This document discusses compound lipids, which are esters of fatty acids combined with other groups in addition to an alcohol. Examples of compound lipids include phospholipids, glycolipids, and sphingolipids. Phospholipids contain a glycerol backbone, fatty acids, and a phosphate group attached to a nitrogenous base. Common phospholipids are phosphatidylcholine (lecithin), phosphatidylethanolamine, and phosphatidylserine. Glycolipids contain a carbohydrate, while sphingolipids are based on the alcohol sphingosine. Gangliosides are complex sphingolipids found abundantly in brain tissue.

1. Compound Lipids

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

3. 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)

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

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

6. 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.

7. Phospholipids

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

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

10. Phospholipids

11. 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

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

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

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

15. 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

16. Glycerphophatides

17. 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

18. 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
Phosphatidylcholine (Lecithin)

19. On hydrolysis yields
– Glycerol
– FA
– Phosphoric acid
– Nitrogenous base choline
Phosphatidylcholine (Lecithin)
Phosphatidylcholine (Lecithin)

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

21. 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

22. 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

23. 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

24. • 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.

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

26. 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.

27. 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)

28. 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

29. Phosphatidyl Inositol (PI)

30. 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)

31. 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

32. 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

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

34. 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.

35. 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

36. Functions of Phospholipids

37. 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

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

39. 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

40. 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.

41. 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.

42. Glycolipids

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

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

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

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

47. Glycosphingolipids

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

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

50. 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.

51. Oxynervon
Cerebron

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

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

54. 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)

55. GANGLIOSIDES

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

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

58. 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’).

59. GANGLIOSIDES
FA sphingosinecarbohydrate

60. GANGLIOSIDES
Ceramide

61. 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.

62. 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.

63. 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

64. 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.

65. 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.

66. 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

67. SULPHOLIPIDS

68. 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.

69. 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.

70. 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.

71. 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. ]

72. 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)

73. 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

74. 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

75. 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.

76. Examples of Spingiolipidoses

77. Flow chart

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

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