Title: LIPID STRUCTURE
1Lipid Structure
Reza Meshkani, PhD Department of
Biochemistry Faculty of Medicine Tehran
University of Medical Sciences
2Introduction
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
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4Lipids 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
5Lipid Components
Lipid Components
Fatty acids
Alcohol
Ester bandR1COOR2 Amid bandR1CONR2
Glycerol Phosphoglycerol Sterols Sphingosine
Saturated Unsaturated
6Fatty 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
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8Function 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
9Length 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)
10Nomenclature
- 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)
11Nomenclature
- 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)
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13Nomenclature
- 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
14Nomenclature
15Fatty 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
16? 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)
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18Palmitic 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.
19Arachidonic acid
- is present in the phospholipids
- involved in cellular signaling as a lipid second
messenger
20Why 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)
21Properties of Fatty acids
22Saponification
- Alkali hydrolysis of fatty acids
- R-COOH NaOH, KOH RCOONaH2O
23Isomeration
- 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)
24Hydrogenation
- 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.
25(No Transcript)
26Melting 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?
27Lipid 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)
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29Lipid 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
30Alcohol
31Glycerol is the basis of Triglyceride
Phosphoglycerol is basis of Phospholipids
32Sterol
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
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Sterols are basis of Cholesterol, Bile Acids,
Steroid hormones and Vitamin D
33Sphingosine
CH3-(CH2)12-CHCH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
34Classification of Lipids
35(No Transcript)
36Triglycerides
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
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38Triglycerides
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
39Phospholipids
40General Structure of Glycerophospholipid
41(No Transcript)
42X
Net Charge pH 7 -1
General Structure of glycerophospholipids
Phosphatidate
43Phosphatidyl 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
44Phosphatidylcholine
- 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.
45Therapeutic Uses
- Liver Disorders
- Detoxification
- Hypercholesterolemia and Atherosclerosis
- Manic depressive disorder
- Alzheimers Disease
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47Prostaglandines Leukoterines Tromboxane Prostacycl
ine
Arachidonic Acid
Phospholipase A2
- Lysolecithin
- At high concentration acts a Emulicification of
triglycerides
Phosphatidyl CholineLecithin
48Cholesterol ester
LCAT (Lecitin Cholesterol Acyl Transferase)
Fatty Acid
- Lysolecithin
- 7 of Plasma membrane PL
Phosphatidyl CholineLecithin
49Ether 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
50Phosphatidyl 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
51Phosphatidyl 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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53Phosphatidyl Glycerol
Net Charge pH 7 -1
54Cardiolipin
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
55Cardiolipin
- 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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57Clinical 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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59Phospholipases
PI45BP
60Indican 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.
61Sphingolipids
62Sphingosine
Sphingosine H Ceramide
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64SphingophospholipidSphingomyelin
Phosphocholine
- The most common sphingolipid
- Is found in Central nervous system and Myelin
membrane
65SphingoglycolipidCerebrosides
- Sphingosine Glucose Glucocerebroside (found
in RBC, WBC, Membrane) - Sphingosine Galactose Galactocerebroside
(found in Brain) - Galactocerebroside Sulfate Sulfatide
66GangliosidesComplex Cerebroside
GM1
O antigen
A antigen
B antigen
67Ganglioside
- 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
68Ganglioside 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
69Ganglioside nomenclature
- Numerical subscripts
- 1. Gal-GalNAc-Gal-Glc-ceramide
- 2. GalNAc-Gal-Glc-ceramide
- 3. Gal-Glc-ceramide
70A ganglioside (GM1)
71Gangliosidoses (Lipid Storage Diseases)
- Mutations in genes coding for enzymes of
ganglioside metabolism - Tay-sachs disease (deficiency of beta
galactosidase) - Sandhoff disease (Deficiency in hexoseaminidase)
72Waxes
73Steroids
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
74Cholesterol
- 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
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sitosterol-stigmastrol - ???? ?????? ?? ??????? ????????? ????????? ????
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76Cholesterol and cholesterol esters
77(No Transcript)
78Bile Acids
79Steroids Hormones
80(No Transcript)
81Progesterone
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
82Estradiol
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)
83Cortisole
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.
84Testosterone
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.).
85Aldosterone
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.
86Calcitriol
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.
87Vitamin 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
90Eicosanoid
- 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)
91SUBSTITUTION PATTERN OF PROSTANOIDS
92EICOSANOIDS
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.
93Eicosanoid Hormones
inhibited by glucocorticoids
inhibited by aspirin, ibuprofen
Or Cyclooxygenase (COX)
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????? - Ibuprofen ??? ???? ???? ??? ??? ????
????????????? ??? ??? ????? ??? ?????? ???? ???
???? ????? ?????
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
96Effects 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
97NSAIDs (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.
99Selective 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.
100Lipid 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 roleÂ
- Binding sites for receptorsÂ
- Activators or co-enzymes for enzymes involved
with lipid metabolismÂ
101(No Transcript)
102Physiological 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
103Functions 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
104Apoproteins 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
105Apoproteins 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
106Classification 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
107The five classes of lipoprotein(all contain
characteristic amounts TAG, cholesterol,
cholesterol esters, phospholipids and apoproteins)
Increasing density
108Composition and properties of human lipoproteins
109Isoprenoids
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112Cholesterol 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)
113Sphingolipids
PC
General Structure
Cer
Sm
GlcCb (neutral GL)
LacCer (Gb)
Gan
(i.e., blood groups)
114Phospholipids 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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116 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
117Phospholipids
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
118Phospholipids ?? At least one fatty acid and one
phosphorus compound attached to glycerol ??
Includes lecithin (phosphotidylcholine)
and sphingomyelins ?? Synthesized by the body as
needed
119Functions 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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122Sphingolipids
123Glycosphingolipids as determinants of
bloodgroups.
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125Phospholipids
1- Glycerophospholipids 2-Sphingolipids
126Sphingolipids 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
127Glycolipids 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
128Types 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.
129Hydrogenation 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
130Minimize 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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133Olive and canola oils are high in monounsaturated
fatty acids. Fish oils are high in ?3 PUFA.
134Properties ?? 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)
135Which 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)?
136?? 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.
137Fatty 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
138Sources ?? Generally, fats from fish
and vegetables are less saturated, fats from
animal products are more saturated.
139The 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
140The 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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143Essential 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).
144Omega 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.
145Food 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
146Sources of Essential Fatty Acids ?? Vegetable
oils, meats, dairy, eggs - ?6 fatty acids
dominant ?? Marine and seafood, some
vegetable oils - ?3 fatty acids dominant
147Common 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
148Polyunsaturated 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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150Systematic 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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153Chain 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
154Lehninger 343
155Molecular biology of the cell 239
156The 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).
157Rule 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.
158Rule 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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162The 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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167Triglycerides
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
168 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
169Functions 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
170Glycerophospholipids
General Structure
PA
Net Charge pH 7 -1
PC
PI45BP
Net Charge pH 7 0
Net Charge pH 7 -4