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Introduction
LIPIDS A diverse group of compounds that are related by A diverse group of compounds that are related by their insolubility in water their insolubility in water Soluble in non polar solvents such as ether, Soluble in non polar solvents such as ether, acetone, benzene and chloroform acetone, benzene and chloroform The bulk of lipid molecule is non polar The bulk of lipid molecule is non polar There is no common subunit in their structure There 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 sterols acids, glycerol, sphingosine and sterols
Energy source
9 calories per gram
1. Fatty Acids
2. Triglycerides 3. Phospholipids
4. Sphingolipids 5. Cholesterol
9. Vitamins
Metabolic fuel
Bile that is produced in the liver and stored in the gallbladder is released into the Intestines for fat emulsification
VVV
ENZYME
BILE
EMULSIFIED FAT
BILE
LIPID CLASSES
FATTY ACID DERIVATIVES TRIACYLGLYCEROLS (TAG)
WAX ESTERS
PHOSPHOLIPDS
SPHINGOLIPIDS
ISOPRENOIDS o terpenes o steroids LIPOPROTEINS
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-COOH
RCOO- + H+
Saponification
WATER
DIRT
Saponification
SURF DETERGENT
WATER
DETERGENT MOLECULES
DIRT
Saponification
WATER
Saponification
WATER
MICELLE
FATTY ACIDS
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,: (delta) system (omega) system 1 = carboxylate
2 = -carbon
3 = -carbon methyl group = -carbon
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; -7
LINOLEATE 16:1; -6
COOH
16:0 9-16:1 9,12-18:2 16:19 18:2 9,12 1 16:1n-7 8:2n-6 16:1-7 8:2 -6
LINOLENATE
9,12,15-18:3
18:3 9,12,15
18:3n-3
18:3-3
OMEGA 3 FAMILY
OMEGA 6 FAMILY
OMEGA 6 FAMILY
Linoleic acid (-6 class) and linolenic acid (-3 class) are termed essential fatty acids because they cannot be synthesized in mammals Linoleic acid can be converted to -linolenic acid and Arachidonic acid can be formed from linoleic in most mammals The true essential fatty acid is Linoleic acid.
lipoxins and
leukotrienes
Leukotrienes
Vasodilatation
PGI
PGH2
TxA2
Platelet aggregation Vasoconstriction
Anti-platelet aggregation
PGE2
Smooth muscle contraction Vasodilatation
PGF2
Smooth muscle contraction Vasoconstriction
Inflammations
- 20 carbon substances
EICOSANOIDS
TRIACYLGLYCEROLS (TAG)
The main storage forms of fatty acids The acylglycerols are esters of fatty acids bound to the sugar alcohol glycerol O CH2 O C-(CH2)12 CH3 O C-(CH2)7
MYRISTIC ACID
CH
CH=CH- (CH2)7-CH3
OLEIC ACID
CH2
C-(CH2)16 CH3 O
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
MAG
DAG
TAG
TRIACYLGLYCEROL
TAG
In humans Hydrolyzed by lipase to glycerol + FFA In industry Hydrolyzed by NaOH to create glycerol + watersoluble 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 longchain 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
SIMPLE
COMPLEX
PHOSPHOLIPIDS
GLYCOLIPIDS
PHOSPHOGLYCERIDES
FA GLYCEROL FA ALCOHOL
SPHINGOLIPIDS
SPHINGOSINE FA
PO4
PO4
ALCOHOL
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 phosphatidylinositol, namely phosphatidyl-4,5-bisphosphate (PIP2), is found in only small amounts in plasma membranes. PIP2 is now recognized as an important component of a second messenger system
The most common fatty acids in the phosphoglycerides have between 16 and 20 carbons Saturated fatty acids usually occur at C-1 of glycerol The 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
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.
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
CERAMIDES consist of a fatty acid bound to sphingosine In humans, ceramides function principally as intermediates in the synthesis of other sphingolipids SPHINGOMYELIN By joining choline phosphate or ethanolamine phosphate to ceramides, one generates the sphingomyelin. . important components of the myelin sheath surrounding the fastest conducting fiber. CEREBROSIDES They consist of a hexose sugar, such as glucose or galactose, bound to a ceramide. These ceramide-monosaccharides are also part of the myelin sheath.
SPHINGOLIPIDS
GANGLIOSIDES
Consist of ceramide bound to an oligosaccharide that contains an acidic sugar such as Nacetylneuraminic acid
The coating of nerve axons (myelin) contains a different kind of complex lipid called sphingolipids. In sphingolipids the alcohol portion is sphingosine: NONE CONTAINS GLYCEROL
ISOPRENOIDS
With repeating 5-carbon units (isoprene) Types: terpenes and steroids TERPENES
Monoterpenes
Geraniol in oil of geranium
Sesquiterpenes
Farnesene in oil of citronella
Diterpenes
Phytol, a plant alcohol Squalene, in shark liver oil
4 isoprene units
Triterpenes
Olive oil and yeast
Tetraterpenes
Carotenoids
Polyterpenes
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 ( -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 example of the steroids. In addition to being an essential component in animal cell membranes, cholesterol is a precursor in the biosynthesis of all steroid hormones, vitamin D, and bile salts
Animal Steroids
cholesteroL
Free cholesterol
testosterone
estradiol (estrogen)
Progesterone
CHOLESTEROL
CH3 CH3 HO
CHOLESTEROL
STEROIDS
Estrogens= OVARIAN STEROID
Contain 18 carbon atoms (Carbon 18 is found in a methyl
group)
Unlike other steroids, the A ring of the steroid nucleus of estrogen is aromatic. Estradiol has OH groups attached to carbons 3 and.17.
Androgens, This Steroid is produced in the adrenal cortex and the testes Having19 carbon atoms (Carbons 18 and 19 are in methyl groups) Testosterone is one of the more potent androgen Dehydroepiandrosterone (DHA), unlike testosterone, is a 17-ketosteroid
Animal Steroids
CH3 CH3 A B HO C D
CHOLESTEROL
OH CH3 CH3 CH3 OH CH3
FREE CHOLESTEROL
OH CH3 CH3 O
HO
TESTOSTERONE
ESTROGEN
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 Cortisol is a potent glucocorticoid with weak
raise the serum glucose level, and mineralocorticoids, which promote renal sodium retention
mineralocorticoid activity, whereas aldosterone is a potent mineralocorticoid (presumably due to its aldehyde group at carbon 18) but a weak glucocorticoid A hydroxyl or keto group at carbon 11 is found to correlate with glucocorticoid activity The urinary 17-hydroxycorticosteroid assay detects all 21-carbon steroids with a 17-OH group, such as cortisol
LIPOPROTEINS
Lipids must bind to proteins to make them watersoluble 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
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 protein Charged 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 Fredericksons type 1 hyperlipoproteinemia.
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 sphingosinebased phospholipids Membrane glycolipids include cerebrosides and Gangliosides
Biological Membrane
Non-polar Polar A PHOSPHOLIPID BILAYER
EXTRACELLULAR MEMBRANE PROTEIN
TRANS-MEMBRANE PROTEIN
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 MEMBRANES
Membrane Lipid
Phosphoglycerides
Sphingomyelin
Phosphoryl choline
Glycolipid
Cholesterol
OH group of C-3
Lipid Bilayer
Amphipathic
Hydrophilic: water-loving polar head group Hydrophobic: waterhating non-polar tails
The cell membrane is a mosaic of protein molecules bobbing in a fluid bilayer of phospholipids.
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
Cholesterol
Most common sterol in membranes Generally more abundant toward the outside of the plasma membrane Intercalates among phospholipids (Murray et al., 1996)
Perilla oil Flaxseed oil Manhattan Herring oil Canola oil Walnut oil
6 3 19 5 7
2 7 4 2 2
17 21 13 53 50
15 16 1 22 16
61 53 1 10 10
Soybean oil
Butter/milkfat Beef fat Palm oil Olive oil Corn oil Sunflower seed oil Borage seed oil Evening primrose oil Safflower seed oil
11
25 29 45 14 11 6 11 6 7
4
11 20 5 3 2 4 4 1 3
23
26 42 38 71 25 24 16 11 15
51
2 2 10 10 55 65 39 72 75
7
2 0 0 0 0 0 0 1 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 methyleneinterrupted 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
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
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, nonpolar 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)