LIPIDS

1
LIPIDS

• By
• Henry Wormser, Ph.D.

PSC 3110 Fall semester 2008
2
Introduction

• Definition water insoluble compounds
• Most lipids are fatty acids or ester of fatty
  acid
• They are soluble in non-polar solvents such as
  petroleum ether, benzene, chloroform
• Functions
• Energy storage
• Structure of cell membranes
• Thermal blanket and cushion
• Precursors of hormones (steroids and
  prostaglandins)
• Types
• Fatty acids
• Neutral lipids
• Phospholipids and other lipids

3
Fatty acids

• Carboxylic acid derivatives of long chain
  hydrocarbons
• Nomenclature (somewhat confusing)
• Stearate stearic acid C180 n-octadecanoic
  acid
• General structure

4
Fatty acids

• Common fatty acids
• n 4 butyric acid (butanoic acid)
• n 6 caproic acid (hexanoic acid)
• n 8 caprylic acid (octanoic acid)
• n 10 capric acid (decanoic acid)

5
Fatty acids

• common FAs
• n 12 lauric acid (n-dodecanoic acid C120)
• n 14 myristic acid (n-tetradecanoic acid
  C140)
• n 16 palmitic acid (n-hexadecanoic acid
  C160)
• n 18 stearic acid (n-octadecanoic acid C180)
• n 20 arachidic (eicosanoic acid C200)
• n 22 behenic acid
• n 24 lignoceric acid
• n 26 cerotic acid

6
Less common fatty acids

• iso isobutyric acid
• anteiso
• odd carbon fatty acid propionic acid
• hydroxy fatty acids ricinoleic acid,
  dihydroxystearic acid, cerebronic acid
• cyclic fatty acids hydnocarpic, chaulmoogric
  acid

7
PHYTANIC ACID
A plant derived fatty acid with 16 carbons and
branches at C 3, C7, C11 and C15. Present in
dairy products and ruminant fats. A peroxisome
responsible for the metabolism of phytanic acid
is defective in some individuals. This leads to a
disease called Refsums disease Refsums disease
is characterized by peripheral polyneuropathy,
cerebellar ataxia and retinitis pigmentosa
8
Less common fatty acids
These are alkyne fatty acids
9
Fatty acids

• Fatty acids can be classified either as
• saturated or unsaturated
• according to chain length
• short chain FA 2-4 carbon atoms
• medium chain FA 6 10 carbon atoms
• long chain FA 12 26 carbon atoms
• essential fatty acids vs those that can be
  biosynthesized in the body
• linoleic and linolenic are two examples of
  essential fatty acid

10
Unsaturated fatty acids

• Monoenoic acid (monounsaturated)

Double bond is always cis in natural fatty
acids. This lowers the melting point due to
kink in the chain
11
Unsaturated fatty acids

• Dienoic acid linoleic acid

12
Unsaturated fatty acids

• Various conventions are in use for indicating the
  number and position of the double bond(s)

13
Unsaturated fatty acids

• Polyenoic acid (polyunsaturated)

14
Unsaturated fatty acids

• Monoenoic acids (one double bond)
• 161, 9 w7 palmitoleic acid (cis-9-hexadecenoic
  acid
• 181, 9 w9 oleic acid (cis-9-octadecenoic acid)
• 181, 9 w9 elaidic acid (trans-9-octadecenoic
  acid)
• 221, 13 w9 erucic acid (cis-13-docosenoic acid)
• 241, 15 w9 nervonic acid (cis-15-tetracosenoic
  acid)

15
Unsaturated fatty acids

• Trienoic acids (3 double bonds)
• 1836,9,12 w6 g-linolenic acid (all
  cis-6,9,12-octadecatrienoic acid)
• 183 9,12,15 w3 a-linolenic acid
  (all-cis-9,12,15-octadecatrienoic acid)
• Tetraenoic acids (4 double bonds)
• 204 5,8,11,14 w6 arachidonic acid
  (all-cis-5,8,11,14-eicosatetraenoic acid)

16
Unsaturated fatty acids

• Pentaenoic acid (5 double bonds)
• 205 5,8,11,14,17 w3 timnodonic acid or EPA
  (all-cis-5,8,11,14,17-eicosapentaenoic acid)
• Hexaenoic acid (6 double bonds)
• 226 4,7,10,13,16,19 w3 cervonic acid or DHA
  (all-cis-4,7,10,13,16,19-docosahexaenoic acid)

Both FAs are found in cold water fish oils
17
Typical fish oil supplements
18
Properties of fats and oils

• fats are solids or semi solids
• oils are liquids
• melting points and boiling points are not usually
  sharp (most fats/oils are mixtures)
• when shaken with water, oils tend to emulsify
• pure fats and oils are colorless and odorless
  (color and odor is always a result of
  contaminants) i.e. butter (bacteria give
  flavor, carotene gives color)

19
Examples of oils

• Olive oil from Oleo europa (olive tree)
• Corn oil from Zea mays
• Peanut oil from Arachis hypogaea
• Cottonseed oil from Gossypium
• Sesame oil from Sesamum indicum
• Linseed oil from Linum usitatissimum
• Sunflower seed oil from Helianthus annuus
• Rapeseed oil from Brassica rapa
• Coconut oil from Cocos nucifera

20
Non-drying, semi-drying and drying oils

• based on the ease of autoxidation and
  polymerization of oils (important in paints and
  varnishes)
• the more unsaturation in the oil, the more likely
  the drying process
• Non-drying oils
• Castor, olive, peanut, rapeseed oils
• Semi-drying oils
• Corn, sesame, cottonseed oils
• Drying oils
• Soybean, sunflower, hemp, linseed, tung, oiticica
  oils

21
Fatty acid reactions

• salt formation
• ester formation
• lipid peroxidation

22
Soaps

• Process of formation is known as saponification
• Types of soaps
• Sodium soap ordinary hard soap
• Potassium soap soft soap (shaving soaps are
  potassium soaps of coconut and palm oils)
• Castile soap sodium soap of olive oil
• Green soap mixture of sodium and potassium
  linseed oil
• Transparent soap contains sucrose
• Floating soap contains air
• Calcium and magnesium soaps are very poorly water
  soluble (hard water contains calcium and
  magnesium salts these insolubilize soaps)

23
Lipid peroxidation

• a non-enzymatic reaction catalyzed by oxygen
• may occur in tissues or in foods (spoilage)
• the hydroperoxide formed is very reactive and
  leads to the formation of free radicals which
  oxidize protein and/or DNA (causes aging and
  cancer)
• principle is also used in drying oils (linseed,
  tung, walnut) to form hard films

24
Hydrogenated fats

• hydrogenation leads to either saturated fats and
  or trans fatty acids
• the purpose of hydrogenation is to make the
  oil/fat more stable to oxygen and temperature
  variation (increase shelf life)
• example of hydrogenated fats Crisco, margarine

25
(No Transcript)
26
Neutral lipids

• Glycerides (fats and oils) glycerides
• Glycerol
• Ester of glycerol - mono glycerides,
  diglycerides and triglycerides
• Waxes simple esters of long chain alcohols

27
GLYCERIDES
Function storage of energy in compact form and
cushioning
28
Stereospecific numbering

• carbon 2 of triglycerides is frequently
  asymmetric since C-1 and C-3 may be substituted
  with different acyl groups
• by convention we normally draw the hydroxyl group
  at C-2 to the left and use the designation of sn2
  for that particular substituent
• C-1 and C-3 of the glycerol molecule become sn1
  and sn3 respectively

29
Analytical methods to evaluate lipids

• saponification number
• iodine value (Hanus method)
• free fatty acids
• acetyl number
• Reichert-Meissl number
• HPLC/GC (for more precise analysis)

30
Saponification number

• gives some clue as to the average size of fatty
  acids in a given sample of fat
• defined as the number of milligrams of KOH needed
  to neutralize the fatty acids in 1 Gm of fat
• butter (large proportion of short chain FAs) sap.
  no. 220 230
• oleomargarine (long chain FAs) sap. No is 195 or
  less

31
Iodine number

• measures the degree of unsaturation in a given
  amount of fat or oil
• the iodine number is the number of grams of
  iodine absorbed by 100 grams of fat
• Cottonseed oil 103 111
• Olive oil 79 88
• Linseed oil 175 202
• frequently used to determine adulteration of
  commercial lots of oils

32
Acetyl number

• some fatty acids have hydroxyl groups

The acetyl number gives the proportion of these
hydroxyl-containing fatty acids in a given sample
of fat or oil
33
Acetyl number

• the acetyl number is the number of milligrams of
  KOH needed to neutralize the acetic acid of 1 Gm
  of acetylated fat
• examples
• castor oil 146 150
• cod liver oil 1.1
• cottonseed oil 21 25
• olive oil 10.5
• peanut oil 3.5

34
Reichert Meissl number

• measures the amount of volatile fatty acids (low
  MW and water soluble Fas)
• the R-M number is the number of milliliters of
  0.1N alkali required to neutralize the soluble
  fatty acids distilled from 5 Gm of fat
• butter fat has a high R-M number

35
WAXES

• simple esters of fatty acids (usually saturated
  with long chain monohydric alcohols)

Beeswax also includes some free alcohol and
fatty acids Spermaceti contains cetyl palmitate
(from whale oil) useful for Pharmaceuticals
(creams/ointments tableting and
granulation) Carnauba wax from a palm tree from
brazil a hard wax used on cars and boats
36
Spermaceti source
Carnauba wax source
Bees wax
37
Waxes
Examples of long chain monohydric alcohols found
in waxes
38
Phospholipids

• the major components of cell membranes
• phosphoglycerides

Phospholipids are generally composed of FAs, a
nitrogenous base, phosphoric acid and either
glycerol, inositol or sphingosine
39
(No Transcript)
40
Phosphatidyl inositol
Commonly utilized in cellular signaling
41
Sphingolipids
Based on sphingosine instead of glycerol
42
Sphingomyelin (a ceramide)
It is a ubiquitous component of animal cell
membranes, where it is by far the most abundant
sphingolipid. It can comprise as much as 50 of
the lipids in certain tissues, though it is
usually lower in concentration than
phosphatidylcholine
43
Ether glycerophospholipids

• Possess an ether linkage instead of an acyl group
  at the C-1 position of glycerol
• PAF ( platelet activating factor)
• A potent mediator in inflammation, allergic
  response and in shock (also responsible for
  asthma-like symptom
• The ether linkage is stable in either acid or
  base
• Plasmalogens cis a,b-unsaturated ethers
• The alpha/beta unsaturated ether can be
  hydrolyzed more easily

44
Ether glycerophospholipids
45
glycolipids
There are different types of glycolipids
cerebrosides, gangliosides, lactosylceramides
46
GLYCOLIPIDS

• Cerebrosides
• One sugar molecule
• Galactocerebroside in neuronal membranes
• Glucocerebrosides elsewhere in the body
• Sulfatides or sulfogalactocerebrosides
• A sulfuric acid ester of galactocerebroside
• Globosides ceramide oligosaccharides
• Lactosylceramide
• 2 sugars ( eg. lactose)
• Gangliosides
• Have a more complex oligosaccharide attached
• Biological functions cell-cell recognition
  receptors for hormones

47
Gangliosides

• complex glycosphingolipids that consist of a
  ceramide backbone with 3 or more sugars
  esterified,one of these being a sialic acid such
  as N-acetylneuraminic acid
• common gangliosides GM1, GM2, GM3, GD1a, GD1b,
  GT1a, GT1b, Gq1b

48
Ganglioside nomenclature

• 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

49
Ganglioside nomenclature

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

50
A ganglioside (GM1)
51
Cardiolipids
A polyglycerol phospholipid makes up 15 of
total lipid-phosphorus content of the myocardium
associated with the cell membrane
Cardiolipids are antigenic and as such are used
in serologic test for syphilis (Wasserman test)
52
Sulfolipids

• also called sulfatides or cerebroside sulfates
• contained in brain lipids
• sulfate esters of cerebrosides
• present in low levels in liver, lung, kidney,
  spleen, skeletal muscle and heart
• function is not established

53
Lipid storage diseases

• also known as sphingolipidoses
• genetically acquired
• due to the deficiency or absence of a catabolic
  enzyme
• examples
• Tay Sachs disease
• Gauchers disease
• Niemann-Pick disease
• Fabrys disease
• http//www.ninds.nih.gov/disorders/lipid_storage_d
  iseases/lipid_storage_diseases.htm

54
Genetic defects in ganglioside metabolism

• leads to a buildup of gangliosides (ganglioside
  GM2) in nerve cells, killing them

55
Tay-Sachs disease

• a fatal disease which is due to the deficiency of
  hexosaminidase A activity
• accumulation of ganglioside GM2 in the brain of
  infants
• mental retardation, blindness, inability to
  swallow
• a cherry red spot develops on the macula (back
  of the the eyes)
• Tay-Sachs children usually die by age 5 and often
  sooner

56
Genetic defects in globoside metabolism

• Fabrys disease
• Accumulation of ceramide trihexoside in kidneys
  of patients who are deficient in lysosomal
  a-galactosidase A sometimes referred to as
  ceramide trihexosidase
• Skin rash, kidney failure, pains in the lower
  extremities
• Now treated with enzyme replacement therapy
  agalsidase beta (Fabrazyme)

57
Genetic defects in cerebroside metabolism

• Krabbes disease
• Also known as globoid leukodystrophy
• Increased amount of galactocerebroside in the
  white matter of the brain
• Caused by a deficiency in the lysosomal enzyme
  galactocerebrosidase
• Gauchers disease
• Caused by a deficiency of lysosomal
  glucocerebrosidase
• Increase content of glucocerebroside in the
  spleen and liver
• Erosion of long bones and pelvis
• Enzyme replacement therapy is available for the
  Type I disease (Imiglucerase or Cerezyme)
• Also miglustat (Zavesca) an oral drug which
  inhibits the enzyme glucosylceramide synthase, an
  essential enzyme for the synthesis of most
  glycosphingolipids

58
Miglustat (Zavesca)
59
Genetic defects in ganglioside metabolism

• Metachromatic leukodystrophy
• accumulation of sulfogalactocerebroside
  (sulfatide) in the central nervous system of
  patient having a deficiency of a specific
  sulfatase
• mental retardation, nerves stain yellowish-brown
  with cresyl violet dye (metachromasia)
• Generalized gangliosidosis
• accumulation of ganglioside GM1
• deficiency of GM1 ganglioside b-galactosidase
• mental retardation, liver enlargement, skeletal
  involvement

60
Niemann-Pick disease

• principal storage substance sphingomyelin which
  accumulates in reticuloendothelial cells
• enzyme deficiency sphingomyelinase
• liver and spleen enlargement, mental retardation

61
Blood groups

• determined by various glycolipids on RBCs
• A antigens
• B antigens
• H antigens

(found on type O blood cells)
not recognized by anti-A or anti-B antibodies
62
Cholesterol and cholesterol esters
63
STEROID NUMBERING SYSTEM
64
STEREOCHEMISTRY OF STEROIDS
65
Cholesterol sources, biosynthesis and degradation

• diet only found in animal fat
• biosynthesis primarily synthesized in the liver
  from acetyl-coA biosynthesis is inhibited by LDL
  uptake
• degradation only occurs in the liver

66
Cholesterol and cholesterol esters
The hydroxyl at C-3 is hydrophilic the rest of
the molecule is hydrophobic also 8 centers of
asymmetry
67
Cholesterol and cholesterol esters
Functions -serves as a component of membranes of
cells (increases or moderates
membrane fluidity -precursor
to steroid hormones -storage
and transport cholesterol esters

68
Functions of cholesterol

• serves as a component of membranes of cells
  (increases or moderates membrane fluidity)
• precursor to steroid hormones and bile acids
• storage and transport cholesterol esters

69
Prostaglandins and other eicosanoids (prostanoids)

• local hormones, unstable, key mediators of
  inflammation
• derivatives of prostanoic acid

70
(No Transcript)
71
(No Transcript)
72
SUBSTITUTION PATTERN OF PROSTANOIDS
73
Prostacyclins, thromboxanes and leukotrienes

• PGH2 in platelets is converted to thromboxane A2
  (TXA2) a vasoconstrictor which also promotes
  platelet aggregation
• PGH2 in vascular endothelial cells is converted
  to PGI2, a vasodilator which inhibits platelet
  aggregation
• Aspirins irreversible inhibition of platelet COX
  leads to its anticoagulant effect

74
Functions of eicosanoids

• Prostaglandins particularly PGE1 block
  gastric production and thus are gastric
  protection agents
• Misoprostol (Cytotec) is a stable PGE1 analog
  that is used to prevent ulceration by long term
  NSAID treatment
• PGE1 also has vasodilator effects
• Alprostadil (PGE1) used to treat infants with
  congenital heart defects
• Also used in impotance (Muse)

75
Functions of eicosanoids

• PGF2a causes constriction of the uterus
• Carboprost Hebamate (15-Me-PGF2a) induces
  abortions
• PGE2 is applied locally to help induce labor at
  term

76
Examples of drugs derived from prostaglandins
77
(No Transcript)
78
Leukotrienes
Leukotrienes are derived from arachidonic acid
via the enzyme 5-lipoxygenase which converts
arachidonic acid to 5-HPETE (5-hydroperoxyeicosat
etranoic acid) and subsequently by dehydration to
LTA4
peptidoleukotrienes
79
Leukotrienes
Leukotrienes are synthesized in neutrophils,
monocytes, macrophages, mast cells and
keratinocytes. Also in lung, spleen, brain and
heart. A mixture of LTC4, LTD4 and LTE4 was
previously known as the slow-reacting substance
of anaphylaxis
peptidoleukotrienes
80
Leukotrienes
Non-peptidoleuktrienes LTA4 is formed by
dehydration of 5-HPETE, and LTB4 by hydrolysis of
the epoxide of LTA4
81
Biological activities of leukotrienes

• 1. LTB4 - potent chemoattractent
• - mediator of hyperalgesia
• - growth factor for keratinocytes
• 2. LTC4 - constricts lung smooth muscle
• - promotes capillary leakage
• 1000 X histamine
• 3. LTD4 - constricts smooth muscle lung
• - airway hyperactivity
• - vasoconstriction
• 4. LTE4 - 1000 x less potent than LTD4
• (except in asthmatics)

82
Leukotriene receptor antagonists
Zafirlukast (Accolate)
Montelukast (Singulair)
83
Lipid-linked proteins

• Lipid-linked proteins (different from
  lipoproteins)
• lipoproteins that have lipids covalently attached
  to them
• these proteins are peripheral membrane proteins

84
Lipid-linked proteins

• 3 types are most common
• Prenylated proteins
• Farnesylated proteins (C15 isoprene unit)
• Geranylgeranylated proteins (C20 isoprene unit)
• Fatty acylated proteins
• Myristoylated proteins (C14)
• Palmitoylated proteins (C16)

85
Lipid-linked proteins

• glycosylphosphatidylinositol-linked proteins
  (GPI-linked proteins)
• occur in all eukaryotes, but are particularly
  abundant in parasitic protozoa
• located only on the exterior surface of the
  plasma membrane

86
Fatty acylated proteins
87
Prenylated proteins
88
GPI-linked proteins
89
Lipoproteins

• particles found in plasma that transport lipids
  including cholesterol
• lipoprotein classes
• chylomicrons take lipids from small intestine
  through lymph cells
• very low density lipoproteins (VLDL)
• intermediate density lipoproteins (IDL)
• low density lipoproteins (LDL)
• high density lipoproteins (HDL)
• Terpenes

90
Composition and properties of human lipoproteins
most proteins have densities of about 1.3 1.4
g/mL and lipid aggregates usually have densities
of about 0.8 g/mL
91
Lipoprotein structure
92
LDL molecule
93
The apolipoproteins

• major components of lipoproteins
• often referred to as aproteins
• classified by alphabetical designation (A thru E)
• the use of roman numeral suffix describes the
  order in which the apolipoprotein emerge froma
  chromatographic column
• responsible for recognition of particle by
  receptors

94
HELICAL WHEEL PROJECTION OF A PORTION OF
APOLIPOPROTEIN A-I
95
LIPOPROTEINS

• spherical particles with a hydrophobic core (TG
  and esterified cholesterol)
• apolipoproteins on the surface
• large apoB (b-48 and B-100) atherogenic
• smaller apoA-I, apoC-II, apoE
• classified on the basis of density and
  electrophoretic mobility (VLDL LDL IDLHDL
  Lp(a)

96
Apoproteins of human lipoproteins

• A-1 (28,300)- principal protein in HDL
• 90 120 mg in plasma
• A-2 (8,700) occurs as dimer mainly in HDL
• 30 50 mg
• B-48 (240,000) found only in chylomicron
• B-100 (500,000) principal protein in LDL
• 80 100 mg

97
Apoproteins of human lipoproteins

• C-1 (7,000) found in chylomicron, VLDL, HDL
• 4 7 mg
• C-2 (8,800) - found in chylomicron, VLDL, HDL
• 3 8 mg
• C-3 (8,800) - found in chylomicron, VLDL, IDL,
  HDL
• 8 15 mg
• D (32,500) - found in HDL
• 8 10 mg
• E (34,100) - found in chylomicron, VLDL, IDL HDL
• 3 6 mg

98
Major lipoprotein classes

• chylomicrons
• density
• diameter 80 - 500 nm
• dietary triglycerides
• apoB-48, apoA-I, apoA-II, apoA-IV, apoC-II/C-III,
  apoE
• remains at origin in electrophoretic field

99
Major lipoprotein classes

• VLDL
• density 1.006
• diameter 30 - 80nm
• endogenous triglycerides
• apoB-100, apoE, apoC-II/C-III
• prebeta in electrophoresis

100
Major lipoprotein classes

• IDL (intermediate density lipoproteins)
• density 1.006 - 1.019
• diameter 25 - 35nm
• cholesteryl esters and triglycerides
• apoB-100, apoE, apoC-II/C-III
• slow pre-beta

101
Major lipoprotein classes

• HDL (high density lipoproteins)
• density 1.063-1.210
• diameter 5-12nm
• cholesteryl esters and phospholipids
• apoA-I, apoA-II, apoC-II/C-III
• alpha (electrophoresis)

102
Major lipoprotein classes

• LDL (low density lipoproteins)
• density 1.019 - 1.063
• diameter 18-25nm
• cholesteryl esters
• apoB-100
• beta (electrophoresis)
• borderline high and 160 is high

103
Cholesterol and lipid transport by lipoproteins
104
Cholesterol and lipid transport by lipoproteins
105
(No Transcript)
106
(No Transcript)
107
Photograph of an arterial plaque
108
The LDL receptor

• characterized by Michael Brown and Joseph
  Goldstein (Nobel prize winners in 1985)
• based on work on familial hypercholesterolemia
• receptor also called B/E receptor because of its
  ability to recognize particles containing both
  apos B and E
• activity occurs mainly in the liver
• receptor recognizes apo E more readily than apo
  B-100

109
Representation of the LDL receptor
110
Terpenes

• simple lipids, but lack fatty acid component
• formed by the combination of 2 or more molecules
  of 2-methyl-1,3-butadiene (isoprene)
• monoterpene (C-10) made up of 2 isoprene units
• sesquiterpene (C-15) made up of 3 isoprene
  units
• diterpene (C-20) made up of 4 isoprene units

111
Monoterpenes
Monoterpenes are readily recognized by their
characterisitic flavors and odors ( limonene in
lemons, citronellal in roses and
geraniums, pinene in turpentine and menthol from
peppermint
112
Sesquiterpenes
113
Diterpenes
All-trans-retinal
114
Triterpenes
Triterpenes are C-30 compounds are addition
products of 2 sesquiterpenes Both squalene and
lanosterol are precursors of cholesterol and
other steroids
115
Other terpenes

• tetraterpenes (C-40) are not as common as mono,
  di, and triterpenes
• include the carotenoids such as beta-carotene
  (precursor of vitamin A) and lycopene found in
  tomatoes
• usually colorful compounds due to highly
  conjugated system
• polyisoprenoids or polyprenols consist of
  numerous isoprene adducts (8 22)
• examples include dolichol phosphate, undecaprenyl
  alcohol (bactoprenol) and the side chains of
  vitamins K, vitamin E and coenzyme Q

116
Websites on lipids

• http//www.cyberlipid.org/ web site deals mainly
  with an overview on all lipids
• http//www.lipidsonline.org this website
  focuses mainly on disease processes
  (atherosclerosis) and treatment
• http//www.lipidlibrary.co.uk/ -There are two
  main divisions in this website, one dealing with
  the chemistry and biochemistry of lipids and the
  other with the analysis of lipids

117
The End