7.8. lipids
TRANSCRIPT
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