Compound lipids

SIMS 305- Clinical Biochemistry
Lipids
Dr. Ali Raza
Centre for Human Genetics and Molecular Medicine (CHGMM),
Sindh Institute of Medical Sciences (SIMS), SIUT.

Compound lipids
Esters of fatty acids containing other groups or in
addition to an alcohol and fatty acids.
FA + Alcohols + X (other group)
FA + glycerol / other alcohol + other group
(phosphoric acid/ nitrogenous base)
FA + Alcohols + X (Phosphoric acid)

Examples of Compound lipids:
Phospholipids
Glycolipids
Sulfolipids
Aminolipids / Proteolipids
Lipoprotein

Phosphatidic Acid and Phosphatidyl Glycerol
 Intermediate in the synthesis of TG and phospholipids
Phosphatidic Acid

Glycerphophatides (Phosphoglycerides)
 Glycerol is alcohol
 Glycerol-3-phosphate backbone
O P O
O
O
H2C
CH
H2C
OCR1
O O C
O
R2
phosphatidate
 fatty acids are esterified to hydroxyls on C1 & C2
 the C3 hydroxyl is esterified to Pi.

Phospholipids
Lipid contains
Fatty acid
Glycerol
Phosphoric acid
Nitrogenous base

Example of Phospholipids
 Phosphatidyl choline (Lecithin)
 Phosphatidyl ethanolamine (Cephalin)
 Phosphatidyl inositols (Lipositols)
 Phosphatidyl serine
 Plasmalogens
 Sphingomelins

Phospholipids
 Celmer and Carter classified based on type of alcohols in
phospholipids
• Glycerphophatides: Glycerol is alcohol
• Phospho-inositides: Inositol is alcohol
• Phospho-Sphingosides: Sphingol /Sphingosine is an
alcohol

Glycerol
Commonly called Glycerin
Trihydric alcohol contain 3-OH groups in the molecules
Colorless oily fluid with a sweetish taste
Glycerol

Inositol
 Inositol is an alcohol
 Hexa Hydroxyl Cyclohexane with M. Formula C6H12 O6

Sphingosine or sphingol
 Unsaturated Amino-alcohol
 Present in body as a constituent of
 Phospholipid
 Glycolipids

Examples of Phospholipids
 Glycerphophatides: Glycerol is alcohol
E.g. :Lecithin
Cephalin
Plasma login
 Phospho-inositides: Inositol is alcohol
E.g. phosphatidyl inositol
 Phospho- Sphingosides: Sphingosine is an alcohol
E.g. Sphingomyelin

X= Choline as polar head group
O P O
O
O
H2C
CH
H2C
OCR1
O O C
O
R2
CH2 CH2 N CH3
CH3
CH3
+
phosphatidylcholine
Phosphatidylcholine (Lecithin)
Choline

Structural and Metabolic function
Common membrane lipid
Source : Seeds and sprouts
Found in animals ( liver, brain, nerve tissues, sperm, yolk)
α and β lecithin are found depending on the position of
phosphoric acid choline complex

On hydrolysis yields
– Glycerol
– FA
– Phosphoric acid
– Nitrogenous base choline

• Chemical properties
• Lecithin (Acid, H2SO4 ) Choline + Phosphatidic acid
• Lecithin (boiled with alkali and mineral acids)
Glycerphophoric acid + 2 ( FA) + Choline

Phosphatidyl Ethanolamine / Cephalin
 Structure is same as lecithin
except ethanolamine replaces
choline
 α Cephalin
 β Cephalin
Brain and nerve tissues are rich
Phosphatidyl Ethanolamine / Cephalin

Phosphatidyl Serine
 A cephalin like phospholipid
 Contains amino acid serine in place of ethanolamine
found in brain and nervous tissues
 blood
 other tissues.
Phosphatidyl Serine

Phospholipase
• Phospholipase hydrolyze phospholipids
Types:
• A (A1) : found in humans and other mammalian tissues.
Isolated from Cobra Venom
• A2: found in human
• B: found in association with A , isolated from fungus
• C : found in Human and Plants. Brain and certain venom
• D : found in Plants; cabbage, cotton seeds and carrots

• specific site of action
Phospholipase
•A1: Attacks ester bond in position α (1)
of phospholipid.
•A2: ‘β’ position
• B: α position and lysolecithin
• C: Hydrolyses phosphate ester bond
•D: Splits off choline and phosphatidic
acid is formed.

Lysophosphatides
 Phosphoglycerides contains only one acyl radical in
α position
E.g. lysolecithin.

Specific site of action
Phospholipase
•A2: Attacks ‘β’ position and
• form Lysolecithin + one mol. fatty acid.
• B: Attacks lysolecithin and hydrolyses ester
bond in α position and forms
glyceryl phosphoryl choline + 1mol. fatty acid.
• C: Hydrolyses phosphate ester bond and
produces
α, β-diacyl glycerol and
phosphorylcholine.
•D: Splits off choline and phosphatidic acid is
formed.

Plasmalogens
 10 % of total phospholipids of brain and nervous tissue,
muscle and mitochondria.
on hydrolysis
(a) one molecule each of long chain aliphatic aldehyde
(b) fatty acids
(c) glycerol –PO4
(d) a nitrogenous base
(ethanolamine or choline)

Phosphatidyl Inositol
 Inositol is an alcohol
 hexa hydroxyl cyclohexane with M. Formula C6H12 O6
 Replace base choline of lecithin
O P
O
O
H2C
CH
H2C
OCR1
O O C
O
R2
OH
H
OH
H
H
OHH
OH
H
O
H OH
phosphatidyl-
inositol

Phosphatidyl Inositol
Found in brain, nervous tissues
Soybean, plant phospholipids
 In addition to being a membrane lipid,
has roles in cell signaling.
 Found in Acid fast bacilli (TB)

Sphingomyelins (Phosphatidyl sphingosides)
Does not contain Glycerol.
Contains an 18 carbon unsaturated amino alcohol called
‘sphingosine’ (sphingol).
Found in large quantities in brain and nervous tissues, and
very small amount in other tissues.
Sphingomyelins

Sphingomyelins (phosphatidyl sphingosides)
• On hydrolysis:
• Sphingomyelin yields
– one molecule of fatty acid
– phosphoric acid
– nitrogenous base choline
– one molecule of complex unsaturated amino alcohol
sphingosine (sphingol).
Sphingomyelins

Sphingomyelins (phosphatidyl sphingosides)
Sphingomyelinase is the enzyme which hydrolyses
sphingomyelin to form
Ceramide
Phosphoryl choline
Sphingomyelins

Sphingomyelins (Phosphatidyl sphingosides)
lipid-storage disease (lipidoses).
Niemann-Pick disease:
• inherited disorder of sphingomyelin metabolism in
which sphingomyelin is not degraded, as a result
sphingomyelin accumulates.

Cardiolipin
Found in mitochondria (inner membrane)
and bacterial wall.
• Diphosphatidyl glycerol.
• Hydrolysis:
4 mols of fatty acids
2 mols of phosphoric acid
3 mols of glycerol
only phosphoglyceride that possesses Antigenic properties

Functions of Phospholipids
Structural: as lipoprotein complexes which are thought to
constitute the matrix of cell walls and membranes,
E.g.: Mitochondria and Microsomes
Role in enzyme action:
Enzymes require tightly bound phospholipids for their actions.
E.g. Mitochondrial enzyme system involved in
oxidative phosphorylation

Role in electron transport
 PL help to couple oxidation with phosphorylation and
maintain electron transport enzymes in active
conformation and proper relative positions.

Structure: Constitute the Myelin Sheath of
Nervous system
Insulation: Phospholipids of myelin sheaths provide
the insulation around the nerve fibres.
The Myelin sheath, Nervous system

Role in lipid absorption in intestine:
• Lecithin lowers the surface tension of water and
• Aids in emulsification of lipid water mixtures
Role in transport of lipids from intestines:
• Exogenous TG is carried as lipoprotein complex,
chylomicrons, in which PL takes an active part.
Role in transport of lipids from liver:
• Endogenous TG is carried from Liver to various tissues
as lipoprotein complex Pre-β-lipoprotein (VLDL),
• PL is required for the formation of the lipoprotein
complex.

Role in blood coagulation:
PL an essential part in the blood coagulation process.
Required at the stage of:
1- Conversion of prothrombin to thrombin
by active factor X
2-In the activation of factor VIII
by activated factor IX.

Glycolipids
 lipids contains Carbohydrates
 Contains alcohol (sphingosine or sphinogol) and
nitrogenous base in addition to fatty acid
 Phosphoric acid and Glycerol are absent

Glycolipids
 found in the outer leaflet of the plasma membrane
bilayer with their sugar chains extending out from the
cell surface.

Glycolipids
 White and Grey matter of brain
 Myelin Sheaths of Nerve
 Membrane binding sites (receptor sites) for
hormones
Gaucher’s Disease

Glycolipids
Two types of Glycolipids
 Cerebrosides
 Gangliosides
• Collectively called Glycosphingolipids

Cerebrosides
 large amounts in the white matter of brain and
In the Myelin sheaths of nerve.

Cerebroside
on hydrolysis, yields:
• A sugar, usually Galactose, but sometimes Glucose
• A high molecular weight fatty acid
• Alcohol, sphingosine

Types of Cerebrosides
Cerebrosides are differentiated by the kinds of fatty acids in
the molecule.
Kerasin: Lignoceric acid (C23H47COOH) as FA
Cerebron (Phrenosin): hydroxy lignoceric acid
(Cerebronic acid)
 Nervon (Nervonic acid): Unsaturated homologue of
lignoceric acid (C23H45 COOH).
Oxynervon: hydroxy derivative of nervonic acid.

Cerebrosides
 β-Glucocerebrosidase, a lysosomal enzyme.
Glucocerebrosides Ceramide + glucose
β-Glucocerebrosidase

Cerebrosides
 In absence of the enzyme, glucocerebrosides (kerasin)
accumulate in reticuloendothelial (RE) cells viz., liver, spleen,
bone marrow and also brain.
Ceramide
Glucose

Cerebrosides
 Gaucher’s Disease:
Enzyme deficiency: β-Glucocerebrosidase
 Inherited disorder of cerebrosides metabolism (lipidosis)
 Major signs and symptoms include
enlargement of the liver and spleen(hepatosplenomegaly)
A low number of red blood cells (anemia)

GANGLIOSIDES
 The highest concentrations are found in Gray matter of
brain.
 Isolated from ganglion cells, neuronal bodies and
dendrites, spleen and RBC stroma.

GANGLIOSIDES
 The most complex lipid of the glycosphingolipids.
 They are large complex lipids, their molecular weights
varies from 180,000 to 250,000

GANGLIOSIDES
 • A long chain FA (usually C18 to C24).
• Alcohol-sphingosine.
 A carbohydrate moiety which usually contains:
– Glucose (Glc) and/or Galactose (Gal),
– One molecule of N-acetyl galactosamine,
– At least one molecule of N-acetyl neuraminic acid
(NANA) (also called ‘sialic acid’).

GANGLIOSIDES
FA sphingosinecarbohydrate

GANGLIOSIDES
 Brain gangliosides are known to be complex
 Contain 1 to 3 sialic acid residues [mono-(M) , di-(D),
trisialogangliosides(T)]
 The letter G refers to ganglioside, and
M is for Monosialic acid (one sialic acid)
 GM (Mono sialodi hexosyl ganglioside) is a type of
ganglioside.

Types of Gangliosides
 30 types of gangliosides have been isolated from brain
 Four important types are: GM-1, GM-2, GM-3 and GD-3.

Types of Gangliosides
 GM3 :
• The simplest and common ganglioside found in tissues
 GM3 contains
 one molecule of galactose
 one molecule of neuraminic acid (NeuAc)
 one molecule of glucose and
 Ceramide

GM1 -- Clincal Importance
 GM1 is a more complex ganglioside derived from Gm3
 The gangliosides can serve as specific membrane binding
sites (receptor sites) for circulating hormones
 Thereby influence biochemical processes in the cell.
 Known to be the receptor in human intestine for cholera
toxin.

Clincal Importance
GM1 Gangliosidosis
 The inheritance pattern and symptoms are similar to
Tay-Sach’s disease.
 Due to a deficiency of the enzyme β-galactosidase,
 Results in accumulation of
 GM1 gangliosides,
 Glycoproteins and
 the mucopolysaccharide karatan sulphate.

Tay-Sachs Disease (GM2 Gangliosidosis)
 Normal degradation of GM2 requires hexosaminidase A
 Removes the terminal Gal-NAc.
 Subsequently the other components are hydrolysed by
other specific enzymes.
 In absence Hexosaminidase A, GM2 cannot be degraded
and accumulates in brain and nervous tissues

SULPHOLIPIDS(Sulfatide /Sulfoglycolipids)
 Lipids material containing sulphur
 In general, they appear to be sulfate esters of glycolipids,
the sulphate group is esterified with OH gr. of hexose
moiety of the molecule.

SULPHOLIPIDS
 found in liver, kidney, testes, brains and certain tumours.
 Most abundant in white matter of brain.
 Several types of sulfur containing lipids have been isolated
from brain and other tissues.

Sulpholipids: Clinical significance
 Sulphatide is formed from ‘galactocerebroside’ through
esterification of OH group on C3 of galactose with H2SO4
(SO4 at C3 of Gal).
Ratio of cerebroside: to sulphatide in brain normally is 3:1.

Sulpholipids: Clinical significance
1-Metachromatic Leucodystrophy (MLD)
 Enzyme sulphatase called as Aryl sulfatase A
 Ratio of cerebroside: to sulphatide in brain altered to 1:4.
 Deficiency of Sulphatase causes Metachromatic
Leucodystrophy (MLD) [sulfatide accumulates in
various tissues. ]

2. Fabry’s disease
 An inherited disorder, a lipid storage disease (lipidosis).
 Enzyme deficiency: α-galactosidase.
Found in liver, spleen, kidney, brain and small intestine.
 Nature of lipid that accumulates ceramide trihexoside
(globotriosyl ceramide)

Fabry’s disease
• Clinical manifestations:
Vascular thrombosis: Lipid accumulates in the
endothelial lining of blood vessels
Renal failure– extensive deposition of lipids in
glomeruli.
Cardiac enlargement
Eye involvement: cataracts, vascular dilatation

3. Krabbe’s Disease
 An inherited disorder, a lipid storage disease (lipidosis).
 Enzyme deficiency: β-galactosidase (Galactocerebrosidase).
 The enzyme normally catalyzes the hydrolysis of galactocerebrosides
and it splits the linkage between ceramide and galactose
 Nature of lipid accumulating: Galactosyl ceramide

3. Krabbe’s Disease
 Clinical manifestations:
 Severe mental retardation in infants
 Total absence of myelin in central nervous system
Globoid bodies found in white matter of brain.

Component Disease
name
Enzyme
deficiency
Causes
Cholesterol
Sphingomyelin
Sulpholipids
Cerebrosides
Gangliosides
Assignment

79
Reference:
Textbook Medical Biochemistry by Chatterjea,
Sixth Edition, Chapter 4
https://www.amazon.com/Textbook-Medical-Biochemistry-M-D-
Chatterjea/dp/9350254840

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