Chemistry 121(01) Winter 2010-11 Introduction to Organic Chemistry and Biochemistry Instructor Dr. Upali Siriwardane (Ph.D. Ohio State) E-mail: [email protected] Office: 311 Carson Taylor Hall ; Phone: 318-257-4941; Office Hours: MWF 8:00 am - 10:00 am; TT 9:00 – 10:00 am & 1:00-2:00 pm.

Chapter 19. Lipids Sections

December 17, 2010 Test 1 (Chapters 12-13) January 19, 2011 Test 2 (Chapters 14,15 & 16) February 7, 2011 Test 3(Chapters 17, 18 & 19) February 23, 2011 Test 4 (Chapters 20, 21 & 22) February 24, 2011 Comprehensive Make Up Exam:

Chemistry 121 Winter 2011 LA Tech

19-1

19-2

Lipids

Chapter 19 19.1 Structure and Classification of Lipids 19.2 Fatty Acids: Lipid Building Blocks 19.3 Physical Properties of Fatty Acids 19.4 Energy-Storage Lipids: Triacylglycerols 19.5 Dietary Considerations and Triacylglycerols 19.6 Chemical Reactions of Triacylglycerols 19.7 Membrane Lipids: Phospholipids 19.8 Membrane Lipids: Sphingoglycolipids 19.9 Membrane Lipids: Cholesterol 19.10 Cell Membranes 19.11 Emulsification Lipids: Bile Acids 19.12 Messenger Lipids: Steroid Hormones 19.13 Messenger Lipids: Eicosanoids 19.14 Protective-Coating Lipids: Biological Waxes Chemistry at a Glance: Types of Lipids and How They Function Chemical Connections: The Fat Content of Tree Nuts and Peanuts; Artificial Fat Substitutes; The Cleansing Action of Soap; Trans Fatty Acids and Blood Cholesterol Levels; Steroid Drugs in Sports; The Mode of Action for Anti-Inflammatory Drugs Chemistry 121 Winter 2011 LA Tech

Chemistry 121 Winter 2011 LA Tech

19-3

A heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties • insoluble in water • soluble in aprotic organic solvents including diethyl ether, dichloromethane, and acetone

Lipids include • • • • • •

Waxes triglycerides phospholipids Prostaglandins cholesterol, steroid hormones, and bile acids fat-soluble vitamins

Chemistry 121 Winter 2011 LA Tech

19-4

1

Structure and Classification of Lipids Lipids that are ester or amides of fatty acids:

Wax

Waxes – are carboxylic acid esters where both are carboxylic acid esters where both R groups are long straight hydrocarbon chain. R groups are long straight hydrocarbon chain. Performs external protective functions. Performs external protective functions. Triglycerides– are carboxylic acid are carboxylic acid triesters of Glycerols . They are a major source of biochemical energy. Glycolipids – amides derived from sphingosine, contain polar carbohydrate groups. On the cell surface, they connect with intracellular messengers. Glycerophopholipids – triesters of glycerols that contain charged phosphate diesters. They help to control the flow of molecules into and out of cells. Sphingomyelins – amides derived from an amino alcohol, also contain charged amino alcohol, phosphate diester groups. They are essential to the structure of cell membranes.

esters are fatty acids esterified to long-chain saturated or monoenoic (one double bond) alcohols. They are carboxylic acid esters where both are carboxylic acid esters where both R groups are long straight hydrocarbon chain. R groups are long straight hydrocarbon chain. They performs external protective functions. Performs external protective functions.

O

Beeswax

CH3(CH2)24

O

(CH2)29CH3

Spermaciti: sperm whale wax

O CH3(CH2)14

Lipids that are not esters or amides:

O

(CH2)15CH3

Steroids – They performs various functions They performs various functions such as hormones and contributes to the structure of cell membranes. Eicosanoids – They are carboxylic acids that are a special type of intracellular chemical Messengers. Chemistry 121 Winter 2011 LA Tech

19-5

Chemistry 121 Winter 2011 LA Tech

19-6

Triglycerides

H2C O CH2OH CHOH

Spermaceti source

O

RCOOH HC O

CH2OH Glycerol

O C O H2 O Saturated Fat or Oil

Carnauba wax source

Bee’s wax Chemistry 121 Winter 2011 LA Tech

19-7

Chemistry 121 Winter 2011 LA Tech

19-8

2

Properties of Fats and Oils

Physical properties of Triglycerides

Oils: A mixture of triglycerides that is liquid because it contains a high proportions of unsaturated fatty acids. Fats : A mixture of triglycerides that is solid because it contains a high proportions of saturated fatty acids.

Depends on their fatty acid components

Chemistry 121 Winter 2011 LA Tech

19-9

Triglycerides

Chemistry 121 Winter 2011 LA Tech

19-10

Reduction of Triglycerides

The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape • hydrocarbon chains of saturated fatty acids can lie parallel with strong dispersion forces between their chains; they pack into well-ordered, compact crystalline forms and melt above room temperature • because of the cis configuration of the double bonds in unsaturated fatty acids, their hydrocarbon chains have a less ordered structure and dispersion forces between them are weaker; these triglycerides have melting points below room temperature

Chemistry 121 Winter 2011 LA Tech

• melting point increases as the number of carbons in their hydrocarbon chains increases and as the number of double bonds decreases • triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oils • triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fats

19-11

• the process of converting fats to oils is called hardening and involves catalytic reduction of some or all of an oil’s carbon-carbon double bonds • in practice, the process is controlled to produce a fat of a desired consistency • the resulting fats are sold for cooking (Crisco, Spry, and others) • margarine and other butter substitutes are produced by partial hydrogenation of polyunsaturated oils derived from corn, peanuts, and soybeans • because catalytic hydrogenation is to some degree reversible, hardening results in the isomerization of some cis-fatty acids to trans-fatty acids; trans fatty acids are to be avoided as much as possible

Chemistry 121 Winter 2011 LA Tech

19-12

3

Triglycerides

Soaps and Detergents

An ester of glycerol with three fatty acids

Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap)

O O CH2 OCR R'COCH O

1 . NaOH, H2 O

CH2 OCR'' 2 . HCl, H2 O

A triglyceride

CH2 OH HOCH CH2 OH

RCOOH +

R'COOH

R''COOH 1,2,3-Propanetriol Fatty acid s (Glycerol, glycerin )

Chemistry 121 Winter 2011 LA Tech

19-13

Soaps and Detergents

CH2 OCR A triglyceride

CH2 OH CHOH

+

O 3RCO- Na+

CH2 OH Sodium soaps 1,2,3-Propanetriol (Glycerol; glycerin)

Chemistry 121 Winter 2011 LA Tech

19-14

Soaps and Detergents

Soaps clean by acting as emulsifying agents • the long hydrophobic hydrocarbon chains of soaps are insoluble in water and tend to cluster in such a way as to minimize their contact with water • the polar hydrophilic carboxylate groups tend to remain in contact with the surrounding water molecules • driven by these two forces, soap molecules spontaneously cluster into micelles • Micelle: a spherical arrangement of organic molecules in water clustered so that their hydrophobic parts are buried inside the sphere and their hydrophilic parts are on the surface of the sphere and in contact with water Chemistry 121 Winter 2011 LA Tech

O O CH2 OCR sap on ification RCOCH O + 3 NaOH

19-15

• when soap is mixed with water-insoluble grease, oil, and fat stains, the nonpolar parts of the soap micelles “dissolve” nonpolar dirt molecules and they are carried away in the polar wash water

Chemistry 121 Winter 2011 LA Tech

19-16

4

Soaps

Synthetic Detergents

Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard water)

The design criteria for a good detergent are

-

+

2 CH3 (CH2 ) 1 4 COO Na

+

Ca

2+

A sodiu m s oap (soluble in w ater as micelles) [CH3 (CH2 ) 1 4 COO- ] 2 Ca2 + + 2 Na+ Calcium salt of a fatty acid (insolub le in w ater)

• a long hydrocarbon tail of 12 to 20 carbons • a polar head group that does not form insoluble salts with Ca(II), Mg(II), or Fe(III) ions • the most widely used synthetic detergents are the linear alkylbenzenesulfonates (LAS)

CH3 (CH2 ) 1 0 CH2

1 . H2 SO4 2 . NaOH

D odecylben zene

CH3 (CH2 ) 1 0 CH2

-

SO3 Na

+

S od ium 4-dodecylb enzenes ulfon ate (an an ion ic detergent)

• also added to detergent preparations are foam stabilizers, bleaches, and optical brighteners Chemistry 121 Winter 2011 LA Tech

19-17

Fatty Acids

19-18

Fatty Acids The most abundant fatty acids

A long, unbranched chain carboxylic acid • nearly all have an even number of carbon atoms, most between 12 and 20, in an unbranched chain • the three most abundant are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1) • in most unsaturated fatty acids, the cis isomer predominates; the trans isomer is rare • unsaturated fatty acids have lower melting points than their saturated counterparts; the greater the degree of unsaturation, the lower the melting point

Chemistry 121 Winter 2011 LA Tech

Chemistry 121 Winter 2011 LA Tech

19-19

Carb on Atoms / D ouble Bond s Stru cture Saturated Fatty Acids 12:0 CH3 ( CH2 ) 1 0 COOH

Common Name

mp (°C)

lau ric acid

44

CH3 ( CH2 ) 1 4 COOH

myris tic acid palmitic acid

58 63

18:0

CH3 ( CH2 ) 1 6 COOH

stearic acid

70

20:0

CH3 ( CH2 ) 1 8 COOH

arach idic acid

77

palmitoleic acid oleic acid

16

14:0 16:0

CH3 ( CH2 ) 1 2 COOH

Unsatu rated Fatty Acid s 16:1 CH3 ( CH2 ) 5 CH=CH(CH2 ) 7 COOH 18:1 CH3 ( CH2 ) 7 CH=CH(CH2 ) 7 COOH 18:2

CH3 ( CH2 ) 4 (CH=CHCH2 ) 2 ( CH2 ) 6 COOH lin oleic acid

18:3

CH3 CH2 (CH=CHCH2 ) 3 ( CH2 ) 6 COOH

20:4

CH3 ( CH2 ) 4 (CH=CHCH2 ) 4 ( CH2 ) 2 COOH arach idonic acid

Chemistry 121 Winter 2011 LA Tech

lin olen ic acid

1 -5 -11 -49 19-20

5

Saturated/Unsturated fatty acids

Saturated Fatty Acids

Chemistry 121 Winter 2011 LA Tech

19-21

19-22

Saturated/Unsturated fatty acids

Unsaturated Fatty Aicds

Chemistry 121 Winter 2011 LA Tech

Chemistry 121 Winter 2011 LA Tech

19-23

Chemistry 121 Winter 2011 LA Tech

19-24

6

Saturated/Unstaureated Mixtures

Fatty Acids the greater the degree of unsaturation the lower the melting point COOH Stearic acid (18:0) (mp 70°C) COOH Oleic acid (18;1) (mp 16°C) COOH Linoleic acid (18:2) (mp-5°C) COOH Lin olen ic acid (18:3) (mp -11°C)

Chemistry 121 Winter 2011 LA Tech

19-25

Unsaturated triglyceride

Chemistry 121 Winter 2011 LA Tech

19-26

What are "Omega" series fatty acids? Scientists differentiate fatty acids by the characteristics of their molecules. The two principal essential fatty acids are Omega-6 (n-6) series and the Omega-3(n-3) series. The number indicates the position of the first double carbon bond when counting from a specified end of the molecule.

Chemistry 121 Winter 2011 LA Tech

19-27

Chemistry 121 Winter 2011 LA Tech

19-28

7

Essential Fatty Acids

Phospholipids

Fatty acids that cannot be produced by the body and are necessary for proper metabolism. The OMEGA 6 and OMEGA 3 fatty acids are referred to as Essential Fatty Acids (EFA).

Chemistry 121 Winter 2011 LA Tech

19-29

Phospholipids

Phospholipids are the second most abundant group of naturally occurring lipids • they are found almost exclusively in plant and animal membranes, which typically consist of 40% to 50% phospholipids and 50% to 60% proteins • the most abundant phospholipids are derived from phosphatidic acid, a molecule in which glycerol is esterified with two fatty acids and one phosphoric acid • further esterification with a low-molecular weight alcohol gives a phospholipid • the three most abundant fatty acids in phosphatidic acids are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1) Chemistry 121 Winter 2011 LA Tech

19-30

Examples of glycerophospholipids

Phosphate(PO4 )-containing molecules with structures related to the triglycerides are aclled Glycerophopholipids E.g. Phosphatidycholine (lecithin)

Name

Phosphatidyl choline (lecithin)

Phosphatidyl ethanolamine (cephalin)

Chemistry 121 Winter 2011 LA Tech

19-31

Chemistry 121 Winter 2011 LA Tech

19-32

8

Phospholipids

Phospholipids

A phosphatidate and a phospholipid O

nonp olar hydrocarbon tails

A p hosph atidate

O CH2 O CH O CH2 O-P-OO O O

A p hosph olip id

polar head group s

O CH2 O CH O CH2 -O-P-OCH2 CH2 N(CH3 ) 3 O O

Chemistry 121 Winter 2011 LA Tech

19-33

Chemistry 121 Winter 2011 LA Tech

19-34

Phospholipids

Phosphatidycholine (lecithin)

• low-molecular weight alcohols in phospholipids N ame and Fo rmul a

N ame of Pho spho li pid

ethano lami ne HOCH2 CH2 NH2

cho li ne

pho sphatidy leth ano lami ne (ceph al in)

+

HOCH2 CH2 N(CH3 ) 3

seri ne

pho sphatidy lcho li ne (lecithin)

-

HOCH2 CHCOO NH3

i no sito l HO

OH HO

HO Chemistry 121 Winter 2011 LA Tech

19-35

ph osphatidy lseri ne

+

Chemistry 121 Winter 2011 LA Tech

OH phosp hatid yl ino sitol OH 19-36

9

Lipid Bilayer When placed in aqueous solution, phospholipids spontaneously form a lipid bilayer • polar head groups lie on the surface, giving the bilayer an ionic coating • nonpolar fatty acid hydrocarbon chains lie buried within the bilayer

This self-assembly is driven by two noncovalent forces • hydrophobic effects, which result when nonpolar hydrocarbon chains cluster to exclude water molecules • electrostatic interactions, which result when polar head groups interact with water and other polar molecules in the aqueous environment Chemistry 121 Winter 2011 LA Tech

19-37

Biological Membranes

Plasma membrane Planar lipid bilayers Biological membranes are bilipid layers . In a real cell the membrane phospholipids create a spherical three dimensional lipid bilayer shell around the cell. However, they are often represented two-dimensionally as:

Passive tranport Active transport

Chemistry 121 Winter 2011 LA Tech

19-38

Fluid-Mosaic Model

Fluid mosaic model: a biological membrane consists of a phospholipid bilayer with proteins, carbohydrates, and other lipids embedded on the surface and in the bilayer • fluid signifies that the protein components of membranes “float” in the bilayer and can move freely along the plane of the membrane • mosaic signifies that the various components of the membrane exist side by side, as discrete units rather than combining to form new molecules and ions

Chemistry 121 Winter 2011 LA Tech

19-39

Chemistry 121 Winter 2011 LA Tech

19-40

10

Prostaglandins

Types of Prostaglandins

Essential fatty acids in the cell membranes produce prostaglandins. Prostaglandins regulate bodily functions in the heart, kidneys, liver, lungs, brain, nerves and the immune system.

In human beings, there are three families of prostaglandins, each of which is derived from a different fatty acid. Prostaglandin PG PGE1 PGF1 PGE2 PGF2 Eicosanoids Thromboxane A2 Leukotriene B4

Chemistry 121 Winter 2011 LA Tech

19-41

Chemistry 121 Winter 2011 LA Tech

19-42

Prostaglandins

Prostaglandins

Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid

Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20carbon polyunsaturated fatty acids in response to specific physiological triggers

9

7

5

1

3

8

6

4

2

12

14

16

18

CO 2 H

• one such polyunsaturated fatty acid is arachidonic acid

10 11

13

15

17

19

20

9

8

COOH

Prostanoic acid 13 11 12

14

15

Arachidonic acid

Chemistry 121 Winter 2011 LA Tech

19-43

Chemistry 121 Winter 2011 LA Tech

19-44

11

Prostaglandins

• among the prostaglandins synthesized biochemically from arachidonic acid are O

HO

9

9

COOH HO

11

Prostaglandins • the observation that PGF2 stimulates contractions of uterine smooth muscle led to the development of synthetic PGFs that can be used for therapeutic abortions

COOH

15

HO

OH

15

11

9

9

OH PGF2

PGE2

COOH

COOH HO

15

11

HO HO H

19-45

Prostaglandins

O

O COOH

COOCH3

HO

15 16

HO H PGE1

Chemistry 121 Winter 2011 LA Tech

19-46

Eicosanoids

• the PGE1 analog, misoprostol, is used to prevent the ulceration associated with the use of aspirin-like NSAIDs

HO

15

11

HO CH3 Carb op rost (15S)-15-Meth yl-PGF2 

PGF2 

Chemistry 121 Winter 2011 LA Tech

extra methyl group at carbon-15

HO

HO

HO

15

CH3

The prostaglandins are members of an even larger family of compounds called eicosanoids, all of which contain 20 carbons and are derived from polyunsaturated fatty acids • thromboxanes

16

9 8

1

COOH

O

Misopros tol 11

O

12

15

20

OH Th romboxane A2 (a potent vasocons trictor) Chemistry 121 Winter 2011 LA Tech

19-47

Chemistry 121 Winter 2011 LA Tech

19-48

12

Eicosanoids

Eicosanoids

Leukotrienes

Prostacyclin

• found primarily in white blood cells • one function is constriction of smooth muscles, especially those of the lungs

1

5

HOOC

6

O H

OH 11

9

1

7

20

6

COOH

O

Leu kotrien e C4 (LTC4) (a smooth mus cle con strictor)

Chemistry 121 Winter 2011 LA Tech

N H

HN

20

L-glutamic acid

O

19-49

Steroids A group of plant and animal lipids that have this tetracyclic ring structure

Chemistry 121 Winter 2011 LA Tech

15 13

COOH NH2

14

OH OH Pros tacyclin (a platelet aggregation inh ibitor)

glycine

14

L-cysteine

H

11

COOH

5

S

7

9 8

19-51

Chemistry 121 Winter 2011 LA Tech

19-50

Steroids Fats similar to, and usually synthesized from, cholesterol.

Chemistry 121 Winter 2011 LA Tech

19-52

13

Steroids Features common to steroids CH3

H

CH3

D

C A H

B H

H

• the fusion of rings is trans and each atom or group at a ring junction is axial • the pattern of atoms or groups along the ring junctions is nearly always trans-anti-trans-anti-trans • the steroid system is nearly flat and quite rigid • most have axial methyl groups at C-10 and C-13

Chemistry 121 Winter 2011 LA Tech

19-53

Chemistry 121 Winter 2011 LA Tech

19-54

Steroids

Steroids

Cholesterol

Androgens - male sex hormones • synthesized in the testes • responsible for the development of male secondary sex characteristics

H H3 C H3 C

*

HO

*

* * ** * *

Ch oles terol has 8 s tereocen ters ; 256 stereois omers are possible

H3 C

H

H H

H3 C

H

HO

H3 C

H This is the stereoisomer foun d in h uman metab olis m

H

H3 C H

O

H H

H

HO Testosterone

19-55

H3 C

H

H

O

Chemistry 121 Winter 2011 LA Tech

OH

Chemistry 121 Winter 2011 LA Tech

Androsterone

19-56

14

Steroids

Steroids

Anabolic steroid: a steroid hormone, such as testosterone, that promotes tissue and muscle growth and development

Estrogens: female sex hormones

HO H3 C CH3 H3 C

H3 C

H H

H H

O

H3 C

CH 3

H H

H

H

HO

O Meth androstenolone

HO CH3 H3 C

OH

H H

• synthesized in the ovaries • responsible for the development of female secondary sex characteristics and control of the menstrual cycle

N androlon e

H3 C

Methand riol

H3 C C=O H

H3 C

H

H

H

H

H

O 19-57

Estrone

Chemistry 121 Winter 2011 LA Tech

19-58

Synthetic Estrogens

Steroids

Progesterone-like analogs are used in oral contraceptives

Glucocorticoid hormones

"Nor" refers to the absence of a methyl group here. It is present in ethindrone

H H

O

• • • •

HO C CH H3 C H

H Norethindrone

synthesized in the adrenal cortex regulate metabolism of carbohydrates decrease inflammation involved in the reaction to stress CH 2 OH C=O H3 C OH

O H3 C

H H

H

C=O OH

H H

H

O Cortisone

19-59

CH 2 OH

H3 C

HO H3 C

O Chemistry 121 Winter 2011 LA Tech

H

HO Progesterone

Chemistry 121 Winter 2011 LA Tech

O

Chemistry 121 Winter 2011 LA Tech

Cortisol 19-60

15

Steroids

Steroids

Mineralocorticoid hormones

Bile acids

• synthesized in the adrenal cortex • regulates blood pressure and volume by stimulating the kidneys to absorb Na+, Cl-, and HCO3OH O

CH

• synthesized in the liver, stored in the gallbladder, and secreted into the intestine • emulsify dietary fats and aid in their absorption and digestion

CH2 OH C= O

H3 C H3 C

H3 C

COOH

H

H H

H

HO

H

O

H OH H Cholic acid

Aldosterone Chemistry 121 Winter 2011 LA Tech

19-61

Steroid Biosynthesis

Chemistry 121 Winter 2011 LA Tech

Biosynthesis Choresterol

The building block from which all carbon atoms of steroids are derived is the two-carbon acetyl group of acetyl-CoA

O CH3 -C-S-CoA Acetyl Coen zyme A

Stage 1: synthesis of isopentenyl pyrophosphate from three molecules of acetyl-CoA (Sect 16.5) Stage 2: synthesis of cholesterol Stage 3: conversion of cholesterol to other steroids

cholesterol

19-62

bile acids (e.g., ch olic acid) sex hormones (e.g., testosteron e and es trone) mineralocorticoid h ormon es (e.g., ald os terone) glucocorticoid hormones (e.g., cortisone)

O HO CH3 -

O OH (R)-Mevalonate

OP2 O6 3 Is op entenyl pyroph os phate C10 terpen es

( C1 0 ) Geranyl pyrophosp hate

C15 an d C20 terpen es

( C1 5 ) Farn esyl pyrophosp hate

C30 terpen es

( C3 0 ) Sq ualene Cholesterol

Chemistry 121 Winter 2011 LA Tech

19-63

Chemistry 121 Winter 2011 LA Tech

19-64

16

Fat-Soluble Vitamins

Vitamin A (Retinol)

Vitamins are divided into two broad classes on the basis of their solubility • those that are fat soluble (and hence classified as lipids • those that are water soluble

• occurs only in the animal world • found in the plant world in the form of a provitamin in a group of pigments called carotenes cleavage h ere

The fat-soluble vitamins include A, D, E, and K -Caroten e enzyme-catalyzed cleavage in the liver CH2 OH 2 Retin ol (Vitamin A) Chemistry 121 Winter 2011 LA Tech

19-65

Vitamin A

Chemistry 121 Winter 2011 LA Tech

19-66

Vitamin A

• isomerization of the double bond at C11-C12 is triggered by light striking rhodopsin

The best understood role of vitamin A is its participation in the visual cycle in rod cells • the active molecule is retinal (vitamin A aldehyde), which forms an imine with an -NH2 group of the protein opsin to form the visual pigment called rhodopsin • the primary chemical event of vision in rod cells is absorption of light by rhodopsin followed by isomerization of the 11-cis double bond to the 11-trans configuration

11-12 cis configu ration 11 12

CH= N-opsin light 11

CH= N-opsin 12

Chemistry 121 Winter 2011 LA Tech

19-67

Chemistry 121 Winter 2011 LA Tech

19-68

17

Vitamin A

• a group of structurally related compounds that play a role in the regulation of calcium and phosphorus metabolism • the most abundant form is vitamin D3

Vitamin E Vitamin E: a group of compounds of similar structure • the most active is -tocopherol • vitamin E functions as an antioxidant; it traps peroxy radicals of the type HOO• and ROO• formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids

UV ligh t

OH HO

V itamin E (-Tocoph erol)

7-D ehydrocholesterol

O

HO Vitamin D 3 Chemistry 121 Winter 2011 LA Tech

19-69

Vitamin K

• the name of this vitamin comes from the German word Koagulation, signifying its important role in the bloodclotting process O

Chemistry 121 Winter 2011 LA Tech

19-70

Nonglyceride Lipids Sphingolipids steroids, waxes

isoprene u nits

2

O

O

Vitamin K1

O Menadione (a synthetic vitamin K analog) Chemistry 121 Winter 2011 LA Tech

19-71

Chemistry 121 Winter 2011 LA Tech

19-72

18

Sphingolipids: Sphingosine

Sphingolipids

These lipids are based on sphingosine, are found in plants and animals, and are common in the nervous system.

CH

CH OH

CH OH

O CH NH C R1 CH2OH

ceramide N-acylsphingosine

Chemistry 121 Winter 2011 LA Tech

19-73

Sphingoglycolipids

CH CH2 12 CH3

CH CH CH2 12 CH3

Chemistry 121 Winter 2011 LA Tech

O CH NH C R1 O + CH2O P O CH2CH2N (CH3)3 O

sphingomyelin A ceramide with phosphocholine or phosphoethanolamine as 19-74 head group

Sphingolipids

Attachment of carbohydrates to primary -OH of ceramide Cerebrosides: contain a single moiety, principally galactose Sulfatides: sulfuric esters of galactocerebrosides Gangliosides: contain a complex oligosaccharide moiety

Chemistry 121 Winter 2011 LA Tech

19-75

Chemistry 121 Winter 2011 LA Tech

19-76

19

Clinical significance of sphingolipids

Sphingoglycolipids-2

Blood groups determined by various glycolipids on RBCs

CH2 CH CH CH CH CH2 O NH OH CH2OH CO O H H R1 OH H HO H H OH a cerebroside

12

CH3

Type 0

R

GlcNAc Fucose

Type A

R

Galactose Sialic acid (NANA)

R

Type B These compounds are found in the cell membranes of nerve and brain cells. Chemistry 121 Winter 2011 LA Tech

19-77

19-78

Anabolic steroids

Estrogens They are primarily responsible for the conversion of girls into sexually-mature women. Participate in the monthly preparation of the body for a possible pregnancy. Participate in pregnancy if it occurs

Chemistry 121 Winter 2011 LA Tech

Chemistry 121 Winter 2011 LA Tech

19-79

A number of synthetic androgens promote an increase in body weight and muscle strength: popular with athletes, weight lifters, cyclists, professional football players, etc. Often these athletes take doses 100 time greater than those used in standard therapy. Such illicit use Side effects: acne, a decrease in libido, testicle size, and sperm counts to name a few. Chemistry 121 Winter 2011 LA Tech

19-80

20

Complex lipids

Four major groups of plasma lipoproteins.

Lipoproteins Lipoproteins are composed of a neutral core of cholesterol and triacylglycerols. Glycolipids Sugar containing lipids

Chemistry 121 Winter 2011 LA Tech

19-81

1. Chylomicrons 2. Very low-density lipoproteins (VLDL) 3. Low-density lipoproteins (LDL) 4. High-density lipoproteins (HDL)

Chemistry 121 Winter 2011 LA Tech

19-82

Sphingolipids

The roles of HDL, LDL, and cholesterol. Cholesterol and lipoproteins are related plaque that causes heart attacks and most strokes. When LDL levels are low, atherosclerosis and heart attacks are almost unknown. High HDL levels are associated with a reduced risk of heart disease: "good" cholesterol

These lipids are based on sphingosine, are found in plants and animals, and are common in the nervous system.

CH

CH CH2 12 CH3

CH OH CH NH2 CH2OH sphingosine

Chemistry 121 Winter 2011 LA Tech

19-83

Chemistry 121 Winter 2011 LA Tech

19-84

21

Sphingoglycolipids

Sphingolipids CH CH CH2 12 CH3 CH OH

CH OH

O CH NH C R1 CH2OH

ceramide N-acylsphingosine

Chemistry 121 Winter 2011 LA Tech

Attachment of carbohydrates to primary -OH of ceramide

CH CH2 12 CH3

CH

O CH NH C R1 O + CH2O P O CH2CH2N (CH3)3 O

sphingomyelin A ceramide with phosphocholine or phosphoethanolamine as 19-85 head group

Sphingoglycolipids-2 CH2 CH CH CH O NH OH CH2OH CO O H H R1 OH H HO H H OH

Cerebrosides: contain a single moiety, principally galactose Sulfatides: sulfuric esters of galactocerebrosides Gangliosides: contain a complex oligosaccharide moiety

Chemistry 121 Winter 2011 LA Tech

19-86

Clinical significance of sphingolipids

CH CH2

12

CH3

Blood groups determined by various glycolipids on RBCs

Type 0

R

GlcNAc Fucose

R

Type A

Galactose Sialic acid (NANA)

R

a cerebroside Type B These compounds are found in the cell membranes of nerve and brain cells. Chemistry 121 Winter 2011 LA Tech

19-87

Chemistry 121 Winter 2011 LA Tech

19-88

22