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LIPID CHEMISTRYCHEMISTRY & BIOLOGICAL MEMBRANES
LIPID CHEMISTRY & BIOLOGICAL MEMBRANES
Dolores V. Viliran, M.D.Dept of Biochemistry
•A diverse group of compounds that are related by A diverse group of compounds that are related by their insolubility in watertheir insolubility in water
•Soluble in non polar solvents such as ether, Soluble in non polar solvents such as ether, acetone, benzene and chloroformacetone, benzene and chloroform
•The bulk of lipid molecule is non polarThe bulk of lipid molecule is non polar
•There is no common subunit in their structureThere is no common subunit in their structure
•The primary building blocks in human lipids are fatty The primary building blocks in human lipids are fatty acids, glycerol, sphingosine and sterolsacids, glycerol, sphingosine and sterols
Introduction• LIPIDS
•A diverse group of compounds that are related by A diverse group of compounds that are related by their insolubility in watertheir insolubility in water
•Soluble in non polar solvents such as ether, Soluble in non polar solvents such as ether, acetone, benzene and chloroformacetone, benzene and chloroform
•The bulk of lipid molecule is non polarThe bulk of lipid molecule is non polar
•There is no common subunit in their structureThere is no common subunit in their structure
•The primary building blocks in human lipids are fatty The primary building blocks in human lipids are fatty acids, glycerol, sphingosine and sterolsacids, glycerol, sphingosine and sterols
• Energy source– 9 calories per gram
• Adipose → Fatty acids → CO2 + H2O + ATP
Major component of cell membrane
•Phosphoglycerides•Sphingolipids•Cholesterol
Specific functions of Lipids
2. Triglycerides Main storage form of fatty acids and chemical energy
3. Phospholipids Component of membranes; source of arachidonic acid,
Inositol triphosphate and diglyceride for signal transduction
4. 4. SphingolipidsSphingolipids Component of membranes Component of membranes
LIPIDLIPID FUNCTIONSFUNCTIONS
1. Fatty Acids1. Fatty Acids Metabolic fuelMetabolic fuel building blocks for other lipidsbuilding blocks for other lipids
5. Cholesterol5. Cholesterol Component of membranes, Component of membranes, precursor of bile salts and steroid precursor of bile salts and steroid hormoneshormones
Specific Functions of Lipids
6. Bile salts6. Bile salts Lipid digestion and absorption; main Lipid digestion and absorption; main product of cholesterol metabolismproduct of cholesterol metabolism
LIPID FUNCTION
7. Steroid 7. Steroid Intracellular signals that regulate gene Intracellular signals that regulate gene hormones hormones expression in target cellsexpression in target cells
8. Eicosanoids8. Eicosanoids Regulators of physiological functionsRegulators of physiological functions
9. Vitamins9. Vitamins Vision; calcium metabolism; Vision; calcium metabolism; antioxidants; blood coagulationantioxidants; blood coagulation
10. Ketone bodies10. Ketone bodies Metabolic fuelMetabolic fuel
Emulsification of Fats by Bile
Bile that is produced in the liver and stored in the gallbladder is releasedinto the Intestines for fat emulsification
BILEBILE
BILE
BILE
ENZYME
ENZYME ENZYME
BILE
BILE
BILE
BILE
VVV
BILE BILE BILEBILE
ENZYME ENZYME
ENZYME
ENZYME
BILE
BILEBILE
BILEB
ILE
BILE
BIL
E
BILE
BILEBILE
BILE
BILEBILE
BILEB
ILE
EMULSIFIED FATEMULSIFIED FAT
EMULSIFIED FAT
EN
ZY
ME
ENZYME
ENZYME
LIPID CLASSES
FATTY ACID DERIVATIVES
TRIACYLGLYCEROLS (TAG)
WAX ESTERS
PHOSPHOLIPDS
SPHINGOLIPIDS
ISOPRENOIDSo terpenes o steroids
LIPOPROTEINS
FATTY ACIDS AND THEIR DERIVATIVESFATTY ACIDS AND THEIR DERIVATIVES
OOH
RCOO- + H+RCOO- + H+R-COOHR-COOH
Fatty acids and their derivatives
Chemical formula
R-COOH = represents the alkyl chain composed of carbon and
hydrogen atoms
• Fatty acids are divided into: Short -- 2 to 4 arbon atoms Medium -- 6 to 10 arbon atoms Long -- 12 to 26 or more arbon atoms
• Human cells = long-chain variety• In nature fatty acids = even number of carbon atoms
R-COOHR-COOH RCOO- + H+RCOO- + H+
Fatty acids and their derivatives• Detergent properties
– The alkyl side chain seeks a nonpolar environment – carboxylate seeks an aqueous environment– The concentration of fatty acid in the circulation is
0.5 to 0.7 mM., and most of this fatty acid is bound to albumin
– Free fatty acids are not found as structural constituents of membranes
Saponification
DIRT
WATER
Saponification
DIRT
WATER
SURF DETERGENT
DETERGENT MOLECULES
Saponification
WATER
Saponification WATER
MICELLE
FATTY ACIDS
Names and Chemical Descriptions of some common Fatty acidsNames and Chemical Descriptions of some common Fatty acids
Saturated Fatty Acids• The fatty acids can be divided into two groups:
saturated and unsaturated. • Saturated fatty acidsSaturated fatty acids have only single bonds in
hydrocarbon chain. – Saturated fatty acids are solids at room temperature because
the regular nature of their aliphatic chains allows the molecules to be packed in close, parallel alignment:
The Interaction between neighboring chains are weak ,but the regular packing allows these forces to operate over a large portion of the chain so that considerable amount of energy is needed in order to melt them
Unsaturated Fatty Acids
• Unsaturated fatty acids have at least one C = C double bond in the chains.– In contrast, unsaturated fatty acids are all liquid at room
temperature because the cis double bonds interrupt the packing of the chains. Thus less energy is required to melt them. The greater the degree of unsaturation, the lower the melting point.
Unsaturated Fatty Acids
Double bonds in the cis form
1 double bond= monounsaturated
≥ 2 double bonds= polyunsaturated
Fish and plant fats have more polyunsaturated fatty acids than that of mammals or fowl
2 systems in designating location of double bonds; Based on lettering system,:
Δ (delta) system ω (omega) system
1 = carboxylate 1 = carboxylate
2 = 2 = -carbon-carbon
3 = 3 = -carbon -carbon methyl group = methyl group = -carbon-carbon
• Two systems are used to designate the position of double bonds
– In the ( delta ) system, • The carboxylate is considered as C1 • The position of the double bond is
denoted by the carbon atom of the double bond closest to the carboxylate
– In the n or -system, the methyl group is considered as C1.
PALMITATE 16:0
PALMITOLEATE 16:1; ω-7
LINOLEATE 16:1; ω-6
COOH
COOH
Fatty Acid NomenclatureDescriptive Numeric Δ n ω
Name
PALMITATE 16:0
PALMITOLEATEPALMITOLEATE 9-16:1 9-16:1 16:116:1ΔΔ99 16:1n-7 16:1 16:1n-7 16:1ωω-7-7
LINOLEATE LINOLEATE 9,12-18:2 18:2 9,12-18:2 18:2 ΔΔ9,12 19,12 1 8:2n-6 8:2 8:2n-6 8:2 ωω-6-6
LINOLENATELINOLENATE 9,12,15-18:3 18:3 9,12,15-18:3 18:3 ΔΔ9,12,15 18:3n-3 18:39,12,15 18:3n-3 18:3ωω-3-3
CIS and TRANS ISOMERISM• Occurrence
Cis double bonds• in humans, other animals, plants and bacteria
Trans double bonds- Catalytic hydrogenation of vegetable oils
- Margarine, cookies, candies, fried foods
↑ double bonds= ↓ melting point-Liquid at room temperature
↓ double bonds= ↑ melting point-Solid at room temperature
Trans fatty acids do not accumulate in human Trans fatty acids do not accumulate in human tissues, and cells contain enzyme activities tissues, and cells contain enzyme activities required required to completely oxidize such nutrients.to completely oxidize such nutrients.
ESSENTAL FATTY ACIDS
-- body can synthesize needed fat body can synthesize needed fat except:except:
- linoleic and alpha-linolenic acid- linoleic and alpha-linolenic acid
-- body cannot add double bonds 9 body cannot add double bonds 9 carbons from deltacarbons from delta end end
-- not form w-3 and w-6not form w-3 and w-6- - form w-9 onlyform w-9 only
ESSENTAIL FATTY ACIDS
OMEGA 3 FAMILY
OMEGA 6 FAMILY
OMEGA 6 FAMILY
ESSENTIAL FATTY ACIDS
w-3 & w-6 family are produced w-3 & w-6 family are produced from from essential fatty acidsessential fatty acids
w-3 family from alpha-linolenic acidw-3 family from alpha-linolenic acid
- w-6 family from linoleic acid- w-6 family from linoleic acid
by ELONGASEby ELONGASE – add C atoms in pairs at delta end – add C atoms in pairs at delta end
by DESATURASEby DESATURASE – form double bond – form double bond
Production of Essential fatty acid derivatives
ESSENTIAL FATTY ACIDS• Polyunsaturated, or polyenoic fatty acids
linoleic acid (C18) having two double bond
linolenic acid (C18) having three
arachidonic acid (C20) having four double bonds
ESSENTAIL FATTY ACIDS
Linoleic acid (Linoleic acid (-6 class) and -6 class) and linolenic acid (linolenic acid (-3 class) are -3 class) are termed essential fatty acids termed essential fatty acids because they cannot be because they cannot be synthesized in mammalssynthesized in mammals
REMEMBER:
Linoleic acid can be converted Linoleic acid can be converted to to -linolenic acid and -linolenic acid and Arachidonic acid can be formed Arachidonic acid can be formed from linoleic in most mammals from linoleic in most mammals
The true essential fatty acid is Linoleic acid.The true essential fatty acid is Linoleic acid.
ESSENTIAL FATTY ACIDS
ARACHIDONIC ACID
A 20 – carbon Omega 6 Fatty acid with 4 double bonds
Give rise to Eicosanoids
prostaglandins, prostaglandins,
thromboxanes, thromboxanes,
lipoxins and lipoxins and
leukotrienesleukotrienes
Biological Actions of Selected Eicosanoid Molecules
ARACHIDONIC ACID
Leukotrienes
LIPOOXYGENASE
CYCLOOXYGENASE
TxA2PGH2
PGIAnti-platelet aggregation
Vasodilatation
Platelet aggregation
Vasoconstriction
PGE2 PGF2α
Smooth muscle contraction
Vasodilatation
Smooth muscle contraction
Vasoconstriction
InflammationsBronchoconstrictions
VasoconstrictionCapillary Permeability
ESSENTIAL FATTY ACIDSESSENTIAL FATTY ACIDS
EICOSANOIDSEICOSANOIDS
- 20 carbon substances- 20 carbon substances- - prostaglandinsprostaglandins – in prostate – in prostate glandgland- - thromboxanethromboxane – in – in thrombocytesthrombocytes- - leucotrienesleucotrienes – in leucocytes– in leucocytes
- - like hormoneslike hormones
- - in inflammation, clotting, in inflammation, clotting, and immune responseand immune response
EICOSANOIDSEICOSANOIDS
EICOSANOIDS
TRIACYLGLYCEROLS (TAG)• The main storage forms of fatty acids• The acylglycerols are esters of fatty acids bound to
the sugar alcohol glycerol
CH2
CH
CH2
O
O
O
O
O
O
C-(CH2)12
C-(CH2)7
C-(CH2)16
CH3
CH3
CH=CH- (CH2)7-CH3
MYRISTIC ACID
OLEIC ACID
STEARIC ACID
TAG
• Such Compounds are called Triglycerides or Triacyglycerides: All three OH groups of Glycerol are Esterified
• They Are the most common Lipid Material, although Mono- and Diglycerides are not infrequent; in the latter two types, only one or two OH groups of Glycerol are esterified by Fatty Acids
• They are Complex Mixtures; although some molecules have 3 identical fatty acids, in most cases 2 or 3 different FA are present.
TAG
• They are also called neutral fats, because the carboxyl groups of the fatty acids are bound in ester linkage and can no longer function as acids. The fatty acid moiety in lipid esters is known as an acyl group.
• TAG mixtures are referred to as fats or oils
– Fats= which are solid at room temperature, contain a large proportion of saturated fatty acids
– Oils = are liquid at room temperature because of their relatively high unsaturated fatty acid content
AGENERAL TYPES of TAG
TRIACYLGLYCEROL
CH2 – O – C – R1
O
HC - OH
CH2OHMAG
CH2 – O – C – R1
HC – O – C – R2
CH2OH
O
O
DAG
CH2 – O – C – R1
O
O
HC – O – C – R2
CH2O – O – C – R3
O
TAG
MAG DAG TAG
TAG• In humans
– Hydrolyzed by lipase to glycerol + FFA • In industry
– Hydrolyzed by NaOH to create glycerol + water-soluble soaps
• In animals– Major storage and transport form of FA– Insulation in low temperatures– Makes fur and feathers water-repellent
• In plants– Energy reserve in fruits and seeds
WAX ESTERS• Waxes are complex mixtures of nonpolar lipids• They are protective coatings on leaves, stems, and
fruit of plants and the skin and fur of animals• Esters composed of long-chain fatty acids and long-
chain alcohols are prominent constituents of most waxes
• Well-known examples of waxes include carnauba wax, produced by the leaves of the Brazilian wax palm, and beeswax– The predominant constituent of carnauba wax is the wax
ester melissyl cerotate. Triacontyl hexadecanoate is one of several important wax esters in beeswax
• Waxes also contain hydrocarbons, alcohols, fatty acids, aldehydes and sterols ( steroid alcohols).
COMPLEX LIPDS
SCEMATIC DIAGRAM OF SIMPLE AND COMPLEX LIPDS
SIMPLE AND COMPLEX LIPIDS
SIMPLECOMPLEX
PHOSPHOLIPIDS GLYCOLIPIDS
PHOSPHOGLYCERIDES SPHINGOLIPIDS
GL
YC
ER
OL
FA
FA
PO4
FA
PO4ALCOHOL ALCOHOLS
PH
ING
OS
INE
• Phosphoglyceride molecules are classified according to which alcohol becomes esterified to the phosphate group– Phosphatidylcholine (PC or Lecithin) =
• the alcohol is choline
– phosphatidylethanoalmine (PE) = • ethanolamime
– Phosphatidylserine (PS) = • serine
– diphosphatidylglycerol (dPG) = • phosphatidylyglycerol
– phosphatidylinositol (PI) = • Inositol
•A derivative of A derivative of phosphatidylinositol,phosphatidylinositol, namely namely phosphatidyl-4,5-bisphosphate (PIP2), is found phosphatidyl-4,5-bisphosphate (PIP2), is found in only small amounts in plasma membranes.in only small amounts in plasma membranes.
• PIP2 is now recognized as an important component PIP2 is now recognized as an important component of a second messenger systemof a second messenger system
•The most common fatty acids in the phosphoglycerides The most common fatty acids in the phosphoglycerides have between 16 and 20 carbonshave between 16 and 20 carbons
•Saturated fatty acids usually occur at C-1 of glycerolSaturated fatty acids usually occur at C-1 of glycerolThe fatty acid substituent at C-2 is usually unsaturatedThe fatty acid substituent at C-2 is usually unsaturated
Phospholipids• Contains an alcohol, Fatty acid and a
phosphate group.• There are two types:
– Glycerophospholipids ( phosphoglycerides)– Sphingolipids( sphingomyelins)
In glycerophospholipids, the alcohol is glycerol
In Sphingolipds, the alcohol is sphingosine
Phospholipids
PHOSPATIDYLSERINEPHOSPHATIDYLETHANOLAMINEPHOSPHATIDYLCHOLINE
Biological importance of Phospholipids
• Lecithin or phosphatidylcholines or surfactants or surface-acting agents– play an essential role in reducing surface tension
in lung alveoli; they are– Increase Pulmonary Compliance is usually seen in
this disease where alveoli (in the Lungs) are collapse due to strong surface Tension secondary to reduced or absence of surfactants- usually fatal.
– Respiratory distress syndrome (RDS) of the newborn, which is common in premature infants, results from a lack of this surfactant in the lung
Biological importance of Phospholipids
To predict the likelihood of RDS in high-risk pregnancies, obstetricians commonly perform amniocentesis for laboratory determination of the ratio of phosphatidylcholine (lecithin) to sphingomyelin in the amniotic fluid
(L/S ratio)
The higher the L/S ratio, the more surfactant is present to allow the lung to expand normally
The major features of the lungs include the bronchi, the bronchioles and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.
• Hyaline membrane disease (Neonatal Respiratory Distress Syndrome - NRDS) is characterized by collapsed alveoli alternating with hyperaerated alveoli, vascular congestion and hyaline membranes (resulted from fibrin, cellular debris, red blood cells, neutrophils and macrophages). Hyaline membranes appear like an eosinophilic, amorphous material, lining or filling the alveolar spaces and blocking the gases exchange.
Biological importance of Phospholipids
• Serologic test for syphilis, the Venereal Disease Research Laboratory (VDRL) test, utilizes cardiolipin, a diphosphatidyl glycerol as the antigen
• The highly polar phosphate, choline, and serine
groups of the phosphoglycerides make these compounds water-soluble, while their fatty acyl groups confer solubility in nonpolar agents
– Hence, they can serve to cement lipids to membranes and lipoproteins to the polar proteins and carbohydrates.
SPHINGOLIPIDS
• The Sphingolipids contain sphingosine as their amino alcohol • There are three general classes of Sphingolipids:
a) Sphingomyelin
b) Cerebrosides
c) gangliosides
substituent attached to the C1-hydroxyl group of sphingosine separates these three classes:
Sphingomyelin contains phosphocholine Cerebrosides contain a monosaccharide Gangliosides contain an oligosaccharide
CERAMIDE- Plays an important role in the formation of these 3 classes .
SPHINGOLIPIDS
CERAMIDESCERAMIDES•consist of a fatty acid bound to sphingosineconsist of a fatty acid bound to sphingosine
•In humans, ceramides function principally as In humans, ceramides function principally as intermediates in the synthesis of other sphingolipidsintermediates in the synthesis of other sphingolipids
SPHINGOMYELINSPHINGOMYELIN •By joining choline phosphate or ethanolamine By joining choline phosphate or ethanolamine phosphate to ceramides, one generates the phosphate to ceramides, one generates the sphingomyelin.sphingomyelin.. important components of the myelin sheath . important components of the myelin sheath surrounding the fastest conducting fiber.surrounding the fastest conducting fiber.
CEREBROSIDESCEREBROSIDES•They consist of a hexose sugar, such as glucose They consist of a hexose sugar, such as glucose or galactose, bound to a ceramide.or galactose, bound to a ceramide.
•These ceramide-monosaccharides are also part of These ceramide-monosaccharides are also part of the myelin sheath.the myelin sheath.
SPHINGOLIPIDS
GANGLIOSIDESGANGLIOSIDES •Consist of ceramide bound to an oligosaccharide Consist of ceramide bound to an oligosaccharide that contains an acidic sugar such as N-that contains an acidic sugar such as N-acetylneuraminic acidacetylneuraminic acid
SULFATIDESSULFATIDES• Are sulfated cerebrosides, or cerebroside-sulfate esters.Are sulfated cerebrosides, or cerebroside-sulfate esters.
The coating of nerve axons (myelin) contains a different kind of complex lipid called sphingolipids. In sphingolipids the alcohol portion is sphingosine: NONE CONTAINS GLYCEROLNONE CONTAINS GLYCEROL
ISOPRENOIDS• With repeating 5-carbon units (isoprene)• Types: terpenes and steroids• TERPENES
– Monoterpenes 2 isoprene units• Geraniol in oil of geranium
– Sesquiterpenes 3 isoprene units• Farnesene in oil of citronella
– Diterpenes 4 isoprene units• Phytol, a plant alcohol• Squalene, in shark liver oil
– Triterpenes 6 isoprene units• Olive oil and yeast
– Tetraterpenes 8 isoprene units• Carotenoids
– Polyterpenes bet. 3,000 and 6,000 units• Natural rubber
• Mixed Terpenoids – Several important biomolecules are composed of
nonterpene components attached to isoprenoid groups (often referred to as prenyl or isoprenyl groups)
– Examples of these biomolecules, referred to as mixed terpenoids, include vitamin E ( α-tocopherol), ubiquinone, vitamin K and some cytokinins ( plant hormones)
STEROIDS
• The third major class of lipids is the steroids, which are compounds containing this ring system
• There are three cyclohexane rings (A,B, C) connected in the same way as in phenanthrene and a fused cyclopentane ring (D).
• Steroids are thus completely different in structure from the lipids.
STEROIDS– Complex derivatives of triterpenes– All with 4 fused rings– Distinguished by placement of C-C double bonds
and other substituents (hydroxyl, carboxyl, alkyl) The essential structural nucleus of the steroids
consists of three fused cyclohexane rings (A-C) joined to a cyclopentene ring (D)
They are found in all eukaryotes and a small number of bacteria
Cholesterol, an important molecule in animals, is an Cholesterol, an important molecule in animals, is an example of the steroids. In addition to being an example of the steroids. In addition to being an essential component in animal cell membranes, essential component in animal cell membranes, cholesterol is a precursor in the biosynthesis of all cholesterol is a precursor in the biosynthesis of all steroid hormones, vitamin D, and bile saltssteroid hormones, vitamin D, and bile salts
Animal Steroids
cholesteroL Free cholesterol
testosterone estradiol (estrogen) Progesterone
CHOLESTEROL
HO
CH3
CH3
CHOLESTEROL
Cholesterol in Selected Foods
STEROIDSEstrogensEstrogens= “OVARIAN STEROID”= “OVARIAN STEROID”
Contain 18 carbon atoms (Carbon 18 is found in a methyl Contain 18 carbon atoms (Carbon 18 is found in a methyl group)group)
Unlike other steroids, the A ring of the steroid nucleus of Unlike other steroids, the A ring of the steroid nucleus of estrogen is aromatic. estrogen is aromatic.
EstradiolEstradiol has OH groups attached to has OH groups attached to carbons 3 and.17.carbons 3 and.17.
• Androgens,Androgens,• This Steroid is produced in the adrenal cortex and the This Steroid is produced in the adrenal cortex and the
testestestes• Having19 carbon atoms (Carbons 18 and 19 are in methyl Having19 carbon atoms (Carbons 18 and 19 are in methyl
groups)groups)• Testosterone is one of the more potent androgenTestosterone is one of the more potent androgen• Dehydroepiandrosterone (DHA), unlike testosterone, is a Dehydroepiandrosterone (DHA), unlike testosterone, is a
17-ketosteroid17-ketosteroid
Animal Steroids
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
A
C
B
D
CHOLESTEROL FREE CHOLESTEROL
HO
O
OH
TESTOSTERONE
HO
OH
ESTROGEN
OH
O
O
PROGESTERONE
STEROIDS
• Progesterone= synthesized in the corpus luteum, has 21 carbons, as do the adrenocortical steroids such as corticosterone and cortisol– Progesterone has an acetyl group joined at
carbon 17
• The bile acids are 24-carbon steroids secreted into the bile to emulsify dietary fats– They have a five-carbon side chain at position 17
that contains a carboxyl group, making them acidic
– Cholic acid is a major human bile acid
STEROIDS
•The adrenal cortex produces glucocorticoids, which The adrenal cortex produces glucocorticoids, which raise the serum glucose level, and mineralocorticoids, raise the serum glucose level, and mineralocorticoids, which promote renal sodium retentionwhich promote renal sodium retention
•Cortisol is a potent glucocorticoid with weak Cortisol is a potent glucocorticoid with weak mineralocorticoid activity, whereas aldosterone is mineralocorticoid activity, whereas aldosterone is a potent mineralocorticoid (presumably due to its a potent mineralocorticoid (presumably due to its aldehyde group at carbon 18) but a weak aldehyde group at carbon 18) but a weak glucocorticoidglucocorticoid
A hydroxyl or keto group at carbon 11 is found A hydroxyl or keto group at carbon 11 is found to correlate with glucocorticoid activityto correlate with glucocorticoid activityThe urinary 17-hydroxycorticosteroid assay The urinary 17-hydroxycorticosteroid assay detects all 21-carbon steroids with a 17-OH detects all 21-carbon steroids with a 17-OH group, such as cortisolgroup, such as cortisol
LIPOPROTEINS
• Lipids must bind to proteins to make them water-soluble for transport in the blood
• Free fatty acids, for example, avidly bind to serum albumin and will displace albumin-bound drugs from their binding sites.
• Two laboratory techniques are used to separate lipoproteins from one another:– ultracentrifugation separates them according to their
• differing densities
– electrophoresis separates them on a basis of their varying • net charges
LIPOPROTEINS
Each type of lipoprotein contains a neutral lipid core composed of Cholesterol esters and TAG The core is sorrounded by a layer of Phospholipid, free cholesterol and proteinCharged and polar residues on the surface of a lipoprotein enable it to dissolve in blood
LIPOPROTEINS
Chylomicrons
• Chylomicrons are the least dense lipoproteins, because consist mainly of triglycerides with small amounts of cholesterol, phospholipids, and proteins
• They do not migrate when subjected to electrophoresis, because their high triglyceride content (triacylglycerols have no charge)
• After a fatty meal, the blood appears milky due to the high concentration of chylomicrons
• Lipoprotein lipase hydrolyzes triglycerides bound in lipoproteins such as chylomicrons and VLDL, yielding monoglycerides and free fatty acids
CHYLOMICRONS
– Heparin, an anticoagulant, also helps to clear chylomicrons from the blood, perhaps by stimulating lipoprotein lipase
– The inherited absence of lipoprotein lipase causes hyperchylomicronemia, termed Frederickson‘s type 1 hyperlipoproteinemia.
Very low-density lipoproteins (VLDL)
• Very low-density lipoproteins (VLDL) also contain principally triglycerides, but have a greater protein, phospholipid, and cholesterol content than chylomicrons
• Their protein and phospholipid content makes them charged so that they migrate just before the B-globulins in electrophoresis; hence, they are termed pre-B Lipoproteins
• VLDL is synthesized in the liver• This VLDL fraction is markedly elevated in type IV
hyperlipoproteinemia.
Low-density lipoproteins (LDL)
• Low-density lipoproteins (LDL) contain mainly cholesterol, in contrast to the content of chylomicrons and VLDL, which is mainly triglyceride
• LDL also contains appreciable amounts of proteins, phospholipids, and triglycerides. Because they migrate together with the β-globulins, they are termed β-lipoproteins
• The LDL fraction is markedly elevated in type II hyperlipoproteinemia and is associated with a high incidence of atherosclerosis.
High-density lipoproteins (HDL)
• High-density lipoproteins (HDL) contain mainly protein and phospholipid
• They contain significant amounts of cholesterol, but have little triglyceride
• The high protein, low triglyceride content makes them very dense
• They are termed alpha-Lipoproteins and are separated from other lipoproteins by electrophoresis.
BIOLOGICAL MEMBRANE
• Biological membranes are thin sheet-like structures composed mainly of lipid and protein
• Membrane lipids create the permeability barrier, while membrane proteins serve as pumps, enzymes, receptors, and energy transducers
• Membranes create compartments ranging from mitochondria and nuclei to cells.
• Three main classes of lipids are found in biological membranes: – Phospholipids
– glycolipids
– Cholesterol
Biological Membrane
• The phospholipids are based on either glycerol or sphingosine
– Glycerol-based phospholipids include phosphatidyl choline, phosphatidyl inositol, and phosphatidyl ethanolamine
– Sphimgomyelin is one of the sphingosine-based phospholipids
– Membrane glycolipids include cerebrosides and Gangliosides
Biological Membrane
Non-polar
PolarA PHOSPHOLIPID BILAYER
EXTRACELLULAR MEMBRANE PROTEIN
TRANS-MEMBRANE PROTEIN
INTRACELLULAR MEMBRANE PROTEIN
MEMBRANE PROTEINS EMBEDDED IN PHOSPHOLIPID BILAYER
Biolological Membrane
BIOLOGICAL MEMBRANE
• The purpose of the membrane is to separate cells from the external environment and to provide selective transport for nutrients and waste products. That is, membranes allow the selective passage of substances into and out of the cells.
• The cell membrane is made up of lipid bilayers. In a lipid bilayer there are two layers of lipid molecules arranged tail to tail. The hydrophobic tails point toward each other because that enables them to get as far away from the water as possible. This leaves the hydrophilic heads projecting to the inner and outer surfaces of the membrane.
BIOLOGICAL MEMBRANESMembrane Lipid Hydrophobic Unit Hydrophilic Unit
Phosphoglycerides Fatty acid side chains Phosphorylated alcohol
Sphingomyelin Fatty acid chain & hydrocarbon chain of sphingosine
Phosphoryl choline
Glycolipid Fatty acid chain & hydrocarbon chain of sphingosine
One or more sugar residue
Cholesterol Entire molecule except OH group
OH group of C-3
Lipid Bilayer
• Amphipathic– Hydrophilic:
“water-loving” polar head group
– Hydrophobic: “water-hating” non-polar tails
The Lipid Bilayer Forms the Membrane Structure
Before there was the Fluid Mosaic Model...
• 1895: Charles Overton– membranes are made of lipids
• 1917: Irving Langmuir– model looks like a half of the lipid bilayer
• 1925: Gorter and Grendel – cell membranes must actually be phospholipid bilayers, two
molecules thick
• 1935: Davson and Danielli – sandwich model(Campbell, 2002)
Fluid Mosaic Model (Singer and Nicolson, 1972)
The cell membrane is a mosaic of protein molecules bobbing in a fluid bilayer of phospholipids.
What makes up the cell membrane?
Lipids Proteins Carbohydrates
LIPIDS
• phospholipids, glycosphingolipids and sterols
• insoluble in water • form the cell membrane • lipid-soluble substances (i.e.
O2, CO2, steroid hormones)
readily cross the cell membrane
Phospholipids
Phosphoglycerides have glycerol backbone
Myelin, a type of sphingomyelin has a sphingosine backbone
Cholesterol
• Most common sterol in membranes
• Generally more abundant toward the outside of the plasma membrane
• Intercalates among phospholipids
(Murray et al., 1996)
Cholesterol and Membrane Fluidity
Temperature and Membrane Fluidity
• ..cell membrane\membrane_structure.mov• ..active_transport_1.mov• ..diffusion.mov• ..Exocyt and Endo Anim.mov
COMPOSITION OF DIETARY FATS
• Mixture or fatty acid derivatives• Fats from animals have more saturated fats
than from plants• Saturated FA ↑ HDL, ↑ LDL
• Mono-UFA↑ HDL, ↓ LDL
• PUFA maintains HDL, ↓ LDL
• Trans FA ↓ HDL, ↑ LDL
COMPOSITION OF DIETARY FATS
• Treatment of hypercholesterolemia– Diets that contain MUFA and PUFA
• Treatment of hypertriglyceridemia and protection against thrombosis– ω-3 class of PUFA
• Produced by plants that grow in cold sea water. Fish such as salmon feed on this vegetation
COMPOSITION OF DIETARY FATSPALMITIC (C-16-
0)STEARIC
(C-18-0)
OLEIC
(C-18:1)
LINOLEIC
(C-18:2)
α-LINOLENIC
(C-18:3)
Perilla oil 6 2 17 15 61
Flaxseed oil 3 7 21 16 53
Manhattan Herring oil 19 4 13 1 1
Canola oil 5 2 53 22 10
Walnut oil 7 2 50 16 10
Soybean oil 11 4 23 51 7
Butter/milkfat 25 11 26 2 2
Beef fat 29 20 42 2 0
Palm oil 45 5 38 10 0
Olive oil 14 3 71 10 0
Corn oil 11 2 25 55 0
Sunflower seed oil 6 4 24 65 0
Borage seed oil 11 4 16 39 0
Evening primrose oil 6 1 11 72 1
Safflower seed oil 7 3 15 75 0
LIPID PEROXIDATION• Peroxidation- exposure of lipids to O2
– Causes deterioration of food (rancidity)– May cause tissue damage leading to cancer, inflammatory
diseases, atherosclerosis, aging, etc.
• The deleterious effects are initiated by free radicals (Ko, KOo, KOOo, OHo) produced during peroxide formation from fatty acids containing methylene-interrupted double bonds, such as those found in naturally-occuring PUFA
• Chain reaction producing continuous supply of free radicals that initiate peroxidation
LIPID PEROXIDATION• Initiation• ROOH + metal (n+1) → ROO0+
metal (n-1)• RH + X → R0 + XH
• Propagation• R0 + O2 → ROOH• ROO0 + RH → ROOH + R0, etc
• Termination• ROO0 + ROO0 → ROOR + O2• ROO0 + R0 → ROOR• R0 + R0 → RR
Classes Of Antioxidants • Preventive antioxidants
– Reduce the rate of chain initiation– Examples
• Catalase• Chelators of metal ions
– DTPA (diethylenetriaminepentaacetate)– EDTA (ethylenediaminetetraacetate)
• Chain-breaking antioxidants– Interfere with chain propagation– Examples
• Phenols• Aromatic amines
• In vivo, superoxide dismutase which acts on aqueous phase to trap superoxide free radicals (O-o)
• Peroxidation is also catalyzed by heme compounds and by lipooxygenases found in platelets and leukocytes
Separation & Analysis of Lipids
• Thin layer chromatography
• Gas-liquid chromatography
• Saponification
• Salting out method
Amphipathic Lipids
• Self-orient at oil-water interfaces
• Form membranes, micelles, liposomes, emulsions
• Amphipathic
– Hydrophobic- water-insoluble
– Hydrophilic water soluble
Amphipathic LIpids
• Oriented at oil-water interface with polar at water phase, non-polar at oil phase– Biologic membrane
• lipid bilayer– Micelles
• polar lipids in an aqueous solution or medium– Liposomes
• lipid bilayer forming a vesicle by sonicating an amphipathic lipid
• serves as cancer drugs– Receptors
• tissue-specific antibodies– Emulsions
• larger particles, formed by non-polar lipids in an aqueous medium stabilized by emulsifying agents such as polar lipids (lecithin)
