LIPID STRUCTURE

1
Lipid Structure
Reza Meshkani, PhD Department of
Biochemistry Faculty of Medicine Tehran
University of Medical Sciences
2
Introduction
Introduction

• The role of Lipids
• Main components and Properties of Lipids
• Classification of lipids
• - Triglycerides
• Phospholipids
• Sterols
• Ecosanoids
• Isoprenoids
• 4-Lipid Digestion
• 5- Transport of lipids
• 6- Lipoprotein Metabolism

3
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4
Lipids Functions

• Provide Energy (9 kcal/g).

2. Protects vital organs against shock.
3. Insulates body against temperature extremes.
4. Carrier of fat soluble vitamins A,D,E, and K.
5. Give flavor to foods.
6. Important components of membranes
7. Helps body use carbohydrates and protein
efficiently
5
Lipid Components
Lipid Components
Fatty acids
Alcohol
Ester bandR1COOR2 Amid bandR1CONR2
Glycerol Phosphoglycerol Sterols Sphingosine
Saturated Unsaturated
6
Fatty Acids
long chain linear hydrocarbons carboxylic
acids Usually have an even number of C atoms
(usually 12 to 20) The carbons are numbered
starting from the carboxylic C. They are
amphiphilic they have a polar end and rest of
the molecule is nonpolar Fatty acids may be
saturated (no double bonds) or unsaturated (one
or more double bonds) All naturally occurring
double bonds have a cis-configuration Longer
chain and saturation increases melting point of
FA
7
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8
Function of Fatty Acids

• 1. Fuel and energy metabolism free fatty acids
  and triglyceride
• 2. Membrane structure complex lipids
• 3. Cholesterol metabolism cholesteryl ester is
  the major form in which cholesterol is
  transported or stored
• 4. Metabolic regulators free fatty acids,
  eicosanoids, complex lipids

9
Length of Fatty Acids
1. Short Chain fatty acids Less than 6 carbons
(most in dairy products)
2. Medium Chain fatty acids 6-10 carbons
3. Long Chain fatty acids 12-22 carbons (most
common in the diet)
10
Nomenclature

• 1- Based on hydrocarbon molecule with the number
  and arrangement of carbon atoms
• saturated anoic octanoic acid (octa 8)
• unsaturated enoic octadecenoic acid (octa 8
  and deca 10, thus 18)

• Palmitic (hexadecanoic)160
• Palmitoleic acid 9-hexadecenoic acid
• Stearic acid Octadecanoic acid) 180
• Oleic Acid (?9,-octadecenoic)181 ? 9
• Arachdonic acid (? 5,8,11,14-eicosatetraenoic
  acid)

11
Nomenclature

• 2- Terminal methyl carbon (CH3) as n-carbon or
  ?-carbon

• The carbon atom adjacent to the carboxyl carbon
  (No.2) is known as the a carbon

• ?9 indicates first or only double bond on the
  ninth carbon counting from the terminal methyl
  (omega) carbon (n)

12
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Nomenclature

• 3- unsaturated where is/are double bond(s)?
• . ?9 double bond between carbon atoms 9 and 10
• ?9,12 double bonds between 9 and 10, 12 and 13

14
Nomenclature

• 4-Classical name

15
Fatty Acids
??Saturated Fatty acids No double bonds 1.
lauric acid (laurate) (120) 2. myristic acid
(myristate) (140) 3. palmitic acid (palmitate)
(160) 4. stearic acid (stearate) (180)
Monounsaturated Fatty Acids ?? One double bond 1.
Oleic acid (oleate) (181cis) 2. Elaidic acid
(elaidate) (181trans)
Polyunsaturated Fatty Acids ?? Two or more double
bonds 1. Linoleic acid (linoleate) (182 9,12)
?6 2. Linolenic acid (linolenate) (183 9,12,15)
?3 3. Arachidonic acid (arachidonate) (204
5,8,11,14) ?6
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? 3 and ?6 Fatty acids
Omega-3 ?-3 fatty acids (Linolenic) are found
mainly in fish and fish products. ?-3 FAs
inhibit formation of thromboxane A2 (an
eicosanoid) required for platelet aggregation and
clot formation. Thus, ?-3 FAs decrease the risk
of heart disease
Omega-6 Linoleic acid Vegetable oils (corn,
safflower, soybean, cottonseed, sesame,
sunflower) Arachidonic acid Meats (can be made
from linoleic acid)
17
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18
Palmitic acid,

• The most common saturated fatty acid found in
  animals and plants.
• Palmitic acid is the first fatty acid produced
  during Lipogenesis (fatty acid synthesis)
• Intake of palmitic acid increases risk of
  developing cardiovascular diseases.

19
Arachidonic acid

• is present in the phospholipids
• involved in cellular signaling as a lipid second
  messenger

20
Why are these essential?

• In most mammals, double bonds can be formed at
  the ?4, ?5, ?6, and ?9 positions, but never
  beyond ?9, therefore any fatty acid that needs to
  add a double bond after ?10 for example are
  essential

• all saturated fatty acids are nonessential
• all monounsaturated fatty acids are nonessential

Essential FFA functions Needed for eicosanoid
production Part of structural lipids of the
cell and add structural integrity of
mitochondrial membrane Necessary for fetal
development, brain, and retina (vision)
21
Properties of Fatty acids
22
Saponification

• Alkali hydrolysis of fatty acids
• R-COOH NaOH, KOH RCOONaH2O

23
Isomeration

• saturated fatty acids (zig zag pattern)

• unsaturated fatty acids
• cis acyl chains are on the same side of the
  double bond (nearly all naturally occurring fatty
  acids)
• 2. trans acyl chains are on opposite sides of
  the bond
• ?? present in certain foods
• ?? Most arise due to partial hydrogenation
  (saturation) of polyunsaturated fatty
• acids of natural oils (margarine)

24
Hydrogenation

• Hydrogenation process of replacing some double
  bonds of polyunsaturated fats with hydrogen
  atoms. The process by which vegetable oil becomes
  margarine.

• When vegetable oils are hydrogenated, some
  double bonds undergo a change in configuration
  and are concerted to Trans Fatty Acids.

The Cis configuration is typical of the fatty
acid in natural foods.
The Trans fatty acids (formed during
hydrogenation) may raise LDL and lower HDL level.
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Melting Temperature
?? melting points of even-numbered carbon fatty
acids increase with chain length and decrease
according to unsaturation ?? saturated,
long-chain fatty acids are solid at body
temperature (high melting point) ??
polyunsaturated fatty acids are liquid at 0C
(low melting point) The membrane lipids, which
must be fluid at all environmental temperatures,
are more unsaturated Question?
27
Lipid peroxidation

• Peroxidation (auto-oxidation) of lipids is
  responsible for deterioration of foods and also
  damage of tissues which causes cancer,
  inflammatory disease, atherosclerosis, etc.
• The reaction is initiated by an existing free
  radical (X .), by light or by metal.
• The deterioration effects cause by free radicals
  (ROO ., RO. , OH. ) produced during peroxide
  formation from fatty acids (unsaturated)

28
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29
Lipid peroxidation

• Anti-oxidants
• - BHA (butylated hydroxyanisole) and BHT
  (butylated hydroxytoluene) are antioxidants used
  as food derivates
• Vit E, C, Beta carotene, glutathion(?????????
  ???? ???? ????? ???)
• Catalase, superoxid dismutase, lipooxygenase
• Polyunsaturated fats spoil more easily than
  saturated fats.
• Rancidity Flavor and odor of fat is affected,
  due to the oxidation of double bonds.
• To protect polyunsaturated fats from rancidity
• 1. Refrigeration
• 3. Hydrogenation

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Alcohol
31
Glycerol is the basis of Triglyceride
Phosphoglycerol is basis of Phospholipids
32
Sterol
Sterols Lipids containing multiple rings of
carbon atoms. Are essential components of cell
membranes and many hormones Are manufactured in
our bodies and therefore are not essential
components of our diet
????? ????????????? ???????
Sterols are basis of Cholesterol, Bile Acids,
Steroid hormones and Vitamin D
33
Sphingosine
CH3-(CH2)12-CHCH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
34
Classification of Lipids
35
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Triglycerides
In Triacylglycerol (TG) all 3 OH of glycerol
are esterified by FAs. Monoacylglygerol and
diacylglycerol have, respectively, 1 and 2 FAs
Naturally occurring glycerol is L-glycerol. TG
are the storage form of FA most dietary fats are
triglycerides Physiologically, TG are digested
in the small intestine by the enzyme pancreatic
lipase Monoacylglycerols are absorbed through
the intestinal cells, re-converted to TG and
assembled into lipoproteins
37
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38
Triglycerides
Fatty acids can differ in Length of their
carbon chain Short-, medium-, or long-chain
Level of saturation Saturation refers to how
many hydrogen atoms surround each carbon
Shape The shape of a triglyceride is determined
by the saturation of the carbon chains.
Saturated fatty acids can pack tightly together
and are solid at room temperature. For example
animal fats, butter, and lard are high in
saturated fatty acids. Unsaturated fatty acids
do not stack together well and are liquid at
room temperature. Plant oils have unsaturated
fatty acids.
Normal Plasma TG levels lt150mg/dl
39
Phospholipids
40
General Structure of Glycerophospholipid
41
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X
Net Charge pH 7 -1
General Structure of glycerophospholipids
Phosphatidate
43
Phosphatidyl Choline (Lecithin)

• High amount of circulation PL (69)
• A PL that is used in plasma membrane
• The most common PL in the membrane
• PLC is a store of Choline in the body
• Dipalmitoyl Lecithin is a surfactant

Net Charge pH 7 0
44
Phosphatidylcholine

• Functions
• Choline is required for the proper metabolism of
  fats
• -Facilitates the movement of fats in and out of
  cells. In liver, it exports the fat from the
  hepatocytes (Choline deficiencyFat
  accumulation, fatty liver, cirrhosis)

• Like Vitamin B12, 5-adenosylmethionine, and
  Folic Acid, choline acts in the human body as a
  methyl donor.

• Choline is needed for cell membrane integrity
  because of the critical role it plays in the
  manufacture of primary components of cell
  membranes, such as phosphatidylcholine and
  sphingomyelin.

• Choline is essential in the synthesis of
  acetylcholine. Choline supplementation increases
  the accumulation of acetylcholine which plays a
  crucial role in many brain processes, including
  memory.

• Phosphatidylcholine increases the solubility of
  cholesterol and thereby decreases
• cholesterols ability to induce atherosclerosis.

45
Therapeutic Uses

• Liver Disorders
• Detoxification
• Hypercholesterolemia and Atherosclerosis
• Manic depressive disorder
• Alzheimers Disease

46
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47
Prostaglandines Leukoterines Tromboxane Prostacycl
ine
Arachidonic Acid
Phospholipase A2

• Lysolecithin
• At high concentration acts a Emulicification of
  triglycerides

Phosphatidyl CholineLecithin
48
Cholesterol ester
LCAT (Lecitin Cholesterol Acyl Transferase)
Fatty Acid

• Lysolecithin
• 7 of Plasma membrane PL

Phosphatidyl CholineLecithin
49
Ether Lipids(Plasmalogen phosphatidal
Platelete activating factor PAF)

• Similar to Lecithin, except that instead of
  ester link, they have ether link
• Plasmalogen has unsaturated Acyl group and PAF
  has saturated

• Plasmalogen (Phosphatidal)
• The heart of vertebrates is rich of ether lipids
• The importance is unknown, it seems that these
  ether link protected phospholipids from
  phospholipase activity
• PAF
• Released from Basophiles and stimulated platelet
  to secrete Serotonin

50
Phosphatidyl 4,5 bisphosphate
DiacelglycerolDAG
Inositol 3 phosphateIP3
Phospholipase C
DAG Activation of protein kinase C and
phosphorylation of target proteins
IP3 Release of Ca from endotelium And regulating
activation of proteins
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Phosphatidyl Ethanolamine (Cephalin)

• 5 of circulation PL
• Isolated from Brain

Net Charge pH 7 0
52

• Phosphatidylethanolamine is the second most
  abundant phospholipid in animal and plant lipids
  and is the main lipid component of microbial
  membranes.
• It can amount to 20 of liver phospholipids and
  as much as 45 of those of brain
• In contrast to phosphatidylcholine, it is
  concentrated with phosphatidylserine in the inner
  leaflet of the plasma membrane.

• Functions
• secretion of the nascent very-low-density
  lipoproteins from liver
• membrane fusion and fission???? ???? ??????
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• Integration of plasma membrane

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Phosphatidyl Glycerol
Net Charge pH 7 -1
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Cardiolipin
Phosphatidyl Glycerol Phosphatidic Acid
Inner mitochondrial membrane, where it
constitutes about 20 of the total lipid
composition.

• Is seen in mitochondria and chloroplast

Net Charge pH 7 -1
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Cardiolipin

• Cardiolipin (bisphosphatidyl glycerol) is an
  important component of the inner mitochondrial
  membrane, where it constitutes about 20 of the
  total lipid

• Functions
• Regulates aggregate structures
• Helps to build quaternary structure
• Triggers apoptosis
• Serves as proton trap for oxidative
  phosphorylation
• Cholesterol translocation from outer to the
  inner membrane of mitochondrial
• Import protein into mitochondrial

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Clinical significance

• - Barth syndrome
• disease state (an infantile cardiomyopathy)
  linked to the X-chromosome, is associated with
  marked abnormalities in the composition of
  cardiolipin
• It has a mutation in the gene coding for Tafazzin
  (an acyltransferase), an enzyme involved in the
  biosynthesis of cardiolipin. Girls heterozygous
  for the trait are unaffected.
• -Diabetes
• -Cancer
• (A study published in 2009 suggests that
  cardiolipin abnormalities "can underlie the
  irreversible respiratory injury in tumors .
  Cardiolipin is an essential part of one pathway
  which triggers apoptosis (cell death)

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Phospholipases
PI45BP
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Indican Cobra
Eastern Diamondback Rettlesnake

• The Poisonous Snakes contain phospholipase A2
  that breakdown Lecithin and produces Lysolecithin
• Lysolecithin acts a detergent and dissolves of
  membrane of red blood cells.

61
Sphingolipids
62
Sphingosine
Sphingosine H Ceramide
63
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64
SphingophospholipidSphingomyelin
Phosphocholine

• The most common sphingolipid
• Is found in Central nervous system and Myelin
  membrane

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SphingoglycolipidCerebrosides

• Sphingosine Glucose Glucocerebroside (found
  in RBC, WBC, Membrane)
• Sphingosine Galactose Galactocerebroside
  (found in Brain)
• Galactocerebroside Sulfate Sulfatide

66
GangliosidesComplex Cerebroside
GM1
O antigen
A antigen
B antigen
67
Ganglioside

• Ganglioside is a compound composed of a
  glycosphyngolipid with one or more sialic acid
  (n-acetylneuraminic acid, NANA)
• The 60 known gangliosides differ mainly in the
  position and number of NANA residues.
• Location
• on cell surfaces, with the 2 hydrocarbon chains
  of the ceramide moiety embedded in the plasma
  membrane and the oligosaccharides on the
  extracellular surface.
• They are found predominantly in the nervous
  system where they constitute 6 of all
  phospholipids.
• Function (?? ?????)
• Gangliosides, glycosphingolipids, and
  glycoproteins found on the surface of
  oligosaccharide provide cells with distinguishing
  surface markers that can serve in cellular
  recognition (signal transduction) and
  cell-to-cell communication

68
Ganglioside nomenclature

• common gangliosides GM1, GM2, GM3, GD1a, GD1b,
  GT1a, GT1b, Gq1b
• letter G refers to the name ganglioside
• the subscripts M, D, T and Q indicate mono-, di-,
  tri, and quatra(tetra)-sialic-containing
  gangliosides
• the numerical subscripts 1, 2, and 3 designate
  the carbohydrate sequence attached to ceramide

69
Ganglioside nomenclature

• Numerical subscripts
• 1. Gal-GalNAc-Gal-Glc-ceramide
• 2. GalNAc-Gal-Glc-ceramide
• 3. Gal-Glc-ceramide

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A ganglioside (GM1)
71
Gangliosidoses (Lipid Storage Diseases)

• Mutations in genes coding for enzymes of
  ganglioside metabolism
• Tay-sachs disease (deficiency of beta
  galactosidase)
• Sandhoff disease (Deficiency in hexoseaminidase)

72
Waxes
73
Steroids
Sterols Cholesterol, Stigmasterol,Sitosterol Stero
id Hormones progesterone, cortisol,
Aldosterone testosterone Estradiol calcitriol Bi
le acids primary bile acids Cholic
acid Chenodeoxycholic acid secondary bile
acids lithocholic acid deoxycholic acid Vitamin
D
74
Cholesterol

• Component of cell membranes
• Can be made by the body
• Not an essential nutrient
• Forms the major parts of the plaques that narrow
  arteries in atherosclerosis
• The underlying cause of heart attacks and
  strokes
• Exclusively synthesized by animals
• Not readily catabolized for energy
• Present in all tissue
• Converted in liver to bile acids
• Converted by gonads and adrenals into steroid
  hormones

75
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  sitosterol-stigmastrol
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76
Cholesterol and cholesterol esters
77
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78
Bile Acids
79
Steroids Hormones
80
(No Transcript)
81
Progesterone
It is synthesized in the corpus luteum of the
ovaries. The hormone prepares the uterus for a
possible pregnancy. The development of the
mammary glands is also stimulated by progesterone
82
Estradiol
Estradiol is the most important of the estrogens.
Like progesterone, it is synthesized by the
ovaries and, during pregnancy, by the placenta as
well. Estradiol controls the menstrual cycle.
It promotes proliferation of the Uterine mucosa,
and is also responsible for the development of
the female secondary sexual characteristics
(breast, fat distribution)
83
Cortisole
Cortisol, the most important glucocorticoid, is
synthesized by the adrenal cortex. It is
involved in regulating protein and carbohydrate
metabolism by promoting protein degradation and
the conversion of amino acids into glucose. As
a result, the blood glucose level rises.
Synthetic glucocorticoids (e. g., dexamethasone)
are used in drugs due to their anti-inflammatory
and immunosuppressant effects.
84
Testosterone
Testosterone is the most important of the male
sexual steroids (androgens). It is synthesized
in the Leydig intersitial cells of the testes,
and controls the development and functioning of
the male gonads. It also determines secondary
sexual characteristics in men (muscles, hair,
etc.).
85
Aldosterone
Aldosterone, a mineralocorticoid, is also
synthesized in the adrenal gland. In the
kidneys. it promotes Na resorption by inducing
Na/K ATPase and Na channels. At the same
time, it leads to increased K excretion. In this
way, aldosterone indirectly increases blood
pressure.
86
Calcitriol
Calcitriol is a derivative of vitamin D.
Calcitriol itself is synthesized in the kidneys.
Calcitriol promotes the resorption of calcium
in the intetine and increases the Ca2 level in
the blood.
87
Vitamin D
88
Eicosanoid Hormones

• Eicosanoid horomones are synthesized from
  arachadonic acid (204).
• Prostaglandins
• Prostacyclins
• Thromboxanes
• Leukotrienes

89
Eicosanoid Hormones

• Eicosanoids are oxygenated derivates of
  polyunsaturated 20-carbon fatty acids
• Most cells, except red blood cells, produce
  eicosanoids,
• Have profound physiological effects at extremely
  low concentrations.
• They have specific effects on target cells close
  to their site of formation.
• They are rapidly degraded, so they are not
  transported to distal sites within the body.
• Effects
• -Inflammatory response to damaged tissue
• - Production of pain and fever
• - Regulation of blood pressure
• -Induction of blood clotting
• - Control of reproduction functions
• - Regulation of sleep/wake cycle

90
Eicosanoid

• Prostaglandins all have a cyclopentane ring.
• A letter code is based on ring modifications
  (e.g., hydroxyl or keto groups).
• A subscript refers to the number of double bonds
  in the two side-chains.

Prostacyclin Prostaglandin I2 (PGI2)
91
SUBSTITUTION PATTERN OF PROSTANOIDS
92
EICOSANOIDS
Eicosanoids act via membrane receptors in the
immediate vicinity of their site of synthesis,
both on the synthesizing cell itself (autocrine
action) and on neighboring cells (paracrine
action).
Physiological functions of eicosanoids.
93
Eicosanoid Hormones
inhibited by glucocorticoids
inhibited by aspirin, ibuprofen
Or Cyclooxygenase (COX)
94
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  ????????????? ??? ??? ????? ??? ?????? ???? ???
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95

• Prostaglandin H2 Synthase catalyzes the
  committed step in the cyclic pathway
• PGH2 Synthase is a heme-containing dioxygenase,
  bound to ER membranes.
• (A dioxygenase incorporates O2 into a
  substrate).
• PGH2 Synthase exhibits 2 activities
  cyclooxygenase peroxidase.
• PGH2 Synthase (expressing both cyclooxygenase
  peroxidase activities) is sometimes referred to
  as Cyclooxygenase, abbreviated COX.
• Non-steroidal anti-inflammatory drugs (NSAIDs),
  such as aspirin and derivatives of ibuprofen,
  inhibit cyclooxygenase activity of PGH2 Synthase

96
Effects of Prostaglandins

• Stimulate or inhibit smooth-muscle contraction
• Inhibit HCl secretion in the stomach,
  particularly PGE1
• Promote mucus secretion, which protects the
  gastric mucosa against the acid.
• In the immune system, prostaglandins attract
  leukocytes to the site of infection
• PGF2a causes constriction of the uterus
• PGE2 is applied locally to help induce labor at
  term

97
NSAIDs (Non steroid anti-inflammatory drugs)

• Acetylsalicylic acid and related non-steroidal
  anti-inflammatory drugs (NSAIDs) selectively
  inhibit the cyclooxygenase activity of
  prostaglandin synthase and consequently the
  synthesis of most eicosanoids.
• Aspirin acetylates a serine hydroxyl group near
  the active site, preventing arachidonate binding.
  The inhibition by aspirin is irreversible
• Most other NSAIDs, such as indomethacin and
  ibuprofen, inhibit cyclooxygenases by competing
  with arachidonate.

98

• Side effects of NSAIDs
• Impairing hemostasis because of inhibiting
  synthesis of thromboxanes by thrombocytes
• Increasing HCl secretion and inhibiting the
  formation of protective mucus.
• Long-term NSAID use damages the gastric mucosa.

99
Selective COX inhibitors

• Celecoxib
• Rofecoxib
• Because COX-2 is usually specific to inflamed
  tissue, there is much less gastric irritation
  associated with COX-2 inhibitors, with a
  decreased risk of peptic ulceration.

100
Lipid transport in the circulation
Lipids are insoluble in plasma. In order to be
transported they are combined with specific
proteins to form lipoproteins
Proteins (apoproteins)
Non polar lipids in core (TAG and cholesterol
ester)
Cholesterol

• Apoproteins are only weakly associated with a
  particular lipoprotein and are easily transferred
  to another lipoprotein of a different class.
  Apoproteins have various functions including 
• Structural role 
• Binding sites for receptors 
• Activators or co-enzymes for enzymes involved
  with lipid metabolism 

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Physiological Function

• Transport lipid from exogenous (diet) or
  endogenous (de novo synthesis) sources for
  delivery to cells and tissues for energy, storage
  or building block components
• Transport fat-soluble vitamins
• Transport fat-soluble drugs
• Delivery of cholesterol to steroid hormone
  producing tissues
• They have a critical role in atherosclerosis

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Functions of Apoproteins (Apo)
Structural Serve to stabilize and maintain
the molecular structure of the molecule
Regulatory Cofactors for enzymes involved in
lipoprotein metabolism
Mediation Serve as ligands for lipoprotein
interactions with receptors
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Apoproteins of human lipoproteins

• A-I (28,300)- principal protein in HDL
• 90 120 mg in plasma activates LCAT

• A-II (8,700) occurs as dimer mainly in HDL
• 30 50 mg enhances hepatic lipase activity

• B-48 (240,000) found only in chylomicron
• lt5 mg derived from apo-B-100 gene by RNA
  editing lacks the LDL receptor-binding domain of
  apo-B-100

• B-100 (500,000) principal protein in LDL
• 80 100 mg binds to LDL receptor

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Apoproteins of human lipoproteins

• C-I (7,000) found in chylomicron, VLDL, HDL
• 4 7 mg may also activate LCAT
• C-II (8,800) - found in chylomicron, VLDL, HDL
• 3 8 mg activates lipoprotein lipase
• C-III (8,800) - found in chylomicron, VLDL, IDL,
  HDL
• 8 15 mg inhibits lipoprotein lipase

• D (32,500) - found in HDL
• 8 10 mg also called cholesterol ester
  transfer protein (CETP)

• E (34,100) - found in chylomicron, VLDL, IDL HDL
• 3 6 mg binds to LDL receptor

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Classification of Lipoproteins

• Based on Electrophoresis
• Paper chylo, beta, prebeta, alpha
• PAGE chylo, prebeta, beta, alpha
• Density in centrifugation
• chylomicrons
• very low density lipoproteins (VLDL)
• intermediate density lipoproteins (IDL)
• low density lipoproteins (LDL)
• high density lipoproteins (HDL)

Chylomicron remains at origin in electrophoretic
field
VLDL, IDL, Lpa in Prebeta
LDL, Beta
HDL, Alpha
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The five classes of lipoprotein(all contain
characteristic amounts TAG, cholesterol,
cholesterol esters, phospholipids and apoproteins)
Increasing density
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Composition and properties of human lipoproteins
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Isoprenoids
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Cholesterol Cholesterol is an essential
component of biomembranes and imparts stability
to the fluid structure. Cholesterol is a
steroid. All steroids have the same
basic structure consisting of 4 hydrocarbon rings
linked together Cholesterol has a OH group
which provides the polarity and a hydrocarbon
group at the other end which adds to its
hydrophobic nature In biomembranes, the OH of
cholesterol is aligned with the head group
(phosphate) of phospholipids Steroids are
important metabolically (cholesterol),
for digestion (bile salts), as hormones (human
sex hormones)
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Sphingolipids
PC
General Structure
Cer
Sm
GlcCb (neutral GL)
LacCer (Gb)
Gan
(i.e., blood groups)
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Phospholipids These are lipids that contain one
or more phosphate groups PL are the primary
components of biomembranes. Other lipids in
biomembranes are glycolipids and cholesterol.
Surfactants are phopsholipids, mostly
phosphatidylcholine PL are subclassified based
on their parent lipid phopshoglycerides or
sphingomyelins Phosphatidic acid basic
glycerophopholipid. 1,2- diacylglycerol joined to
phosphoric acid by an ester link. This phosphate
can form another ester linkage with an
alcohol. Serine phosphatidylserine Choline
phosphatidylcholine Ethanolamine
phosphatidylethanolamine Inositol phosphatidylin
ositol Glycerol diphosphatidylglycerol (cardioli
pin)
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Diglyceride esterified with phosphoric
acid which is bound as ester to
nitrogencontaining base or serine Named based on
nature of head Essential components of cell
membranes Align themselves between water phase
and lipid phase
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Phospholipids
Phospholipids (lecithin) Are composed of
Glycerol backbone 2 fatty acids Phosphate
Are partially soluble in water Are manufactured
in our bodies so they are not required in our diet
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Phospholipids ?? At least one fatty acid and one
phosphorus compound attached to glycerol ??
Includes lecithin (phosphotidylcholine)
and sphingomyelins ?? Synthesized by the body as
needed
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Functions of phospholipids ?? Are amphipathic so
can act as emulsifiers ?? Important component of
cell membranes ?? Present on the outer surface of
lipoproteins, allowing them to float freely in
the blood ?? Especially important for insulation
of nerves (in the myelin sheath as sphingomyelins)
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Sphingolipids
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Glycosphingolipids as determinants of
bloodgroups.
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Phospholipids
1- Glycerophospholipids 2-Sphingolipids

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Sphingolipids Sphingosine is a derivative of
glycerol but it has NH2 instead of -OH at C2 and
has a -OH as well as a long chain hydrocarbon on
C3 The NH2 forms an amide bond with a long
chain FA to form a ceramide. sphigomyelin is
formed when a phosphodiester bridge links the C1
-OH of ceramide to ethanolamine or choline
Sphingomyelins are found abundantly in the
myelin sheath that surrounds the nerve fibers
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Glycolipids Glycolipids are lipids that contain
carbohydrates Cerebrosides have a
monosaccharide attached to the C1 -OH of
ceramide Gangliosides have an oligosaccharide
attached to the C1 -OH of ceramide Cerebrosides
and gangliosides are found in the brain and
nervous tissue In biomembranes, glycolipids are
oriented asymmetrically with the sugar units
always on the extracellular side of the membrane
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Types of Fats (See figure 5-6) Saturated fats
are composed of triglycerides in which most
of the fatty acids are saturated. Saturated
fats are high in saturated fatty acids e.g.
beef, fat, cheese, milk fat, butter, etc.
Exceptions poultry and fish (less saturated)
Unsaturated fats Mono and polyunsaturated
fats. Most vegetable fats are high in
polyunsaturated fatty acids, e.g., corn oil,
safflower oil etc. Exceptions coconut oil,
palm oil. Coconut oil and palm oils are (also
called tropical oils) high in saturated fatty
acids.
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Hydrogenation of fatty acids ?? Process used to
solidify an oil to increase resistance to
oxidation, increase shelf-life
spreadability, increased smoke point ?? Addition
of H to CC double bonds ?? Formation of -trans
fatty acids
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Minimize intake of trans- fatty acids ?? Limit
use of processed grain products ?? Limit
deep-fried foods ?? Limit high fat baked goods ??
Limit use of non-dairy creamers ?? Ingredient to
watch for partially hydrogenated vegetable oil
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Olive and canola oils are high in monounsaturated
fatty acids. Fish oils are high in ?3 PUFA.
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Properties ?? melting points of
even-numberedcarbon fatty acids increase with
chain length and decrease according
to unsaturation ?? saturated, long-chain fatty
acids are solid at body temperature (high
melting point) ?? polyunsaturated fatty acids are
liquid at 0C (low melting point)
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Which Ones Are Essential? ?? Linoleic acid (182
?-6) ?? Alpha-Linolenic acid (183 ?-3) ??
Arachidonic acid (204 ?-6) (not?) ?? EPA (205
?-3) (most likely?) ?? DHA (226 ?-3) (most
likely)?
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?? Fatty acids can be saturated or
unsaturated ?? saturated fatty acids (SFA)
contain the maximum amount of hydrogens possible
- all C-C bonds are single ?? monounsaturated
fatty acids (MUFA) have 1 point of
unsaturation ?? polyunsaturated fatty acids
(PUFA) have 2 or more points of unsaturation ?? A
variety of the three fatty acids are found
in foods ?? Foods high in SFA tend to be solid at
room temperature, MUFA tend to be solid
at refrigerator temps, PUFA liquid at room
and refrigerator temps.
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Fatty Acids ?? Fatty acids are the simplest of
the lipids components of more complex lipids ??
Hydrocarbon chain with a methyl group at one end
and an acid group at the other end ?? Differ
from each other in chain length and degree of
saturation
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Sources ?? Generally, fats from fish
and vegetables are less saturated, fats from
animal products are more saturated.
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The Role of Fat
Essential fatty acids Two fatty acids cannot
be synthesized in the body and must be obtained
in the diet Alpha-linoleic acid (omega-3 fatty
acid) Found in canola oil, soybean oil, flax
seed and oil, some nuts Linoleic acid (omega-6
fatty acid) Found in green leafy vegetables,
vegetable oils and whole grains The Role of Fat
Essential fatty acids Three fatty acids can be
synthesized in the body but may have to be
obtained in the diet EPA and DHA (omega-3 fatty
acid) Found in oily fish and fish oil
supplements Arachidonic acid (omega-6 fatty
acid) Found in meats, dairy, eggs, and poultry
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The Role of Fat
Essential fatty acids Three fatty acids can
be synthesized in the body but may have to be
obtained in the diet EPA and DHA (omega-3 fatty
acid) Found in oily fish and fish oil
supplements Arachidonic acid (omega-6 fatty
acid) Found in meats, dairy, eggs, and poultry
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Essential Fatty Acids Cannot be synthesized in
the body, must be provided from the diet. Human
body cannot make Linoleic acid (182), Linolenic
acid (183). Humans do not have enzymes to make
any of the omega-6 or omega-3 fatty acids from
scratch, nor can they convert an omega-6 to
omega-3 fatty acid or vice versa. Because these
two fatty acids are indispensable to
body function, they must be supplied by the
diet. (Linoleic acid is omega 6 and Linolenic
acid is an omega 3 fatty acid).
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Omega 3 fatty acids The first double bond is on
C 3, counting from the methyl end of the fatty
acid. Ex. linolenic acid (183) Omega 6 fatty
acids The first double bond is on C
6, counting from the methyl end of the fatty
acid. Ex linoleic acid (182) The members of a
given family or series have different lengths and
different number of double bonds but the first
double bond occurs at the same point.
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Food Sources of Omega 3 Fatty Acids 1. Linolenic
acid 18 carbon and 3 double bonds (18 3) Ex
seeds, nuts, grains, soybeans, and veg. oils 2.
Eicosapentaenoic Acid (EPA) 20 carbons and 5
double bonds (205) Ex fish, shellfish 3.
Docosahexaenonic Acid (DHA) 22 carbons and 6
double bonds (226) Ex fish, shellfish
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Sources of Essential Fatty Acids ?? Vegetable
oils, meats, dairy, eggs - ?6 fatty acids
dominant ?? Marine and seafood, some
vegetable oils - ?3 fatty acids dominant
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Common fatty acids and shorthand
description Short chain 4-8 C, in milk
fat Butyric acid 40 Butanoic Medium chain
10-14 C, in coconut, palm kernel Lauric acid
120 Dodecanoic Typical 16-18 C, in plants and
animal Palmitic 160 hexadecanoic Stearic
180 octadecanoic Oleic 181 ?9 or 181 c9
octadecenoic Linoleic 182 ?6 or 182 c9, 12
octadecadienoic Linolenic 183 ?3 or 183 c9,
12, 15 octadecatrienoic Long chain 20-22 C, in
fish oil EPA 205 ?3 eicosapentaenoic DHA
226 ?3 docosahexaenoic
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Polyunsaturated Fatty Acids are Essential Fatty
Acids Linoleic (182?9,12) ?6 Linolenic
(183?9,12,15) ?3 Arachidonic (204?5,8,11,14) ?6
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Systematic naming of International Union of Pure
and Applied Chemistry (IUPAC) - ane gtgt -
anoic - ene gtgt - enoic - diene, triene,
tetraene gtgt - dienoic, - trienoic, tetraenoic
omega (?) counting from - CH3 end
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Chain length of fatty acids ?? Long chain FA gt
12 carbons ?? Medium chain FA 6 - 11 carbons ??
Short chain FA lt 6 carbons ?? can be released
directly from the intestinal cell into the blood
unlike longer chain fatty acids ?? Longer chain
fatty acids tend to be solid at room temperature
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Lehninger 343
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Molecular biology of the cell 239
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The degree of saturation of Fatty acids (a)
Saturated fatty acids carry maximum of H
atoms, and have no double bonds. Ex. Stearic acid
(18 carbons, no double bond or 180 ). Palmitic
acid has 16 Cs and no double bonds ( 160) (b)
Monounsaturated fatty acids lost 2 H atoms
and have one double bond. Ex. Oleic acid. 18 C,
one double bond ( 181) (c) Polyunsaturated fatty
acids(PUFA) two or more double bonds Ex.
Linoleic(18 carbons, 2 double bonds or 182) and
linolenic) acid (183).
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Rule of thumb for determining degree of
saturation for fats is How hard the lipid is
at room temperature. The more saturated a fat,
harder it is at room temperature. Vegetables
and fish oils are liquid at room temperature
(high in PUFA). Most animal fats are solid at
room temperature (high in saturated fatty acids)
e.g. beef fat, lard. Polyunsaturated fats have
lower melting point due to the carbon double
bonds.
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Rule of thumb for determining degree of
saturation for fats is How hard the lipid is
at room temperature. The more saturated a fat,
harder it is at room temperature. Vegetables
and fish oils are liquid at room temperature
(high in PUFA). Most animal fats are solid at
room temperature (high in saturated fatty acids)
e.g. beef fat, lard. Polyunsaturated fats have
lower melting point due to the carbon double
bonds.
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The Location of Double Bonds Poly unsaturated
fatty acids also differ in the location of double
bonds. There are two families of polyunsaturated
fatty acids These depend on the location of
first double bond counting from the methyl end of
the carbon chain. 1. Omega 3 (?3) 2. Omega 6
(?6 The Omega number indicates the position of
the first double bond in a fatty acid from the
methyl (CH3) end of the fatty acid.
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Triglycerides
Hydrogenation (Full and Partial) The addition
of hydrogen atoms to unsaturated fatty acids.
Coverts liquid fats (oils) into a more
solid form Used to create margarine from plant
oil Partial often creates trans unsaturated
fatty acids Full creates saturated fatty acids
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90 of dietary fat intake and 95 of
fat stored in tissues Plant sources high in
polyunsaturated fatty acids (oils) Animal
sources high in saturated fatty acids (fats)
Increased levels increased risk
for arteriosclerosis Indicated in blood by
creamy plasma layer
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Functions of triglycerides ?? In the body ??
Primary form of stored energy virtually
unlimited storage ?? adipose (fat) cells secrete
hormones and synthesizes enzymes that affect food
intake and energy use ?? why isnt glucose the
primary storage form of energy? ?? Provide fuel
for muscles during rest and light activity ??
Insulation against shock and temperature
extremes ?? Contain fat-soluble vitamins and
essential fatty acids
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Glycerophospholipids
General Structure
PA
Net Charge pH 7 -1
PC
PI45BP
Net Charge pH 7 0
Net Charge pH 7 -4