LIPIDS

LIPIDS - INTRODUCTION• Lipids are non-polar (hydrophobic) compounds, that is

insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform)

• “lipid” is synonymous with “fat”, but also includes phospholipids, sterols, etc.

• Most membrane lipids are amphipathic, having a non-polar end and a polar end.

• Chemical structure: glycerol + fatty acids

LIPIDS

Location in the body Membranes Blood and liver (bound to transport proteins) Adipocytes (adipose tissue)

FUNCTIONS AND PROPERTIES

Concentrated source of energy (9 kcal/gm) Energy reserve: stored as triglycerides in adipose tissues Provide insulation to the body from cold

Maintain body temperature Mechanical insulation

Protects vital organs Electrical insulation

Protects nerves, help conduct electro-chemical impulses (myelin sheath)

Formation of cell membranes Phospholipids, a type of fat necessary for the

synthesis of every cell membrane (also glycoproteins and glycolipids)

FUNCTIONS AND PROPERTIES Synthesis of prostaglandins from fatty acids

Hormone-like compounds that modulates many body processes Immune system, nervous systems, and GI

secretionsRegulatory functions: lower BP, blood clotting,

uterine contractions Help transport fat soluble vitamins Palatability and aroma

Flavor and taste The satiety value – help control appetite

Fullness; fats are digested slower

LIPID CLASSIFICATION Simple: FA’s esterified with glycerol

Fats, Waxes

Complex: same as simple, but with other compounds also attached Phospholipids (+ P) Glycolipids (+ CHO) Lipoproteins (+ fat)

Derived: substances from the above derived by hydrolysis Steroids Prostaglandins

FATTY ACIDS

Contain an even number of carbon atoms Arranged in an unbranched line Have a carboxyl group (-COOH) at one end Have a methyl group (CH3) at the other end

• A 16-C fatty acid:

Non-polar polar

CH3(CH2)14 -COO-

FATTY ACID CHAIN LENGTH

Short chain: 2 to 6 C (volatile fatty acids)

Medium chain: 8 – 12 C Long chain: 14 – 24 C

As chain length increases, melting point increases

Fatty acids synthesized by plants and animals have an even number of carbonsMostly long chain16C to 18C fatty acids are most prevalent

FATTY ACID SATURATION Saturated - no double bonds Unsaturated – contain double bonds

Monounsaturated – one double bond Polyunsaturated - >1 double bond The double bond is a point of unsaturation

As number of double bonds increases, melting point decreases

SATURATED FATS

All the chemical bonds between the carbon are single bonds C-C-C-

No double bonds No space for more H atoms; fully

“saturated” Solid at room temperature

Butter, shortening, lard, coconut oil, palm oil, and fully hydrogenated vegetable oils

Poultry skin, whole milk

MONO-UNSATURATED FATTY ACIDS

Only one double bond Therefore, two H atoms can be added Liquid at room temperature

Olive oil, canola oil, peanut oil Other sources: avocado, almonds, cashews,

pecans and sesame seeds (tahini paste)

POLY-UNSATURATED FATTY ACIDS

Two or more double bonds Include omega-3 and omega-6 fatty

acids (essential fatty acids)Linolenic acid: omega 3 fatty acidLinoleic acid: omega 6 fatty acid

Richest sources of poly-unsaturated fatty acids include:Vegetable oils

Corn, sunflower, safflower, cotton seed oils

FATTY ACIDS COMMONLY FOUND IN LIPIDS

Sat. Fatty Acids Formula Melting Point (oC) Butyric C4H8O2 Liquid Palmitic C16H22O2 63 Stearic C18H36O2 70 Unsat. Fatty Acids Formula Melting Point (oC) Oleic C18H34O2 Liquid Linoleic C18H32O2 Liquid Linolenic C18H30O2 Liquid

Some fatty acids and their common names:14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cis9  oleic acid18:2 cis9,12  linoleic acid18:3 cis9,12,15  linolenic acid 20:4 cis5,8,11,14  arachidonic acid20:5 cis5,8,11,14,17  eicosapentaenoic acid (an omega-3)

FATTY-ACID NOMENCLATURE

Named according to chain length C18

H3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

FATTY-ACID NOMENCLATURE

Named according to the number of double bonds C18:0

H3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

Common name:Stearic acidCommon name:Stearic acid

H3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

FATTY-ACID NOMENCLATURE

Named according to the number of double bonds C18:1

Common name:Oleic acidCommon name:Oleic acid

H3CCH2

CH2

CH2

CH2

CH

CH

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

Named according to the number of double bonds C18:2

FATTY-ACID NOMENCLATURE

Common name:Linoleic acidCommon name:Linoleic acid

H3CCH2

CH

CH

CH2

CH

CH

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

Named according to the number of double bonds C18:3

FATTY-ACID NOMENCLATURE

Common name:Linolenic acidCommon name:Linolenic acid

Named according to the location of the last double bond Omega system (e.g., omega 3, 3) n–system (e.g., n–3)

FATTY-ACID NOMENCLATURE

Named according to the location of the last double bond Omega system (e.g., omega 3, 3) n–system (e.g., n–3)

Count from the methyl end

FATTY-ACID NOMENCLATURE

H3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

FATTY-ACID NOMENCLATURE

H3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

H3CCH2

CH2

CH2

CH2

CH

CH

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

H3CCH2

CH

CH

CH2

CH

CH

CH2

CH

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

Omega 9 or n–9 fatty acid

Omega 6 or n–6 fatty acid

Omega 3 or n–3 fatty acid

FATTY ACID NUMBERING SYSTEMS Delta system: carbon atoms in a fatty acid

are numbered from the carboxyl end Omega system: carbon atoms are numbered

from the methyl end

OMEGA SYSTEM

C-C-C=C-C-C=C-C-C=C-C-C-C-C-C-C-C-COOH

Animals can synthesize a fatty acid with a double bond in the omega 9 position but not at either 3 or 6 positionsOmega-3 and omega-6 fatty acids must be

derived from diet Cold water fish accumulate high levels

of omega 3 fatty acids from their diet

Ω-3 Ω-6 Ω-9

OMEGA SYSTEM AND ESSENTIAL FATTY ACIDS

Linoleic acid is an omega-6 fatty acid Linolenic and arachidonic acids are omega-3

fatty acids Linoleic and linoleic acids are essential fatty

acids Arachidonic acid can be synthesized from them,

so not essential

FATTY-ACID NOMENCLATURE

Named according to location of H’sCis or trans fatty acids

                                                                                                          

            

                                                                                                

                

Cis-9-octadecenoic acid(Oleic acid)

Trans-9-octadecenoic acid(Elaidic acid)

CH C

H2

CH2

CH2

CH2

CH2

CH2

CH2

CH3CCH2

CH2

CH2

CH2

CH2

CH2

CH2

CH O

OH

FATTY-ACID NOMENCLATURE

CH

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CO

OH

H 3C C

H 2

CH 2

CH 2

CH 2

CH 2

CH 2

CH 2

CH

DESIGNATING POSITION OF BONDS

CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Numeric (9,12 – 18:2) ∆ (18:2 ∆ 9,12) n (18:2 n-6) ω (18:2 ω-6) C

O

O 1

23

4

fatty acid with a cis-9 double bond

MELTING POINTS

Affected by chain lengthLonger chain = higher melting temp

Fatty acid: C12:0 C14:0 C16:0 C18:0 C20:0Melting point: 44°C 58°C 63°C 72°C 77°C

CHAIN LENGTH

In most fats with a mixture of fatty acids, the chain length of the majority of fatty acids will determine the “hardness” of the fat<10 carbons = liquidBetween 10 and 20 carbons = ???>20 carbons = solid

Acetic Acid (2 C) Vinegar liquid

Stearic Acid (18 C) Beef Tallow Solid

Arachidic Acid (20 C)

Butter Solid

MELTING POINTS

Affected by number of double bondsMore saturated = higher melting temp

Fatty acid: C18:0 C18:1 C18:2 C18:3Melting point: 72°C 16°C –5°C –11°C

ESSENTIAL FATTY ACIDS

Must be in dietTissues can not synthesizeLinoleic acid (18:2)

Omega-6-FALinolenic acid (18:3)

Omega-3-FAArachidonic (20:4)

Not in plants! Can be synthesized from C18:2 (except in cat)

STURCTURE OF ESSENTIAL FA’S

FUNCTIONS OF ESSENTIAL FATTY ACIDS A component of the phospholipids in cell

membranes Precursor for prostaglandins: arachidonic acid Important metabolic regulator

Contraction of smooth muscle Aggregation of platelets

ESSENTIAL FATTY ACIDS

Deficiency of essential fatty acid intakes: Growth retardation Problems with reproduction Skin lesions Kidney and liver disorders

TRIGLYCERIDES – SIMPLE LIPIDS

Most common structure in dietary lipids Composed of one glycerol molecule and three

fatty acids connected by an ester bond (bond between an alcohol and and organic acid) Fatty acids may be same or mixed

Glycerol

Fatty Acid

Fatty Acid

Fatty Acid

MOST COMMON FATTY ACIDS IN DI- AND TRIGLYCERIDES

Fatty acid Carbon:Double bonds Double bonds

Myristic 14:0

Palmitic 16:0

Palmitoleic 16:1 Cis-9

Stearic 18:0

Oleic 18:1 Cis-9

Linoleic 18:2 Cis-9,12

Linolenic 18:3 Cis-9,12,15

Arachidonic 20:4 Cis-5,8,11,14

Eicosapentaenoic 20:5 Cis-5,8,11,14,17

Docosahexaenoic 22:6 Cis-4,7,10,13,16,19

CH3(CH2)nCOOH

COMPLEX LIPIDS - PHOSPHOLIPIDS

Two primary types: Glycerophosphatides

Core structure is glycerol Part of cell membranes, chylomicrons, lipoproteins

Sphingophosphatides Core structure is sphingosine Part of sphingomyelin

PHOSPHOLIPIDS

Phospholipid sources: Liver, egg yolk, Soybeans, wheat germ Peanuts

GLYCEROPHOSPHOLIPIDS

C OHH

CH2OH

CH2OH

glycerol

Glycerophospholipids (phosphoglycerides), are common constituents of cellular membranes.They have a glycerol backbone.Hydroxyls at C1 & C2 are esterified to fatty acids.

An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H2O.

Formation of an ester:

O O

R'OH + HO-C-R" R'-O-C-R'' + H2O

PHOSPHATIDATE

In phosphatidate: fatty acids are esterified to hydroxyls on C1

& C2 the C3 hydroxyl is esterified to Pi.

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

phosphatidate

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

X

glycerophospholipid

In most glycerophospholipids (phosphoglycerides), Pi is in turn esterified to OH of a polar head group (X): e.g., serine, choline, ethanolamine, glycerol, or inositol.

The 2 fatty acids tend to be non-identical. They may differ in length and/or the presence/absence of double bonds.

Phosphatidylinositol, with inositol as polar head group, is one glycerophospholipid.

In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling.

O P

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

OH

H

OH

H

H

OHH

OH

H

O

H OH

phosphatidyl- inositol

Phosphatidylcholine,(Lecithin) with choline as polar head group, is another glycerophospholipid.

It is a common membrane lipid.

O P O

O

O

H 2 C

C H

H 2 C

OCR 1

O O C

O

R 2

C H 2 C H 2 N C H 3

C H 3

C H 3

+

p h o sp h a tid ylc h o lin e

Each glycerophospholipidincludes a polar region:

glycerol, carbonyl O of fatty acids, Pi, & the polar head group (X)

non-polar hydrocarbon tails of fatty acids (R1, R2).

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

X

glycerophospholipid

H2CHC

OH

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

sphingosine

Sphingosine may be reversibly phosphorylated to produce the signal molecule sphingosine-1-phosphate. Other derivatives of sphingosine are commonly found as constituents of biological membranes.

Sphingolipids are derivatives of the lipid sphingosine, which has a long hydrocarbon tail, and a polar domain that includes an amino group.

sphingosine-1-P

H2CHC

O

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

P O

O

O

H2CHC

OH

CH

NH CH

C

CH2

CH3

H

OH

( )12

C

R

O

ceramide

H2CHC

OH

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

sphingosine

In the more complex sphingolipids, a polar “head group" is esterified to the terminal hydroxyl of the sphingosine moiety of the ceramide. 

The amino group of sphingosine can form an amide bond with a fatty acid carboxyl, to yield a ceramide.

Sphingomyelin, with a phosphocholine head group, is similar in size and shape to the glycerophospholipid phosphatidyl choline.

Sphingomyelin has a phosphocholine or phosphethanolamine head group.

Sphingomyelins are common constituent of plasma membranes

H2CHC

O

CH

NH CH

C

CH2

CH3

H

OH

( )12

C

R

O

PO O

O

H2C

H2CN+

CH3

H3C

CH3

Sphingomyelin

phosphocholine

sphingosine

fatty acid

GLYCOLIPIDS

A cerebroside is a sphingolipid (ceramide) with a monosaccharide such as glucose or galactose as polar head group.

A ganglioside is a ceramide with a polar

head group that is a complex oligosaccharide, including the acidic sugar derivative sialic acid.Cerebrosides and gangliosides, collectively called glycosphingolipids, are commonly found in the outer leaflet of the plasma membrane bilayer, with their sugar chains extending out from the cell surface.

cerebroside with -galactose head group

H2CHC CH

NH CH

C

CH2

CH3

OH

C

R

O

OH O

H H

H

OHH

OH

CH2OH

HO

H

( )12

LIPOPROTEINS

Cholesterol is largely hydrophobic.

But it has one polar group, a hydroxyl, making it amphipathic.

C holestero lH O

Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail.

cholesterol PDB 1N83

Cholesterolin membrane

Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase & its hydrophobic ring system adjacent to fatty acid chains of phospholipids.

The OH group of cholesterol forms hydrogen bonds with polar phospholipid head groups.

C holestero lH O

Depending on the lipid, possible molecular arrangements:

Various micelle structures. E.g., a spherical micelle is a stable configuration for amphipathic lipids with a conical shape, such as fatty acids.

A bilayer. This is the most stable configuration for amphipathic lipids with a cylindrical shape, such as phospholipids.

Bilayer Spherical Micelle

Amphipathic lipids in association with water form complexes in which polar regions are in contact with water and hydrophobic regions away from water.

liquid crystal crystal

In the liquid crystal state, hydrocarbon chains of phospholipids are disordered and in constant motion. At lower temperature, a membrane containing a single phospholipid type undergoes transition to a crystalline state in which fatty acid tails are fully extended, packing is highly ordered, & van der Waals interactions between adjacent chains are maximal. Kinks in fatty acid chains, due to cis double bonds, interfere with packing in the crystalline state, and lower the phase transition temperature.

Membrane fluidity:

The interior of a lipid bilayer is normally highly fluid.

But the presence of cholesterol in a phospholipid membrane interferes with close packing of fatty acid tails in the crystalline state, and thus inhibits transition to the crystal state.

Phospholipid membranes with a high concentration of cholesterol have a fluidity intermediate between the liquid crystal and crystal states.

Cholesterolin membrane

Interaction with the relatively rigid cholesterol decreases the mobility of hydrocarbon tails of phospholipids.

Two strategies by which phase changes of membrane lipids are avoided: Cholesterol is abundant in membranes, such as plasma

membranes, that include many lipids with long-chain saturated fatty acids.

In the absence of cholesterol, such membranes would crystallize at physiological temperatures.

The inner mitochondrial membrane lacks cholesterol, but includes many phospholipids whose fatty acids have one or more double bonds, which lower the melting point to below physiological temperature.

ERGOSTEROL

Occurs in plant Found as structural constituents of membrane in

yeast and fungi. Important precursor of vitamin D