized @ physiological pH OR

Phosphoglycerides
- the most common class of phospholipid (other classes have non-glycerol alcohol portions) - phosphoglycerides are constructed from a glycerol with two FA esters & one phosphate ester.
O CH3 (CH2)n C O CH2 O CH3 (CH2)x (CH CH)m (CH2)x C O CH O O CH2CH2 NR3 O

CH2 O P a phosphoglyceride Typically: n = 12 to 16 m = 1 or 2 x = 4 or 7 R Group H CH3

Phosphoglyceride Class Cephalins Lecithins

- phospholipids have an amphiphilic structure similar to soaps & detergents

O O O O O P O O polar head hydrophilic or phospholipid NR3

nonpolar tails hydrophobic

Phospholipid Bilayer - phospholipids self-assemble in solution to form micelle-like aggregates

Cell Membranes - use lipid bilayers for their primary construct - have membrane proteins embedded inside, outside or across the bilayer - control the flow of ions & molecules in & out of cells - cis double bonds in the unsatd FA residues keep the membranes fluid & flexible

V. PROSTAGLANDINS
- fatty acid-derived compounds usually containing twenty carbons (C20) - produced along with other similar classes of compounds from a single precursor: - Eicosa-(Z5,Z8,Z11,Z14)-tetraenoic Acid, commonly known as Arachidonic Acid - an unsatd C20 FA (with four cis C=C) - hence, prostaglandins & their related compounds are referred to as Eicosanoids - they are biosynthesized as follows:

Arachidonic Acid Cascade:

Phospholipids Cell Membranes

COOH

Arachidonic Acid

Analgesics inhibit here O O

H COOH H Leukotrienes

OOH

Prostaglandins Thromboxanes Prostacyclins

EX.
O
9 10 11 8 12 7 6 5 3 16 15 18 17 19 4 2

H H
13 14

COOH
20

PG = Prostaglandin E= keto @ C-9 2=2xC C

H OH

H PGE2

OH

Biological Activity of Eicosanoids - prostaglandins & their related compounds initiate & regulate most physiologic functions: - Systems affected: nervous, smooth muscle, blood, reproductive,..... - Functions regulated: blood pressure, clotting & thinning, also, digestion, labor, breathing,.... - Responses initiated: pain, inflammation, fever,..... - they are often complementary in their activities Y biological off/on switches EX. Thromboxanes - platelet aggregators (blood clotting) Prostacyclins - inhibit platelet aggregators (blood thinning)

- they produce profound effects while employing only minute quantities - eicosanoids, their inhibitors and their synthetic derivatives are widely used as medicinals

VI. TERPENES
Essential Oils - fragrant, flavorful extracts from many plant sources used as perfumes, medicinals,.... - composed of compounds whose carbon skeletons contain multiples of five-carbon units EX. C10, C15, C20, C30, C40, .......

Isoprene Units - the five-carbon units from which terpenes are constructed:

tail an isoprene unit

head

named after: isoprene (2-methyl-1,3-butadiene)

- in nature, isoprene units are biosynthesized from fatty acids:

O FA fatty acid H 3C C H 2C CH3 C CH2 CH2 OPP join Terpene head-tail

acetate unit

isopentenyl pyrophosphate (an isoprene unit)

Terpene Y two or more isoprene units joined in a head-to-tail fashion

Classes of Terpenes

# Cs 10 15 20 30 40

# Isoprene Units 2 3 4 6 8

Class Name Monoterpene Sesquiterpene Diterpene Triterpene Tetraterpene

EX s
OH Geraniol (a C10 Monoterpene) Retinal (a C20 Diterpene) head to head O

Squalene (a C30 Triterpene)

head to head

-Carotene
(a C40 tetraterpene)

VII. STEROIDS
- polycyclic compounds derived from terpenes

General Steroid Structure

R
13 14 17

12 11 1 2

R
16

C
10 5

D
15

A O
3 4

B
6

or

O H

A H

C B H

8 7

Typically: - angular methyl groups @ C-10 & C-13 - trans ring junctions @ C-5 & C-14 - functional group side chain @ C-17 - oxygen functional group @ C-3

Steroid Biosynthesis
O FA fatty acid acetate unit OPP isopentenyl pyrophosphate (one isoprene unit) OH farnesol (a C15 sesquiterpene, 3 isoprene units)

Squalene (a C30 Triterpene, 6 isoprene units)

HO Cholesterol (a C27 Steroid) Vitamin D Adrenocortical Hormones Bile Salts Sex Hormones

HO Lanosterol (a C30 Steroid)

Cholesterol Functions: - most abundant steroid - biosynthetic precursor to all other functional steroids - forms esters @ C-3 OH with unsatd FAs
HO Cholesterol

- cholesteryl esters keep cell membranes fluid - high levels of serum cholesterol lead to: - gallstones, high LDL levels & arterial plaques

Bile Salts
O OH G G OH NH CH2CH2 SO3H HO OH NH CH2 COOH Bile Salt Cholic Acid Taurocholic Acid Glycholic Acid

Function: - biodetergents Y form micelles in digestive tract - emulsify fats & oils, aid in absorption of lipid compounds across intestinal membranes

Sex Hormones
- there are two classes of steroid hormones which differentiate gender: 1) Estrogens - the class of female hormones, EX s
O OH

&

O Progesterone

HO Estradiol

Functions: - responsible for secondary female sex characteristics -female genitalia & breast development, lack of facial hair,....... - regulate the menstrual cycle - initiate & maintain pregnancy by preventing further ovulation (progestins) - derivatives of progestins are used as contraceptives

EX.

OH a synthetic contraceptive active ingredient in a "birth control pill" O Norethindrone (Norlutin)

2) Androgens - the class of male hormones,

EX s
O

OH

HO Androsterone

O Testosterone

Functions: - responsible for secondary male sex characteristics - male genitalia & development of testes, facial hair, male musculature,...... - derivatives of androgens are used as muscle-building anabolic steroids

EX.
O O an anabolic steroid stimulates muscle growth enhances athletic performance O Nandrolone decanoate

Sex Hormone Biosynthesis

- alternating pathway of estrogens,
O

& & androgens, %

OH OH

O Progesterone

O Testosterone

HO Estradiol

&
Biological Specificity

&

- minuscule difference in structure results in enormous difference in function - compounds so similar they are made from one another, yet physiologic effects are disparate

Adrenocortical Steroids
- adrenocorticoid hormones are synthesized in the cortex of the adrenal gland EX s
O OH G OH G OH OH O O Adrenocorticoid Cortisol Hydrocortisone Cortisone

Functions: - regulate the inflammatory response by controlling glucose synthesis & the flow of ions & water - adrenocortical steroids & their synthetic derivatives are used as antiinflammatory drugs