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LIPIDS AND INTRODUCTORY LIPIDOMICS
OUTLINE:
➢ Introduction, definition and brief function of lipids
➢ Classification of lipids
➢ Storage lipids
➢ Fatty acids
➢ Triglycerides
➢ Waxes
➢ Structural lipids
➢ Glycerophospholipids
➢ Galactolipids and sulpholipids
➢ Acheal ether lipids
➢ Sphingolipids
➢ Sterols
➢ Functional metabolite & biosignalling activities of lipids:
➢ Chemistry and methods of lipid analysis

Lipids are diverse groups of compounds, whose common defining feature is their
insolubility in water
...
Fat and oil are principal stored form of energy in organisms
2
...

3
...

Various classifications of lipids are in use, including:
1
...
Simplelipids: neutral fats and waxes
b
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derived lipids: fatty acids, steroids, vitamins, carotenoids, etc
...

a
...

b
...

c
...


For the purpose of simplicity, we will classify and study lipids under two broad headings
(using functional classification) in this lecture:
1
...
Membrane lipids

STORAGE LIPIDS
FATTY ACIDS, ACYL GLYCEROLS AND WAXES
Fats and oils are derivatives of fatty acids and are stored form of energy for organisms, as
the oxidation of fatty acids is highly exergonic
...
The
fatty acid chain may be branched or unbranched, saturated or unsaturated
...

Usually, most occurring fatty acids have even number of carbon atoms, in an unbranched
chain of 12-24 carbons(a result of acetate inclusion during biosynthesis)

Also, more often; when fatty acids appear to be unsaturated, the double bond is usually in
Cis form between C9 and C10 designated Δ9, and other double (if present) bonds are
usually in the form and sequence Δ12, Δ15 (arachidonic acid is an exception)
...


In addition, physical properties of fatty acids is a function of chain length and degree of
saturation, the longer the fatty acyl chain and fewer the double bond, the lower the
solubility in water, for example saturated fatty acid of 12:0 to 24:0 are solid at room
temperature, while unsaturated fatty acids of same length are liquid at room temperature
...
In contrast, double bond induces a constriction and
steric hindrance, thus folding is never tight
FATS
Triacylglycerols, otherwise known as fats or triglyceridesare cmposed of three fatty acids;
each in ester linkage with the –OH groups of a single glycerol
...

Fats are often founds as oily cytosolic droplets of eukaryotic cells, invertebrates; there are
specialized cells (adipocytes) that stores large amount of triacylglycerides
...

Often times, eukaryotic cells specialized for storing fats( e
...

Why are triacylglycerols somewhat preferably efficient fuel store than polysaccharides ?
1
...
Triacylglycerols are hydrophobic and therefore unhydrated, therefore they carry no
extra weight of water of hydration when transported as fuel
...
The body can accumulate triglycerides much enough for one month energy supply,
whereas the body can store less than a day body energy supply in form of glycogen
Triglycerides stored under skin also function as insulators against harsh temperature, they
confer buoyancy in some other organisms
...
This oxidation produces
aldehydes and carboxylic acids of shorter chain length which are often volatile with
unpleasant odour and taste
...
However, this practise also has a defect of converting
some of the Cis double bonds to Trans configuration which has been indicted to be
associated with cardiovascular health risks, inflammation and autoimmunity
WAXES
Biological waxes are esters of long chain(C14-C36) saturated fatty acid with long chain
alcohols(C16-C30)
...
Waxes functions
biologically as metabolic fuel store, water repellant
...
In plants, waxes gives some leaves their shiny and thick
appearance which prevents evaporation and parasite attack
Biological waxes has also found large variety of use industrially as pharmaceuticals,
cosmetics etc

MEMBRANE (STRUCTURAL) LIPIDS
Biological membranes are known for their structural double layer of lipids, which is
selectively permeable
...

Generally, there are 5 types of membrane lipids viz
1
...


Galactolipids and Sulpholipids

3 Archeal tetraether lipids

4
...
Sterols (Isoprene derivatives)
The hydrophilic moiety in a membrane lipid may be a single or more –OH group, and
could be a phosphodiester linkage as in phospholipids, it could also be a simple sugar
(glycolipids)
...

Phosphoglycrides are often named as derivaives of their parent compound “Phosphatidic
acid”, groups bonded to the glycerol via the phosphodiester bond could include serine,
ethanolamine, choline, inositol, and named as follows phosphatidyl serine, etc
...

Phosphatidylcholine also called as lecith It is the major phospholipid of cell membrane
...

Phosphatidyl ethanolamine and phosphatidyl serine are called as cephalins and
aminophospholipids
...

Phosphatidyl inositol is also a component of cell membrane
...

Also, it is worthy of note that some biologically important glycerophosholipids have ether
linked fatty acids, in which one of their two acyl groups is attached to glycerol in ether as
against the normal ester
...
The head groups being
ethanolamine and choline in plasmalogen and platelet activating factor respectively
...
Thylakoid membrane of plant
chloroplast are rich in galactolipids
...
These linkages are through ether bonds, which are
much more stable to hydrolysis at low pH and high temperature than are the ester bonds
...
The general name for this category is glycerol-dialkylglycerol-tetraethers (GDGTs)

SPHINGOLIPIDS
Sphingolipids are stucturally constituted by a molecule of a long chain amino alcohol
“Sphingosine” or one of its derivatives, a molecule of long chain fatty acid and a polar head
group
...

Fatty acid is often attached to the sphingosine C2 in an amide linkage to the –NH2 of the
sphingosine to form the “Ceramide” the parent molecule of all sphingolipids
...
Sphingomyelin
2
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Gangliosides
1
...
They are found in the animal
plasma membranes, especially in the myelin which surrounds and insulate the axon
2
...
When the polar head
group is a monosaccharide e
...
Gangliosides: these sphingolopids are structurally similar to globosides, but more
complex in that in addition to its oligosaccharide polar group, it also has one or
more residues of N-acetylneuraminic acid(sialic acid) on the oligosaccharides
...
Soon
the functions are discovered and described as:
1
...
Some serve as important recognition site on cellular surfaces
3
...
Some help in neuronal coordination, conduction and insulation of electrical charges
and impulses
...
Sterols are
structurally characterized by its steroid nucleus of four fused carbon rings; three with six
carbon and the fourth with five carbon
...
In eukaryotes, sterols(as well as fat soluble
vitamins, quinones and dolichols) are synthesized from condensation of isoprene subunits
Cholesterol, the most common sterol in animal tissue is amphiphatic with a polar –OH
group at C3 and a non-polar hydrocarbon body attached to the steroid nucleus at C17
Aside its role as a membrane constituent , sterols are precursors for a variety of
biologically active products, they also serve as biological signals of regulation e
...

Bile acids acid as well is a polar derivative of cholesterol, and functions as an emulsifying
agent
...
Its is convincing to take a
quick peep into degradation of some and highlight related clinical relevance's and
associated inborn errors
...
Another enzyme
“Lysophospholipase” cleaves off the the remaining fatty acyl ester linkage
...
Disorders of ganglioside breakdown are
responsible for several hereditary sphingolipid storage diseases, such as Tay-Sachs disease,
which are characterized by an invariably fatal neurological deterioration in early
childhood
...

Few activities of lipids in this category will be discussed
...
Phosphatidylinositol and its phosphorylated derivatives are cellular metabolism
regulators and structural chaperones:
Phosphatidylinositol 4,5-bisphosphate in the cytoplasmic inner face of plasma
membranes serves as a specific binding site for certain cytoskeletal proteins and for
some soluble proteins involved in membrane fusion during exocytosis
...

The signals act through a series of steps that begins with enzymatic removal of a
phospholipid head group and ends with activation of an enzyme (protein kinase C),
as seen for example in the biomechanism of the hormone vasopressin
...


IP3 triggers release of Ca2+ from the endoplasmic reticulum, and the combination
of diacylglycerol and elevated cytosolic Ca2+ activates the enzyme protein kinase C
...


2
...
g
both ceramide and sphingomyelin are potent regulators of protein kinases;
regulators of cell division differentiation, migration and apoptosis
3
...
In vertebrates, eicosanoids are
of three classes:

a
...
It regulates
and
stimulate smooth muscle contraction, blood
flow
to
certain
organs,
inflammation and pain, sleep-wake
cycle, body temperature
...
Thromboxane: a carbon ringed eicosanoid which has an
intrinsic
ether
link
...

c
...
It function as biosignals, usually fostering

contraction of smooth muscles
e
...

4
...
Steroid hormones are transported through
the blood to target tissues where they enter the cells and bind specific protein
receptors and trigger changes
...

Major steroid hormones include the sex hormones, corticosteroids, aldrosterone
...

Synthetic steroids are also used as drugs; most importantly anti-inflammatory
drugs
...
Fat soluble vitamins: these are vitamin A,D,E & k
...

Biologically active vitamin D known as Calcitriol functions as a hormone regulating
intestinal calcium uptake, blood calciun level and renal reabsorption of calcium,
calcitriol also regulates genetic expression of the calbidin transporter
...
Retinal is another vit
...

Vitamin E otherwise called “Tocopherols” contains substituted aromatic ring and a
long isoprenoid side chain
...
Tocopherols are biological
antioxidants, preventing ROS oxidative damages
Vitamin K undergoes a cycle of oxidation-reduction during the formation of
prothrombin in blood clot formation
Note that, often vit
...
K are known to belong to a group of “Redox lipids”
...

Ubiquinone (also called coenzyme Q) and plastoquinone are isoprenoids that function as
lipophilic electron carriers in the electron transport chain in mitochondria and
chloroplasts, respectively
...

Warfarin is a synthetic compound that inhibits the formation of active prothrombin
...


complex

Natural pigments: these include lipidic conjugated dienes, with the ability to exhibit
electronic excitation under visible light, yielding brilliant colouration
...

They are good pharmaceutical active compounds, example include erythromycin,
lovastatin
Also, vascular plants often produce varieties of volatile lipid compounds used as biosignals,
attractant, repellants
...


CHEMISTRY AND METHODS OF LIPID ANALYSIS
Lipids are hydrophobic and water insoluble, thus their extraction and subsequent
fractionation requires the application of techniques beyond those used in water soluble
molecules as carbohydrate and protein
...
g benzene, ethyl ether, chloroform
...
8, an homogenous mixture that help in lipid
extraction from homogenized tissues, after this lipid extraction, more water is added to the
resulting extract and the mixture separates into two phases, methanol/water (top phase)
and chloroform (bottom phase)
...

Complex mixtures of tissue lipids can be fractionated by chromatographic procedures
based on the different polarities of each class of lipid
...
The polar lipids bind
tightly to the polar silicic acid, but the neutral lipids are directly eluted through the column
and emerge in the first chloroform wash
...

Uncharged but polar lipids (cerebrosides, for example) are eluted with acetone, and very
polar or charged lipids (such as glycerophospholipids) are eluted with methanol
...
A thin
layer of silica gel is spread onto a glass plate, to which it adheres
...
As the solvent rises
on the plate by capillary action, it carries lipids with it
...
The separated lipids can be detected by
spraying the plate with a dye (rhodamine) that fluoresces when associated with lipids or by
exposing the plate to iodine fumes
...
A number of other spray reagents are also useful in detecting
specific lipids

Gas-liquid chromatography separates volatile components of a mixture according to their
relative tendencies to dissolve in the inert material packed in the chromatography column
and to volatilize and move through the column, carried by a current of an inert gas such as
helium
...

For an analysis of the fatty acids in a sample of phospholipids, the lipids are first heated in
a methanol/HCl or methanol/NaOH mixture, which converts fatty acids esterified to
glycerol into their methyl esters (in a process of transesterification
...
Those fatty acyl esters most soluble in the column
material partition into (dissolve in) that material; the less soluble lipids are carried by the
stream of inert gas and emerge first from the column
...
Using these techniques, mixtures of
fatty acids of various chain lengths and various degrees of unsaturation can be completely
resolved
...
For
example, all ester-linked fatty acids in triacylglycerols, phospholipids, and sterol esters are
released by mild acid or alkaline treatment, and somewhat harsher hydrolysis conditions
release amide-bound fatty acids from sphingolipids
...
g phospholipases, glycosilases ) are
also useful in the determination of lipid structure
...

To establish unambiguously the length of a hydrocarbon chain or the position of double
bonds, mass spectral analysis of lipids or their volatile derivatives is invaluable
...
When the effluent from a
chromatography column is sampled by mass spectrometry, however, the components of a
lipid mixture can be simultaneously separated and identified by their unique pattern of
fragmentation
...
Lipidomics also pose to
propose a new nomenclature system with which it is easier to compile and search and
compare lipids in a database
...
Analytically, mass
spectrometry earlier discussed has played a crucial role in the lipidomic database
compilation as it provide a wider resolution of lipids structure and composition
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All pieced together in a simplified easily digestible form for all and
sundry
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Lehningher principles of biochemistry, 6th edition, David Nelson & Micheal Cox
2
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Mallikarjuna Rao
3
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Murray, Granner, Mayer, Rodwell
4
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MN Chatterjea, Rana shinde
5
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David Metzler
6
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Donald & Judith Voet,
Charlotte Pratt

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...
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