3. Lipids (Greek: lipos, fat) are substances of biological
origin that are soluble in organic solvents such as
chloroform and methanol but are insoluble in water.
They are easily separated from other biological
materials by extraction into organic solvents and may
be further fractionated by such techniques as
adsorption chromatography, thin layer chromatography,
and reverse-phase chromatography.
Unlike proteins, nucleic acids, polysaccharides, lipids
are not polymers rather they are small molecules.
They are the chief storage form of energy, besides their
role in cellular structure and other biochemical
functions.
4. Fat is stored in adipose tissue, where it also serves as a
thermal insulator in the subcutaneous tissues.
Fatty acid derivatives serve as vitamins(A,D,E&K) or
hormones.
It act as energy/food reservoir (Triacylglycerol).
Several proteins are covalently modified by fatty acids.
Structural components of biological membranes
(lipoprotein, phospholipids & sphingomyelins) .
Lipids act as important cellular metabolic
regulators(steroid hormones).
Lipids are compounds in inner mitochondrial
membrane and participate in Electron transport chain.
6. Membranes are two layers thick sheath like
structures Formed by non-covalent assemblage of
lipids and proteins Carbohydrates.
Act as barriers to the passage of polar molecules
and ions.
Membrane lipids are amphipathic in nature that is
each has a hydrophilic part (polar, the phosphate
group plus whatever alcohol is attached to it, for
example, serine) & hydrophobic part (non-polar,
containing fatty acids or fatty acid–derived
hydrocarbons) parts.
The polar part of membrane lipid is represented as
‘Head’ and the non-polar part as ‘Tail’.
7.
8. Phospholipids are abundant in all biological
membranes.
A phospholipid molecule is constructed from four
components: one or more fatty acids, a platform to
which the fatty acids are attached, a phosphate, and
an alcohol attached to the phosphate.
Glycerol-3-phosphate is the backbone of all
phospholipids.
The fatty acid components provide a hydrophobic
barrier, whereas the remainder of the molecule has
hydrophilic properties that enable interaction with the
aqueous environment.
9. 1.Glycero-
phospholipids
:
Also called as
phosphoglycerides.
Major lipid
component of
biological
membrane.
Consists of glycerol-
3-phosphate, whose
C1 & C2 esterified by
fatty acids.
10. 2. Sphingo-phospholipids:
Sphingolipids, which are also major membrane
components, are derivatives of the C18 amino alcohols
Sphingosine.
All sphingolipids have, in addition to the sugar, a fatty
acid attached to the amino group of sphingosine.
N-acyl fatty acid derivative of sphingosine are known as
ceramide (A ceramide containing a fatty acid 30 carbons
long is (a major component of skin, and regulates skin’s
water permeability) occur only in small amounts in plant
and animal tissues but form the parent compounds of
more abundant sphingolipids:
Eg. Sphingomyelins, the most common sphingolipids,
are ceramides bearing either a phosphocholine or a
phosphoethanolamine moiety.
Among the sphingolipids, only sphingomyelin, a
phospholipid, is a major component of biological
membranes.
The membranous myelin sheath that surrounds and
electrically insulates many nerve cell axons is
11.
12. Lipids conjugated with carbohydrates.
Like the phospholipid sphingomyelin, glycolipids
are derivatives of ceramides in which a long-
chain fatty acid is attached to the amino alcohol
sphingosine. They are, therefore, called
glycosphingolipids.
glycosphingolipids are essential components of
all membranes in the body, but they are found in
greatest amounts in nerve tissue. They are
located in the outer leaflet of the plasma
membrane, where they interact with the
extracellular environment.
they play a role in the regulation of cellular
interactions, growth, and development.
13. • Glycosphingolipids are antigenic, and they have been
identified as a source of blood group antigens, various
embryonic antigens specific for particular stages of
fetal development, and some tumor antigens.
14. Neutral glycosphingolipids
1. Cerebrosides- simplest glycosphingolipids; ceramide
monosaccharides containing glucose or galactose units;
found predominantly in the brain and peripheral nervous
tissue
2. Globosides- They are produced by attaching additional
monosaccharides (including GalNAc) to a
glucocerebroside.
Acidic glycosphingolipids
These are negatively charged at physiologic pH. This
negative charge is provided by N-acetylneuraminic acid
(NANA, a sialic acid) in gangliosides, or by sulfate groups
in sulfatides.
1. Gangliosides- These are the most complex
glycosphingolipids; found primarily in the ganglion cells of
the central nervous system.
2. Sulfatides- These cerebrosides contain sulfated galactosyl
residues, and are therefore negatively charged at
physiologic pH. Sulfatides are found predominantly in
17. The two components are joined together by
glycerol molecule. The phosphate group
can be modified with simple organic
molecule such as “Choline”
18. There are four types of
phospholipids
1. Phosphotidylcholine :- It is the major
components of cell mambrane and is critical for
brain and liver function
2. Phosphotidylethanolamine :- It is the
most abundant phospholipids in animal and
plant lipids and is the key building block of cell
mambrane bilayer.
3. Phosphotidylinositol:- This is present in
all tissues and cell type. In cell membarne,it is
usually located on the inner side. It is abundant
23. OVERVIEW:
• Polar, ionic compounds.
• Composed of an alcohol that is
attached by a phosphodiester
bridge to either diacylglycerol or
sphingosine.
*****Glycerophospholipids and
sphingomyelin, a
sphingolipid containing phosphate,
are classified as phospholipids.*****
24. • Performed by enzymes: phospholipases found in
all tissues and pancreatic juice.
• enzyme hydrolyze the phosphodiester bonds
cleaving the phospholipids at specific site.
• Major enzymes responsible for degrading
phosphoglyserides are:
1. Phospholipase A1: They hydrolyze the ester
bonds of intact glycerophospholipids at C-1 of
glycerol. Found in mammalian tissues.
2. Phospholipase A2 : They hydrolyze the ester
bonds of intact glycerophospholipids at C-2 of
glycerol. Found in mammalian tissues, pancreatic
juices, snake, bee venoms.
25. Inhibited by glucocorticoids( e.g. : cortisol).
3. Phospholipase C : Splits one of the
phosphodiester bonds in head group. Found in
liver lysosome and alpha toxin of Clostridia and
other Bacilli.
4. Phospholipase D : Splits one of the
phosphodiester bonds in head group. Found
primarily in plant tissues.
26. • Phospholipase release molecules that can serve
as messengers( diacylglycerol and inositol 1,4,5-
triphosphate) or that are substrates for synthesis of
messengers( e.g. arachidonic acid)
• Phospholipases are responsible not only for
degrading phospholipids, but also for “remodeling”
them. For example, phospholipases A1 and A2
remove specific fatty acids from membrane- bound
phospholipids; these can be replaced with
alternative fatty acids using fatty acyl CoA
transferase.
27. • It is a type of sphingolipid found in animal cell
membranes.
• It consists of phosphocholine and ceramide or a
phosphoethanolamine head group.
• Degraded by sphingomyelinase, a lysosomal enzyme
that hydrolytically removes phosphorylcholine, leaving a
ceramide.
• The ceramide, is in turn cleaved by ceramidase into
sphingosine and a free fatty acid.
NIEMANN-PICK DISEASE( type A and type B)
• Autosomal recessive disorder.
• Caused by inability to degrade sphingomyelin due
to deficiency of enzyme sphingomyelinase.
• In severe infantile form ( type A) , liver and spleen are
primary sites for lipid deposits and therefore they
become enlarged. Such infants suffers from
neurodegeneration and die in childhood.
28. A less severe variant (type B) causes little to no
damage to neural tissue, but lungs , spleen, liver
and bone marrow are affected.
30. • Glycolipids are molecules that
contain both carbohydrate and lipid
components.
• In contrast to sphingomyelin they
do not have a phosphocholine
group.
• They are derivatives of ceramides
in which a long chain fatty acid is
attached to the amino alcohol
sphingosine. Therefore they are
more precisely called as
glycosphingolipids.
• Glycolipids are essential
components of cell plasma
membranes (outer leaflet), but are
most abundant in nervous tissues.
31. • Glycolipids are often found as
markers on cell membranes and
play a large role in tissue and organ
specificity.
• They are the markers for
recognizing ABO blood group
system.
32.
33. The enzymes responsible for catalyzing the stepwise
addition of monosaccharides to ceramide and ceramide-
bound oligosaccharides are the glycolipid
glycosyltransferases, or GGTs.
These enzymes recognize both glycosphingolipids and
glycoproteins as substrates.
34. Biosynthesis of GSLs initiates at cytoplasmic face of
the endoplasmic reticulum (ER) by serine and
palmitoyl-CoA condensation that ultimately
generates ceramide.
35. Glycosphingolipid synthesis occurs primarily in the
golgi by sequential addition of glycosyl monomers
transferred from UDP-sugar donors to the acceptor
molecules.
Glucosyltransferase (GlcT-1) catalyzes the initial
glycosylation step of glycolipid biosynthesis.
Synthesis of GlcCer occurred at the cytosolic side of
the Golgi membrane, while other glycosylation
enzymes involved in glycolipid synthesis take place at
the lumenal side of the membrane.
GlcCer once formed must be translocated to the
lumenal side of the Golgi apparatus for further
glycosylation. Translocation of GlcT-1 is presumably
facilitated by a protein factor, flippase.
Sulfate groups are added last by a sulfotransferase
using PAPS (3'-phosphoadenosine-5'-phosphosulfate).
36. Synthesis of Cerebrosides
Ceramide is converted to glucosylceramide (GlcCer)
by Glucosylceramide synthase (GCS) and
Glucosyntransferase I.
Ceramide Glucosylceramide
Subsequently, GlcCer is converted to
lactosylceramide (LacCer) by β-(1,4) transfer of
galactose from UDP-galactose by
Galactosyltransferase I.
Glucosylceramide lactosylceramide
LacCer provides the common substrate for the
synthesis of more complex GSL.
37.
38.
39.
Glycosphingolipids are degraded by
lysosomal hydrolysis
The mixture of glycosphingolipids delivered to
the lysosomes for degradation will depend on the
cell type and its function: for instance,
Gangliosides will predominate in neurones
because of their abundance in the plasma
membrane of neurones
Red cell membrane glycolipids will be degraded
in the lysosomes of phagocytic macrophages.
40. The first stage is the step-wise removal of
monosaccharides by exoglycosidases from the
non-reducing ends of the glycan moieties, while
they are still attached to ceramide .
Subsequently, the pathways for the different
classes of glycosphingolipids converge on
lactosylceramide and, ultimately, ceramide, which
is degraded to sphingosine.
The catabolism of sphingolipids, is ensured by
their sequential degradation by a series of
hydrolases found within lysosomes.
41. The following figure shows several of the pathways and
intermediates in glycosphingolipid metabolism. The
breakdown deficiency of the lysosomal hydrolase, α-
galactosidase A is marked in the Globotriaosylceramide
and Digalactosylceramide.
42. The enzymes responsible for the
catabolism of glycosphingolipids are
typical lysosomal hydrolases with acidic
pH optima
Whereas the synthesis of glycosphingolipids
is mediated by membrane-bound enzymes,
the catabolism of membrane-bound
glycosphingolipids is brought about by soluble
hydrolases in the lumen of Iysosomes.
Nature has developed two strategies for
coping with this heterologous system:
association of the enzymes with the
lysosomal membrane; and the use of non-
enzymic protein detergents and cofactors.
Glycosphingolipids are eventually broken
down to their individual components, which
are then available for reuse.
43. α-galactosidase A (ceramide-trihexosidase,
GLA) is a glycoside hydrolase enzyme that
hydrolyses the terminal alpha-galactosyl
moieties from glycolipids and glycoproteins
Glycosphingolipid storage diseases are rare genetic
disorders that lead to the accumulation of
glycosphingolipids in lysosomes.
They typically result from mutations in
glycosidases.
The sphingolipidoses are a series of diseases in
which mutations affecting the enzymes catalysing
the last 11 steps of this process causing abnormal
compounds proximal to the metabolic block to
accumulate intralysosomally.
44. The degradation of sphingolipids containing three
or less carbohydrate residues requires a
sphingolipid activator protein and mutations
affecting these proteins also cause abnormal
glycosphingolipid storage. With one exception
(Fabry disease, which is X linked) the
sphingolipidoses are inherited autosomally.
45.
46. The biosynthesis of sphingolipids takes place in four
stages: -
1 )Synthesis of the 18-carbon amine sphinganine from palmitoyl-
CoA and serine;
2) Attachment of a fatty acid in amide linkage to yield N-
acylsphinganine;
3) Desaturation of the sphinganine moiety to form N-
acylsphingosine (ceramide); and
4)Attachment of a head group to produce a sphingolipid such as
a cerebroside or sphingomyelin.
The pathway shares several features with the pathways
leading to glycerophospholipids :NADPH provides reducing
power, and fatty acids enter as their activated CoA
derivatives.
In cerebroside formation, sugars enter as their activated
nucleotide derivatives. Head-group attachment in
sphingolipid synthesis has several novelaspects .
Phosphatidylcholine , rather than CDP-choline,serves as
47. In glycolipids, the cerebrosides and gangliosides
the head-group sugar is attached directly to the C-
1 hydroxyl of sphingosine in glycosidic linkage
rather than through a phosphodiester bond. The
sugar donor is a UDP-sugar (UDP-glucose or
UDPgalactose.
In animals, a double bond is created by a mixed-
function oxidase, before the final addition of a head
group: phosphatidylcholine, to form
sphingomyelin.
Sphingolipids are complex lipids whose core
structure is provided by the longchain:-
Amino alcohol sphingosine .
(4sphingenine trans1,3didroxy2amino4octadecene
48.
49. Palmitoyl CoA and serine condense to form 3-
ketosphinganine, which is reduced to
dihydrosphingosine before conversion into
ceramide ,a lipid consisting of fatty acid chain
attached to the amino group of a sphingosine
backbone .
The enzyme catalyzing this reaction requires
pyridoxal phosphate , revealing again the dominant
role of this cofactor in transformations that include
amino acids .
In all sphingolipids, the amino group of ceramide is
acylated .The terminal hydroxyl group also is
substituted .
50.
51. Sphingomyelin is part of the myelin sheath of nerve
fibers.
They are formed when ceramides reacts with
phosphatidylcholine to form spingomyelin plus
diacylglycerol .
This occurs mainly in the Golgi apparatus and to a
lesser extent in the plasma membrane.
52. Cerebrosides is the common name for a group
of glycosphingolipids called
monoglycosylceramides which are important
components in animal muscle and nerve cell
membranes.
The biosynthesis of monoglycosylceramides requires a
direct transfer of the carbohydrate moiety from a sugar-
nucleotide, such as uridine 5-diphosphate(UDP)-
galactose, or UDP-glucose to the ceramide unit.
The glycosyl-transferase catalyzed reaction results in
an inversion of the glycosidic bond stereochemistry,
changing from α →β.
Synthesis of galactosylceramide, and glucosylceramide
occurs on the lumenal surface of the endoplasmic
reticulum, and on the cytosolic side of the early Golgi
54. A ganglioside is a molecule composed of
a glycosphingolipid (ceramide and oligosaccharide)
with one or more sialic acids(e.g. n-
acetylneuraminic acid, NANA) linked on the sugar
chain.
Gangliosides are synthesized from ceramide by the
stepwise addition of activated sugars (eg, UDPGLc
and UDPGal) and a sialic acid , usually N-acetyl-
neuraminic acid .
56. Most cells continually degrade and replace their
membrane lipids.
For each hydrolyzable bond in a
glycerophospholipid,there is a specific hydrolytic
enzyme in the lysosome.
Phospholipases of the type remove one of the two fatty
acids, producing a lysophospholipid.
Lysophospholipases remove the remaining fattyacid.
Gangliosides are degraded by a set of lysosomal
enzymes that catalyze the stepwise removal of sugar
units,finally yielding a ceramide.
A genetic defect in any of these hydrolytic enzymes
leads to the accumulation of gangliosides in the cell,
with severe medical consequences.
57.
58. 1) It is the back bone upon which further
complexity is achieved. Phosphorylation of the c-
1 hydroxyl group yield the final breakdown
product and important molecule sphingosine-1-
phosphate, phytophingosine-1-phosphate and
dihydrsphingosine-1-phosphate.
2) Acylation of sphingosine, phytosphingosine, or
dihydrosphingosine with one of several possible
acyl CoA molecules through the action of distinct
ceramide synthases produce the molecule
defined as ceramide phytoceramide or
dihydroceramide.
3) Ceramide due to different acyl CoAs use to
produce, technically class of molecule to rather
than a single molecule and have different acyl
chain.
59. 4) The Glucosphingolilipids are divided :-
i) Glucosphingolipids
ii) Galactosphingolipids
Glucosphingolipids depend on enzyme
glucosylceramide synthatase which attach Glucose as
athe first residue from galactosylceramide synthatase
.glycosphingolipids is further devided glycotransferases
which increases the potential in lipid.
Whoever they can define phosphocholine headgroup
rather than addition of sugar residue sphingomyelin
headgroup , as they produce from a variety of ceramied
spices and can have differing acly chain.
The simple sphingolips serve as precursor and the
breakdown product of more than one complex.
Sphingolips have significant signaling and regulatary
roles in the cell.
In addition to major the level of simple Sphingolips
therefore become the focus of even more intense of
study in reset years.
