dr. arrel toews (say tavz, like waves) 420 me jones building [email protected] 843-8727 get up to...
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Dr. Arrel Toews (say Tavz, like “waves”)
420 ME Jones Building
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
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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
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- 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)
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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
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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
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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
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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
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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??
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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
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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
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– 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
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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
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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
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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)
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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)
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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
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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)
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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