dr. arrel toews (say tavz, like waves) 420 me jones building atoews@med.unc.edu 843-8727 get up to...
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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
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