Lipids

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• Lipids

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Lipids are non-polar (hydrophobic) compounds,
soluble in organic solvents.

• 1. Simple lipids esters of FA with alcohols
• Fats alcohol glycerol
• Waxes alcohol long-chain alcohol

• 2. Complex lipids esters of FA containing groups
  in addition to an alcohol and FA
• Phosholipids contain a phosphoric acid residue
• Glycolipids contain carbohydrate
• 3. Derived lipids e.g. steroids, carotenoids

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Major roles of lipid

• 1. They serve as structural components of
  biological membranes.
• 2. They provide energy reserves, predominantly
  in the form of triacylglycerols.
• 3. Lipid derivatives serve as vitamins and
  hormones.
• 4. Lipophilic bile acids aid in lipid
  solubilization.
• 5. Lipids serve as thermal and electrical
  insulators.

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Fatty Acids
Fatty acids consist of a hydrocarbon chain with a
carboxylic acid at one end. They are amphipathic,
having a non-polar end and a polar end. A 16-C
fatty acid CH3(CH2)14-COO- Non-polar
polar FA may be saturated or unsaturated.
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• A 16-C fatty acid with one cis double bond
  between C atoms 9-10 may be represented as
• 161 cis D9 or 161 cis ?7
• ?7 - double bond on the seventh carbon counting
  from
• terminal methyl carbon

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Double bonds in fatty acids usually have the cis
configuration. Most naturally occurring fatty
acids have an even number of carbon atoms.

• Some fatty acids and their common names
• 140 myristic acid 160 palmitic acid
  180 stearic acid
• 181 cisD9  oleic acid (?9)
• 182 cisD9,12  linoleic acid (?6)
• 183 cisD9,12,15  a-linolenic acid (?3)
• 204 cisD5,8,11,14  arachidonic acid (?6)
• 205 cisD5,8,11,14,17  eicosapentaenoic acid (?3)

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• In most FA the hydrocarbon chain is linear.
• There is free rotation about C-C bonds in the
  fatty acid hydrocarbon, except where there is a
  double bond.

Each cis double bond causes a kink in the chain.
The melting points of FA increase with chain
legth and decrease according to unsaturation.
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Triacylglycerols
Triacylglycerols (triglycerides) are the most
abundant dietary lipids. They are the form in
which we store energy.
Each triacylglycerol has a glycerol backbone to
which are esterified 3 fatty acids. Most
triacylglycerols are mixed. The 3 fatty acids
differ in chain length number of double bonds.
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Complex lipids

• Phospholipids
• Glycerophospholipids (PE, PS, PC plasmalogens)
• Sphingomyelins
• Glycolipids
• Cerebrosides
• Gangliosides

Sphingolipids
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Glycerophospholipids

• 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.
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Phosphatidic acid

• In phosphatidic acid
• fatty acids are esterified to hydroxyls on C1
  C2
• the C3 hydroxyl is esterified to Pi.

Phosphatidic acid is an intermediate in the
synthesis of triacylglycerols and
glycerophospholipids.
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Usually R1 unsaturated FA R2 saturated FA

• 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.

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• Each glycerophospholipid
• includes
• a polar region glycerol, carbonyl of
  fatty acids, Pi, the polar head group (X)
• non-polar hydrocarbon tails of fatty acids (R1,
  R2).
• ? They are amphipathic

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• Phosphatidylinositol (PI), with inositol as polar
  head group, is one glycerophospholipid.
• In addition to being a membrane lipid,
  phosphatidylinositol has roles in cell signaling.

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• Phosphatidylcholine (lecithin) PC, with choline
  as polar head group, is another
  glycerophospholipid.
• It is a common membrane lipid.
• Dipalmitoyl lecithin is major constituent of the
  surfactant.

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Plasmalogens

• Plasmalogens are glycerol ether phospholipids

They are found in brain and muscle
PAF (platelet activating factor) causes
platelet aggregation
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Sphingolipids
Sphingolipids are derivatives of the amino
alcohol sphingosine, which has a long hydrocarbon
tail.

• The amino group of sphingosine can form an amide
  bond with a fatty acid carboxyl, to yield a
  ceramide.
• Ceramides usually include a polar head group,
  esterified to the terminal OH of the sphingosine.

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Sphingomyelin, a ceramide with a phosphocholine
head group, is a common constituent of plasma
membranes.
Sphingomyelin is found in brain and nerve tissue.
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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 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.
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Steroids
Cholesterol, an important constituent of cell
membranes, has a rigid ring system and a short
branched hydrocarbon tail.
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• Cholesterol is largely hydrophobic.
• But it has one polar group, a hydroxyl, making it
  amphipathic.

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• Cholesterol is the precursor for the synthesis
• D vitamin
• Bile acids
• Sex hormones
• Adrenocortical hormones

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Amphipathic lipids in association with water form
complexes in which polar regions are in contact
with water and hydrophobic regions away from
water.

• Depending on the lipid, possible molecular
  arrangements
• Various micelle structures. E.g., a spherical
  micelle is a stable configuration for fatty
  acids.
• A bilayer. This is the most stable configuration
  for amphipathic lipids such as phospholipids.

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Membranes

• Membrane consists of phospholipids bilayer with
  proteins inserted in it or bound to the surface.

• Integral proteins are embedded in the bilayer
• Peripheral proteins are bound to the surface of
  the
• membrane
• Many of the proteins and lipids carry
  oligosaccharide
• chain

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Membrane fluidity The interior of a lipid
bilayer is normally highly fluid.
In the liquid crystal state, hydrocarbon chains
of phospholipids are disordered and in constant
motion. At lower temperature, a membrane
undergoes transition to a crystalline state in
which fatty acid tails are fully extended,
packing is highly ordered.
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• 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.

Interaction with the relatively rigid cholesterol
decreases the mobility of hydrocarbon tails of
phospholipids.
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Lateral mobility of a lipid, within the plane of
a membrane, is depicted at right.
Flip-flop of lipids (from one half of a bilayer
to the other) is normally very slow. Flip-flop
would require the polar head-group of a lipid to
traverse the hydrophobic core of the membrane.
The two leaflets of a bilayer membrane tend to
differ in their lipid composition.
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Lipoproteins

• Since nonpolar lipids are insoluble in water,
  for transport in blood they are combined with
  amphipathic lipids and proteins to make
  water-miscible lipoproteins

Lipoproteins consist of nonpolar core that is
surrounded by a layer of phopholipids and
cholesterol
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Lipoproteins

• Chylomicrons
• transport triglycerides from intestine to other
  tissue
• Very low density lipoproteins (VLDL)
• bind triglycerides in liver and curry them to
  fat tissue
• Low-density lipoproteins (LDL)
• carry cholesterol to peripheral tissues
• High-density lipoproteins (HDL)
• transport cholesterol to liver