Dr. Arrel Toews (say Tavz, like waves) 420 ME Jones Building atoews@med.unc.edu 843-8727 Get UP To Speed (GUTS) Session on Lipids A primer on lipid structure,

Dr. Arrel Toews (say Tavz, like “waves”)

420 ME Jones Building

atoews@med.unc.edu

843-8727

Get UP To Speed (GUTS) Session on Lipids

A primer on lipid structure, nomenclature, and function

See also the GUTS session on Lipids notes (.doc) - self-assessment exam - additional lipid information

Definition: biomolecules that are overall hydrophobic

- very non-polar

- insoluble in water/aqueous solutions (cellular environment)

- soluble in “organic” (non-polar) solvents (CHCl3-MeOH)

- operational rather than structural definition

Lipids

(water-fearing)

- contrast this with definitions for:

proteins

nucleic acids

carbohydrates

- energy source (dietary triglycerides)- energy stores (adipose tissue triglycerides)

- triglycerides are completely hydrophobic highly reduced (energy-rich) compact, efficient energy storage

- membranes – amphipathic lipids (both hydrophobic and hydrophilic portions) - phospholipids - sphingolipids - cholesterol

Lipid Functions

Fatty acids are basic building block of most lipids

- signaling molecules 2nd messenger systems; eicosanoids; steroid hormones

- fat-soluble vitamins: A (vision), D (bones/teeth), E (anti-oxidant; live forever), K (blood clotting)

H H H H H H H H H H H H H H H H H O l l l l l l l l l l l l l l l l l llH―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C―C-O- l l l l l l l l l l l l l l l l l H H H H H H H H H H H H H H H H H

Stearic acid CH3(CH2)16COOHSystematic: octadecanoic acid

Shorthand: 18:0 (18C, no double bonds)

Structure and nomenclature of fatty acids

*All fatty acids ionized at physiological pH; pKa <5

*

O llCH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2C-O-

*

OllC-O-

*

Long-chain carboxylic acids; building blocks of most lipids

Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO

OHSystematic: cis, cis 9,12-octadecadienoic acid

Shorthand: 18:26

This is shorthand for a fatty acid with 18 carbons and 2 double bonds. The 6 indicates the double bond closest to the methyl end is 6 carbons from the end.

Structure and nomenclature of fatty acids

If more than one double bond, the configuration is always “methylene-interrupted” (-CH=CH-CH2-CH=CH-) with

cis double bonds. Always 3C between C=C bonds

So - the term 18:26 completely defines the formula and structure of linoleic acid

Structure and nomenclature of fatty acids

-designation important in nomenclature“-oxidation” of fatty acids

CH3(CH2)14COOH

CH3(CH2)5CH=CH(CH2)7COOH

CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH

CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH

CH3(CH2)CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)2

COOH

Try this at home: write shorthand names for the FA below

Write the chemical formulas for 18:19 and 20:53

O llCH3―(CH2)n―CH2―CH―C-O-

18or

whatever

generic fatty acid3 2 1

“systematic”

“biochemists”

no matter how long

Fatty Acids: long-chain carboxylic acids

“kinks” – less packing – more fluid GOOD for membranes

trans-FA are BAD! – no kinks, pack tightly; LDL; HDL (partially hydrogenated vegetable oils, Crisco, margarine)

O ll*really C―O-

usually attached to glycerol as PL or TG

Virtually all natural C=Cdouble bonds are cis

CC COOH3HC

H

H

CC COOH3HC

H

H

CC COOH

3HC

H

H

CC COOH

3HC

H

H

cis-fatty acid

trans-fatty acid

COOH3HCCOOH3HC

saturated fatty acid

hydrophobicity (long chain length) andfluidity (liquid at body temperature)

both vital required biophysical properties - cell membranes - storage depots of energy (adipose tissue)

Physiological functions of lipids – a problem

But melting point increases with chain length

So FA long enough to be hydrophobic are solids! (mp is above body temp)

How does Mother Nature handle this??

18Cfatty acids

Number of carbon atoms2 4 6 8 10 12 14 16 18 20 22 24

Melt

ing

tem

pera

ture

(°C

)

-20

-10

0

10

20

30

40

50

60

70

80

90

— Linolenic acid(18:3)

Saturated fatty acidsStearic acid

(18:0)

Oleic acid(18:1)

Linoleic acid(18:2)

Melting points of fatty acids

18:4-57C

Body temperature

The fatty acid composition of membrane lipids and adipose tissue triglycerides - chain length - degree of unsaturationis carefully regulated to maintain the appropriate fluidity

Physiological functions of lipids

– much of it as triglyceride (mostly in adipose tissue) – also lots in phospholipids (major components of membranes)

Most of the fatty acid in the body is esterified

O llCH2OC

O llCH2OC

O

llCHO C

glycerol

Fatty acid composition is regulated to maintain correct fluidity (both TG and PL) - critical to biological function

fatty acid

fatty acid

fatty acid

Triglycerideenergy sourcestorage form

Phospholipids – vital components of membranes

- glycerol backbone (like TG)- 2 FA in ester linkages- phosphate + X (choline, ethanolamine, serine, inositol)- amphipathic (amphi = both)

GLY

CER

OL F A T T Y A C I D

F A T T Y A C I D

P

e.g.,

ch

olin

e+

THE defining components of biological membranes - make lipid bilayers (2 molecules thick)

Remember kinks in cis-double bonds of unsat’d FA

polar head long hydrophobic tail

Oll

CH2 O C

CH2

CH O CllO

Oll

P OlO-

3HC―N- CH2- CH2 O

CH3l

lCH3

+

phosphate

glycerol

Phosphatidylcholine (PC)

Choline(polar “X”)

2 long-chain fatty acids

aka lecithina prominent phospholipid

major membrane componentinvolved in cholesterol handling too

FA heterogeneity means many molecular species of PC

Oll

CH2 O C

CH2

CH O CllO

fatty acid

fatty acidOll

P OlO-

H- C- CH2 O

NH3l

lC

O O-

+

serine

Oll

CH2 O C

CH2

CH O CllO

fatty acidfatty acid

fatty acid

fatty acidOll

P OlO-

H- C- CH2 O

NH3l

lC

O O-

+

serine

Phosphatidylserine (PS)

Oll

CH2 O C

CH2

CH O CllO

fatty acidfatty acid

fatty acid

fatty acidOll

P OlO-

OOHl

HOl

lHO

l

l

I nositol-bis-phosphate

Phosphatidylinositol-bisphosphate (PIP2)

P

P

membranes

2nd messengersignalingsystems

Oll

CH2 O C

CH2

CH O CllO

fatty acid

fatty acidOll

P OlO-

3HN-CH2-CH2 O+

ethanolamine

Oll

CH2 O C

CH2

CH O CllO

fatty acid

fatty acidOll

P OlO-

3HN-CH2-CH2 O+

Oll

CH2 O C

CH2

CH O CllO

fatty acidfatty acid

fatty acid

fatty acidOll

P OlO-

3HN-CH2-CH2 O+

ethanolamine

Phosphatidylethanolamine (PE)

Sphingolipids

GLY

CERO

L

FATTY ACID

FATTY ACID

P

chol

ine

polar head long hydrophobic tail

GLY

CERO

L

FATTY ACID

FATTY ACID

P

chol

ine

chol

ine

polar head long hydrophobic tail

Structures and properties are generally similar to phospholipids (amphipathic)

Phospholipids

GlycosphingolipidsF A T T Y A C I D

O

(usually)

Long-chain amino alcohol (sphingosine)sugar(s)

polar head long hydrophobic tail

(more on these in“Complex CH2O”GUTS session)

Amphipathic nature of PL and sphingolipids is vitalto life; makes membranes

Lots more on this in Dr. Jacobson’s Membranes GUTS lecture

Phospholipidor glycolipid

Polarhead

Hydro-phobic

tail

Micelle

water

water

Lip

id b

ilayerwate

r water

wat

er

water

Hydrophobic tails hide from water

1

2

34

56

7

89

10

1112

13

14 15

16

17

18

19

20

21

22 23 24 25

26

27

HO

CH3

CH3CH

CH3

CH3

CH3

CH2 CHCH2CH2

1

2

34

56

7

89

10

1112

13

14 15

16

17

18

19

20

21

22 23 24 25

26

27

HO

CH3

CH3CH

CH3

CH3

CH3

CH2 CHCH2CH2

Cholesterol

- rigid ring structure

polar

- “a little bit” amphipathic- membrane component (affects fluidity)- lipid transport in blood (atherosclerosis, &c)

Vocabulary – do you know the meaning of the following terms?

lipid

hydrophobic vs hydrophilic

amphipathic

fatty acid

saturated vs unsaturated FA

cis vs trans C=C double bonds

shorthand nomenclature for FA

triglyceride (and mono- and diglyceride)

phospholipid

sphingolipid

cholesterol