This presentation shows the classification and occurrence of human lipids and their biological value. It also reveals the chemical formula of human lipids

2. Lipid Chemistry and Metabolism
By
Professor Ayman Barghash
Mediccal Biochemistry
Faculty of Medicine
Alexandria University

3. Lipids

4. Lipids

5. Lipid Chemistry
and
Metabolism

6. Definition of Lipids
Lipids are a heterogeneous group of water insoluble
organic molecules, that can be extracted from
tissues by non polar solvents.

7. Common Properties of Lipids
1. Relatively insoluble in water.
2.Soluble in nonpolar solvents (fat solvents) as
ether, chloroform, benzene and acetone.
3.Can be utilized by living organisms.
4. Contain fatty acids (FAs) or derived from FAs.

8. Biomedical Importance of Lipids
1. Important source of energy (oxidation of 1 g of fat
yields 9.3 Kilocalories)
2. Protective coating around certain organs to
keep them in position e.g. peri-nephric fat.
3. Thermal insulator e.g. subcutaneous fat.
4. Electrical insulator e.g. fat of the myelin sheath.

9. Myelin Sheath
.
Cell body
Axon
Nerve terminal
Myelin
sheath
Myelin sheath

10. Biomedical Importance of Lipids (cont.)
5. Prostaglandins, some hormones e.g. steroid
hormones (such as testosterone, estrogen,
progesterone and cortisol) are lipids in nature.
6. Fat-soluble vitamins (K, E. D. and A) are essential
for good health and growth.
7. Cholesterol, phospholipids and glycolipids are
structural components of membranes.

11. Biomedical Importance of Lipids (cont.)
8. Bile salts are derived lipids that help the digestion
and absorption of lipids.
9. Lipoproteins (complexes of lipids and proteins)
are important cellular constituents ( e.g. cell
membrane) and help the transport of lipids in
plasma.

12. Source
of energy
Protection & components
of cell membrane
Thermal & Electrical
insulator
Hormones
Prostaglandins
Lipoproteins
Bile salts
Fat-soluble
vitamins
Biomedical Importance of Lipids
Importance
of
Lipids

13. Classification of Lipids
I
Simple Lipids
III
Derived Lipids
II
Complex
Lipids
FA + Alcohol
FA + Alcohol + Other groups
e.g. Phosphate, CHO or proteins
Derived from I & II
e.g. FAs, alcohols, steroids,
carotenoids, and fat-soluble
vitamins

14. I. Simple Lipids
They are esters of fatty acids (FAs) with alcohol.
N.B.
An ester is the product of reaction between an
acid and an alcohol.
Acid + alcohol Ester

15. Classification of Simple Lipids
True Fat Wax
Ester of FA + Glycerol
(trihydic alcohol)
Ester of FA + higher
monohydic alcohols
Liquid or solid at room
temperature
Solid at room
temperature
Can be utilized by
humans
Can not be utilized by
humans

16. Glycerol
Properties
1. Colorless liquid
2. Sweet
3. Hygroscopic
CH2-OH
HO-CH
CH2-OH
Glycerol
(Trihydric alcohol)
2
1
3

17. True Fat (Neutral fat)
They are estrs of fatty acids with glycerol
CH2-OH
HO-CH
CH2-OH
Glycerol
R-C-OH
Fatty acid
O
OH-C-R
Fatty acid
O
OH-C-R
Fatty acid
O
3 H2O
1
3
2

18. Structure of Triacylglycerol (Triglyceride)
O
CH2-O-C-R
O Acyl group
R-C-O-CH
Acyl group O
CH2-O-C-R
Acyl group
Triacylglycerol
2
1
3

19. Types of Acylglycerol
1. Monoacylglycerol
 It contains one acyle group linked to either C1 or
C2, so there may be:
 1- monoacylglycerol
 2- monoacylglycerol.

20. 1-Monoacylglycerol
O
CH2-O-C-R
Acyl group
HO-CH
CH2-OH
1-monoacylglycerol
1
2
3

21. 2-Monoacylglycerol
CH2-OH
O
R-C-O-CH
Acyl group
CH2-OH
2-monoacylglycerol
2
1
3

22. Types of Acylglycerol (cont.)
2. Diacylglycerol
It contains 2 acyle groups linked to either C1 and C2,
or C1 and C3 so there may be:
 1,2-diacylglycerol
 1,3-diacylglycerol.

23. 1,2-Diacylglycerol
O
CH2-O-C-R
O Acyl group
R-C-O-CH
Acyl group
CH2-OH
1,2-diacylglycerol
2
1
3

24. 1,3-Diacylglycerol
O
CH2-O-C-R
Acyl group
HO-CH
O
CH2-O-C-R
Acyl group
1,3-Diacylglycerol
2
1
3

25. Types of Acylglycerol (cont.)
3. Triacylglycerol
Contain 3 simlar or different FAs., so there may be:
 Simple triacylglycerol
The 3 FAs are the same e.g. tripalmitin, tristearin
and triolein. Tripalmitin contain 3 molecules of
palmtic acid.

26. Simple Triacylglycerol; Tripalmitin
O
CH2-O-C-(CH2)14-CH3
O Palmitoyl group
CH3-(CH2)14-C-O-CH
Palmitoyl group O
CH2-O-C-(CH2)14-CH3
Palmitoyl group

27. Types of Acylglycerol (cont.)
 Mixed triacylglycerol
It contains 2 or 3 different FAs e.g.
1,3-dipalmitoyl, 2-Stearin
1-palmitoyl, 2-stearoyl, 3-olein

28. Mixed Triacylglycerol;1,3-dipalmitostearin;
1,3-dipalmityl-2-stearyl glycerol
O
CH2-O-C-(CH2)14-CH3
O Palmitoyl group
CH3-(CH2)16-C-O-CH
Stearyl group O
CH2-O-C-(CH2)14-CH3
Palmitoyl group
1
3
2

29. Mixed Triacylglycerol; 1-palmityl, 2-stearyl, 3-
olein; 1-palmityl, 2-stearyl, 3-oleyl glycerol
O
CH2-O-C-(CH2)14-CH3
O Palmitoyl group
CH3-(CH2)16-C-O-CH
Stearoyl group O
CH2-O-C-(CH2)7- CH=CH-(CH2)7-CH3
Oleoyl group
1
3
2

30. Fatty Acids (FAs)
• They are aliphatic monocarboxylic organic acids
from 2 -24 carbons
• General formula
O O
R-C-OH or CH3-(CH2)n-C-OH
• Example: Butyric acid
CH3- CH2- CH2 - COOH
CH3 - (CH2)2 - COOH

31. Ionization of Fatty Acids
CH3 – (CH2)2 – COOH
CH3 – (CH2)2 – COO- H+
Ionization (at physiological pH)
Fatty acid e.g. butyric acid
Butyrate Proton
H+
COO

32. General Structure of a Fatty Acid
 Fatty acids are amphipathic molecules composed of
a hydrophilic (polar, ionized) head (formed by the
carboxyl group) and a hydrophobic (non-polar,
non-ionized) tail (formed by the hydrocarbon chain).
 The degree of solubility of a fatty acid depends on
the length of the hydrocarbon chain.

33. Fatty Acids are Amphipathic Molecules
CH3 - (CH2)n – COO
Hydrocarbon chain Carboxyl group
Tail Head
Hydrophobic Hydrophilic
Water-insoluble Water-soluble
Non-ionized Ionized
Non-polar Polar

34. N.B.
The degree of solubility of a fatty acid depends on
the length of the hydrocarbon chain.

35. Fatty Acids are Amphipathic Molecules
.
Hydrophilic head
Hdyrophobic tail
Carboxylic group
Hdyrocarbon chain

36. Numbering of Fatty Acid Carbons
ω (n)
CH3 – CH2 - CH2 - COOH Butyric acid
4 3 2 1 Arabic numbers
   Greek alphabetical letters
1 2 3 4 Omega numbers

37. Classification of Fatty Acids
1. According to chain length
(short, medium & long)
2. According to saturation
(saturated & unsaturated)
3. According to Biological value
(essential & non-essential)

38. Classification of FAs According to Chain
Length
1. Short chain (Low) fatty acids
Contain less than 10 carbon atoms (i.e. from 2 – 8
carbon atoms)
Acetic acid (2 C): CH3-COOH
Butyric acid (4 C): CH3-CH2-CH2-COOH
2. Medium chain (medium) fatty acids
Contain from 10 – 12 carbon atoms

39. Classification of FAs According to Chain
Length (cont.)
3. long chain (High) fatty acids
Contain < 12 carbon atoms
Palmitic acid (16 C): CH3-(CH2)14-COOH
Stearic acid (18 C): CH3-(CH2)16-COOH

40. Classification of FAs According to Saturation
Unsaturated FAs
(contain one or more double bonds)
Saturated FAs
(contain no double bonds)
Monounsaturated FAs
(contain one double bond)
Polyunsaturated FAs
(contain more than one double bond)

41. Examples of Saturated Fatty Acids
1. Butyric acid (4 C)
CH3-CH2-CH2-COOH
[ CH3-(CH2)2-COOH ]
2. Palmitic (16 C)
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH
[ CH3-(CH2)14-COOH ]
3. Stearic acid (18 C)
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH
[ CH3-(CH2)16-COOH ]
4
16
1
1
1
18

42. Dietary Sources of Saturated Fat
 Whole milk and other
high-fat dairy products
 Red meat, poultry skin
and lard
 Butter
 Tropical oils: coconut,
palm oil, palm kernel oil

43. Oleic acid
Symbol (18 : 1 ; 9 ) or ω9 (n9)
18 9 1
CH3- (CH2)7 - CH = CH - (CH2)7 - COOH
ω (n) 9
Example of Monounsaturated (Monoenoic)
Fatty Acids (MUFA)
Number of carbons Position of the double bond
Number of double bonds

44. Dietary Sources of MUFA
 Olives and olive oil
 Peanuts and peanut oil
 Canola oil
 Avocados
 Most nuts

45. 1. Dienoic fatty acids (contain 2 double bonds)
18 13 12 10 9 1
CH3 - (CH2)4 - CH = CH - CH2- CH = CH - (CH2)7 - COOH
Linoleic acid (18: 2 ; 9,12 ) ω6
2. Trienoic fatty acids (contain 3 double bonds)
18 16 15 13 12 10 9 1
CH3 - CH2 - CH = CH - CH2 - CH = CH - CH2 - CH = CH - (CH2)7 -COOH
CH3 - (CH2 - CH = CH)3 - (CH2)7 – COOH
α-Linolenic (18: 3; 9,12, 15) ω3
Examples of Polyunsaturated Fatty Acids
(BUFA)
ω 6
ω 3

46. N.B.
 α-linoleic acid (ALA) contains 18 carbon atoms
and has 3 cis double bonds at positions 9,12,15 so
it is an ω3 (or n-3) fatty acid.
 γ-linoleic acid (GLA) contains 18 carbon atoms
and has 3 cis double bonds at positions 6,9,12 so
it is an ω6 (or n-6) fatty acid.

47. 3. Tetraenoic fatty acids (contain 4 double bonds)
20 1
CH3 - (CH2)3 - (CH2 - CH = CH)4 - (CH2)3 – COOH
Arachidonic acid (20: 4; 5, 8, 11, 14) ω6
Examples of Polyunsaturated Fatty Acids
(BUFA) (cont.)
1
ω
5
8
14
11
20
6

48. Example of Unsaturated (Enoic) Fatty Acids
Unsaturated
fatty acid
No of
carbons
No of
Double
bonds
Position
of double
bonds
Symbol
Oleic acid 18 1 (Monoenoic) 9 18:1;9
(ω9)
Linoleic acid 18 2 (Dienoic) 9,12 18:2;9,12
(ω6)
α-Linolenic acid 18 3 (Trienoic) 9,12,15 18:3,9,12,15
(ω3)
Arachidonic acid 20 4 (Tetraenoic) 5,8,11,14 20:4;5,8,11,14
(ω6)

49. Dietary Sources of Linoleic Acid
(ω-6 fatty acids)
I. Nuts and seeds.
II. Some vegetables.
III. Vegetable oils:
 Soybean
 Safflower
 Corn

50. Cis and Trans Configurations of Unsaturated
FAs
C C
H H
C C
H
H
Cis - configuration of FAs
(The 2 H atoms are present on
one side of the double bond)
Trans - configuration of FAs
(The 2 H atoms are present on
opposite sides of the double bond)

51. Cis and Trans Fatty Acids
Cis fatty acid (kinked)
Trans fatty acid (straight shape)
Kink
Saturated bonds
Unsaturated cis bond
Straight
unsaturated trans bond
No kink (straight)

52. Cis Fatty Acids
 They have a bend or a kink at the point of double
bond in the fatty acid chain.
 Cis configuration is the most common form for an
unsaturated FA.

53. Trans Fatty Acids
 They have a straight shape similar to that of
saturated FAs.
 They occur naturally in dairy and other animal fats
and in some plants.
 They are produced commercially during the
hydrogenation process of unsaturated fat.

54. N.B.
 Lipids containing a high percentage of long chain
saturated fatty acids (FAs) have a higher melting
point than lipids containing a high percentage of
unsaturated FAs because saturated FAs are more
packed (unlike unsaturated FAs which are loose
due to the presence of a kink at the site of the

55. double bond), and are held together by a large
number of Wander Wales interactions, so a large
amount of energy is needed to disrupt such
interactions to keep them in the liquid state.
Accordingly their melting point is higher than that
of lipids containing a high percentage of
unsaturated FAs.

56.  This explains why oils (that contain a high
percentage of unsaturated FAs) are liquid at room
temperature.

57. Packing of Fatty Acids into Stable Aggregates
Saturated Fatty Acid Cis-unsaturated Fatty Acid
Kink
Straight

58. Dietary Sources of α-Linolenic Acid
(ω-3 fatty acid)
I. Cold- water ocean fish such as:
 Mackerel
 Salmon
 Sardines
 Tuna

59. Dietary Sources of α-Linolenic Acid
(ω-3 fatty acid) (cont.)
II. Fish oils
 Especially from fatty fish.
III. Vegetable oils
 Soybean oil
 Flaxseed oil

60. Comparison of Dietary Fats

61. Classification of FAs According to Biological
Value
1. Essential Fatty Acids
They can not be synthesized by mammals and
must be obtained from plant sources. They are
polyunsaturated fatty acids.
e.g. Linoleic acid and α-linolenic acid.

62. 2. Non Essential Fatty Acids
•They can be synthesized by mammals, so it is not
essential to take them in diet.
•They include saturated fatty acids (e.g. palmitic
acid) and monounsaturated fatty acids (e.g. oleic
acid).
Classification of FAs According to Biological
Value (cont.)

63. 3. Relatively Essential Fatty Acids
•They can be synthesized by mammals from dietary
• precursors, so they become essential if their
• precursor is missed the from diet.
 Arachidonic acid is synthesized in the body from
linoleic acid, so it is a nonessential FA.
Classification of FAs According to Biological
Value (cont.)

64.  Arachidonic acid becomes essential if linoleic
acid is missed from the diet.
 Arachidonic acid is also found in animal fats and
peanut oil.
Classification of FAs According to Biological
Value (cont.)

65. Classification of FAs According to Biological
Value
Essential FAs Non Essential
FAs
Relatively
Essential FAs
Polyunsaturated FA
e.g. linoleic acid
α-linolenic acid
Saturated and mono-
unsaturated FA
e.g. palmitic acid
oleic acid
e.g. arachidonic acid

66. NB.
1. Mammals can synthesize saturated FAs and
monounsaturated FAs, but they are unable to
synthesize FAs containing more than one double
bond because they lack the enzyme system that is
responsible for introduction of a double bond
beyond carbon 10.

67. 2. Arachidonic acid contains 4 double bonds but it
can be synthesized in the human body from
linoleic acid, so it is a non-essential fatty acid.
Arachidonic acid becomes essential if linoleic acid
is missing in the diet. Arachidonic acid is also
found in animal fats and peanut oil.

68. 3. Arachidonic acid is a very important FA because it
is a source of prostaglandins, thromboxanes and
leukotrienes which perform very important
functions in the body.

69. Arachidonic Acid is a Relatively Essential
Fatty Acid
Linoleic acid
(Essential FA)
Prostaglandins
Thromboxanes
Leukotrienes
Diet
Diet Arachidonic acid
(non- essential FA)
In human body

70. Other Fatty Acids
1. Sulfur-containing fatty acids
2. Hydroxy faty acifds
3. Branched fatty acids

71. Sulfur-containing Fatty Acids
e.g. α- Lipoic acid (6,8 dithiooctanic acid)
CH2 - CH2 - CH - (CH)4 - COOH
S S
CH2 - CH2 - CH - (CH)4 – COOH
SH SH
2H

72. Sulfur-containing Fatty Acids
e.g. α- Lipoic acid (6,8 dithiooctanic acid)
(cont.)
Function
 It is a water-soluble vitamin that acts as a
hydrogen carrier and coenzyme in oxidative
decarboxylation of -keto acids e.g. pyruvate and
-ketoglutarate dehydrogenase complexes.

73. Hyroxy Fatty Acids
The hydroxyl group is attached to -carbon e.g.
1. Cerebronic acid (hydroxyl lignoceric acid)
- CH3-(CH2)21 -CHOH-COOH
2. Hydroxynervonic acid
CH3 -(CH2)7 -CH=CH-(CH2)12-CHOH-COOH
α
α

74. Branched Fatty Acids
- e.g. phytanic acid (3,7,11.15 tetra methyl palmitic
acid)
- phytanic acid is present in milk lipids and animal
fat.
3
7
11
15

75. Rancidity
Definition
Bad odor and taste of fat
Mechanism and types of rancidity
A) Hydrolytic rancidity
It is due to hydrolysis of fat with liberation of
volatile short chain fatty acids having bad odor and
taste.

76. Rancidity (cont.)
B) Oxidative rancidity
It is due to oxidation of the unsaturated fatty acids
in fat with the formation of peroxides and ketones
having bad odor and taste.
Factors causing rancidity
Exposure of fat to light, heat, moisture, or bacterial
action.

77. Rancidity (cont.)
Prevention of rancidity
1. keeping fat coverd in a cool dry place away from
light and moisture.
2. Addition of antioxidants e.g. vitamin A and E to
fat.

78. Biological Importance of True Fat
1. It is stored as depot fat in the subcutaneous
tissue and is mobilized during starvation to
produce energy and so its amount is variable,
thus, true fats are known as variable element of
fat.
2. It is the most compact form in which energy can
be stored (1 gm of fat  9.3 KCal).

79. Biological Importance of True Fat (cont.)
3. It forms a supportive and protective coating
around some organs in the body e.g. fat around
the kidneys.

80. II. Complex (Compound) Lipids
They are esters of fatty acids with alcohol and in
addition they contain other groups e.g.
1. Phospholipids
They contain phosphate group.
2. Glycolipids (Glycosphingolipids)
They contain carbohydrates.

81. II. Complex (Compound) Lipids (cont.)
3. Sulpholipids
They are glycolipids that contain sulphate groups.

82. 1. Phospholipids
Definition
They are amphipathic compounds composed of an
alcohol that is attached by a phosphodiester
bridge to either diacylglycerol or sphingosine.

83. 1. Phospholipids (cont.)
Classification
Phospholipids are classified according to the type of
alcohol they contain into:
A. Glycerophospholipids
They contain glycerol as a backbone.
B. Sphingophospholipids (Sphingomyelins)
They contain sphingosine as a backbone.

84. Classification of Phospholipids
(According to the Type of Alcohol They
Contain)
Sphingophospholipids
(contain sphingosine)
Glycerophospholipids
(contain glycerol)

85. Structure of Sphingosine
 Sphingosine is an amino alcohol composed of 18
carbon atoms.
 It contains two hydroxyl groups, one amino group,
and one double bond between C4 and C5.
CH3 - (CH2)12- CH = CH – CH – CH – CH2
OH OH
NH2
1
5 4 3 2
18

86. Phospholipids are Amphipathic Molecules
Phospholipids are amphipathic molecules i.e. each
molecule has a hydrophilic (polar) head (formed of
the phosphate group and the alcohol group) and a
hydrophobic (non-polar) tail (formed of glycerol or
sphingosine and the hydrocarbon chains of the
fatty acids).

87. Phospholipids are Amphipathic Molecules
.
Hydrophilic head
Hdyrophobic tail
Phospholipid molecule

88. Structure of Phospholipids
Glycerophospholipids
Consist of
Glycerol backbone
Linked to
±Alcohol
• Choline
• Serine
• Ethanol-
• amine
• Inositol
Two
fatty acids
Phosphate
Consist of
Sphingosine backbone
Linked to
Alcohol
• Choline
Phosphate
one
fatty acids
Sphingophospholipids
(Sphingomyelins)

89. Glycerophospholipids [3(α)-type)
CH2-O
O-CH
CH2-O
Glycerol
R-C -
Acyl group
O
- C-R
Acyl group
O
- P- OH
Phosphate group
O
± Alcohol
1
3
2
OH

90. Glycerophospholipids [2(β)-type]
CH2-O
O-CH
CH2-O
Glycerol
-C - R
Acyl group
O
- C-R
Acyl group
O
OH- P- O-
Phophate group
O
Alcohol±
1
3
2
OH

91. Alcohols of Glycerophospholipids
OH – CH2 – CH – NH3 Serine
OH – CH2 – CH2 – NH3 Ethanolamine
OH – CH2 – CH2 – N Choline
Inositol
COOH
CH3
CH3
CH3
CO2
3 CH3
OH
OH
OH
H
OH
H
OH
OH
H
H
H
H
1
2
3
4
5 6

92. Phosphodiester Bridge of
Glycerophospholipids
CH2-O
O-CH
CH2-O
Glycerol
R-C -
Acyl group
O
- C-R
Acyl group
O
- P -
Phosphate group
O
Alcohol
1
3
2
OH
Phosphodiester
bridge

93. Glycerophospholipids are Amphipathic
Molecules
O
CH2 - O - C- R
O
R-C - CH
CH2- O - P - O Alcohol
(base)
Diacylglycerol
Hydrophilic
Glycerol backbone
O
+
Acyl
groups
Hydrophobic
Phosphorylalcohol
O

94. Glycerophospholipids (Zwitterion Form)
CH2-O
O-CH
CH2-O
Glycerol
R-C -
Acyl group
O
- C-R
Acyl group
O
- P- O -
Phosphate group
O
Alcohol+
1
3
2
O-
Zwitterion

95. Types of Glycerophospholipids
There are several members of glycerophospholipids
according to the type of alcohol they contain:
1. Phosphatidic acid (does not contain alcohol)
2. Phosphatidyl choline (Lecithin), contains choline
3. Phosphatidyl ethanolamine (cephalin), contains
ethanolamine
4. Phosphatidyl serine, contains serine
5. Phosphatidyl inositol, contains inositol

96. Types of Glycerophospholipids (cont.)
6. Phosphatidyl glycerol
7. Cardiolipin (diphosphatidyl glycerol)
8. Plasmalogens
9. Platelet-activating factor (PAF)

97. N.B.
 Choline is a component of lecithin
(glycerophospholipid) and acetylcholine
(neurotransmitter).

98. Phosphatidic acid
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O -P-OH
O

99. Phosphatidylcholine (Lecithin)
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O-P - O-choline
O

100. N.B.
 An enzyme called lecithinase is prsent in the
venom of cobra. It splits the unsaturated FA from
lecithin of cell membrane of RBCs giving rise to
lysolecithin which causes hemolysis (lysis of red
cell membrane).

101. Dipalmitoylphosphatidylcholine (DPPC) in
lung surfactant
O
CH2-O-C-(CH2)14-CH3
O
CH3-(CH2)14-C-O-CH
O
CH2-O-P- O-choline
Palmitoyl
group
Glycerol backbone
O
Palmitoyl
group

102. Role of phosphatidylcholine in lung surfactant
 Dipalmitoyl phosphatidylcholine (DPPC , or
dipalmitoyl lecithin) contains the fatty acid
palmitate at positions 1 and 2 on the glycerol.
 DPPC is synthesized and secreted by type II
pneumocytes and is the major lipid component of
lung surfactant.

103. Role of phosphatidylcholine in lung surfactant
(cont.)
Lung surfactant is the extracellular fluid layer
lining the lung alveoli and is composed of a
complex mixture of lipids (90%) and proteins
(10%).
Lung surfactant decreases the surface tension of
this fluid layer, reducing the pressure needed to
reinflate lung alveoli, thereby preventing alveolar
collapse (atelectasis).

104. Lung surfactant
.
cells of the lung alveolus
Lung surfactant
air

105. Respiratory Distress Syndrome (RDS)
Cause
It is due to decreased lung surfactant in:
1. Preterm infants due to insufficient production and/
or secretion of lung surfactant . This represents a
significant cause of neonatal deaths in Western
countries.
2. Adults whose surfactant-producing pneumocytes
have been damaged or destroyed, for example, by
infection or trauma.

106. Respiratory Distress Syndrome (RDS) (cont.)
Features
t is characterized by lung collapse.
Diagnosis
 Lung maturity of the fetus can be measured by
determining the ratio of DPPC (lecithin) to
sphingomyelin (L/S ratio) in amniotic fluid.
 A ratio of two or more at about the 32th week of
gestation is an evidence of lung maturity.

107. Respiratory Distress Syndrome (RDS) (cont.)
Management
Acceleration of lung maturation by:
a. Giving the mother glucocorticoids shortly
before delivery or
b. Intratracheal instillation of natural or synthetic
surfactant.

108. Phosphatidylethanolamine (Cephalin)
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O -P-O-ethanolamine
O

109. Phosphatidylserine
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O -P-O-seine
O

110. Phosphatidylinositol
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O -P-O-inositol
O

111. Phosphatidylinositol (PI)
 PI is an unusual phospholipid in that it often
contains stearic acid on C1 and arachidonic
acid on C2 of the glycerol.
Function
1. It serves as a reservoir of arachidonic acid in
membranes which is a precursor for
prostaglandin synthesis.
2. It plays a role in membrane protein anchoring.

112. 3. Phosphatidylinositol- 4,5 biphosphate (PIP2) plays
a role in signal transmission across membranes.

113. Role of PI in membrane protein anchoring
- Specific proteins can be covalently attached via a
carbohydrate bridge to membrane-bound PI e.g.
alkaline phosphatase and acetylcholine esterase.
- A deficiency in the synthesis of glycosyl
phosphatidyl inositol in hematopoietic cells results
in a hemolytic disease called paroxysmal nocturnal
hemoglobinuria.

114. Role of PI in membrane protein anchoring
.
Anchored protein
e.g. ALP & acetylcholine
esterase
Carbohydrate bridge
Cytoplasm
PI
Extracellular space
Cell membrane

115. Role of PIP2 in signal transmission across
membranes
 Binding of a variety of neurotransmitters, hormones,
and growth factors to receptors on the cell membrane
causes degradation of PIP2 by phospholipase C into
inositol 1,4,5-trisphosphate (IP3) and diacylglycerol
(DAG).

116. Cleavage of phosphatidylinositol 4,5-bisphosphate
(PIP2) by phospholipase C (PLC)
Inositol
triphosphate
(IP3)
Diacylglycerol
(DAG)
P
P
5
4

117. Role of PIP2 in signal transmission across
membranes (cont.)
 IP3 and DAG mediate the mobilization of intracellular
calcium and the activation of protein kinase C (PKC)
respectively. These evoke specific cellular responses.

118. Role of PIP2 in signal transmission across
membranes
Outside of cell
Inside
of cell
Neurotransmitter,
hormone,
growth factors
Specific
cellular
responses
PIP2

119. Phosphatidylglycerol
O
CH2-O-C-R1
O
R2-C –O-CH
O
CH2-O -P-O-glycerol
N.B.
Phosphatidylglycerol is a component of cell
membrane.
O

120. Cardiolipin (diphosphatidyl glycerol)
- It is composed of two molecules of phosphatidic
acid connected by a molecule of glycerol.
Location
- It is abundant in the cardiac muscle.
- It is exclusive to the inner mitochondrial membrane
where it appears to be required for the mainten-
ance of certain complexes of the respiratory chain.

121. Cardiolipin (diphosphatidyl glycerol)
Glycerol
Phosphatidic
acid
Phosphatidic
acid

122. Importance
1. it appears to be required for the mainten-
ance of certain complexes of the respiratory chain.
2. It is used in the serological diagnosis of syphilis
(cardiolipin is antigenic, and is used for
detection of antibodies raised against the
bacterium that causes syphilis).

123. Plasmalogens
(Ether glycerophospholipids)
-The fatty acid at carbon 1 of a glycerophospho-
lipids is replaced by an unsaturated alkyl group
attached by an ether (rather than an ester) linkage
to the glycerol backbone.

124. Plasmalogens
CH2-O - CH CH-R1
O
R2-C - O-CH
O
CH2-O- P-O-choline
Ether bond
O
Unsaturated
alkyl group
Ester bond
or
ethanolamine
Glycerol backbone
Acyl group

125. Plasmalogens
(Ether glycerophospholipids) (cont.)
Examples
a. Phosphatidalcholine
It is similar to phosphatidylcholine.
It is abundant in heart muscle.
b. Phosphatidalethanolamine
It is similar to phosphatidylethanolamine.
It is abundant in nerve tissue.

126. Alkyl, acyl, and acetyl groups
.
CH3-(CH2)n- Alkyl (R) group
CH3-C- Acetyl group
R-C- Acyl group
R-O-R Ether
O
O

127. Platelet-activating factor (PAF)
 A saturated alkyl group is attached by an ether
linkage to carbon 1, and a acetyl group is linked
to carbon 2 of the glycerol backbone.

128. Platelet-activating factor (PAF)
CH2-O – CH2-CH2-R
O
CH3-C - O-CH
O
CH2-O- P-O-choline
O
saturated
alkyl group
Glycerol backbone
Acetyl group

129. Platelet-activating factor (PAF) (cont.)
Functions
1. It stimulates aggregation and degranulation of
platelets.
2. It mediates acute inflammatory and hyper-
sensitivity reactions.
3. It stimulates neutrophils and alveolar macro-
phages to generate superoxide radicals (O2
-) that
kill bacteria.

130. Importance of Glycerophospholipids
1. They are important constituents of tissues
especially nerves.
2. They are constituents of cell membranes so they
play a role in controlling cell permeability.
3. DPPC is a component of lung surfactant that
reduces the surface tension inside lung alveoli
thereby helping lung inflation.
4. A cephalin is a blood clotting factor.

131. Importance of Glycerophospholipids (cont.)
5. They show hydrotropic properties: i.e. they render
water-insoluble substances more soluble in
aqueous solutions through the formation of
micelles so, they help the transport of fats across
the intestinal mucosa.

132. N.B.
 The amount of phospholipids in the body remains
constant even during starvation, so they are called
the constant element of fat.

133. Arrangement of Glycerophospholipids in
Aqueous Medium
Because phospholipids are amphipathic molecules,
they are arranged in aqueous environment in one of
2 forms:
A. Micelle
B. Bilayer
In both forms, the hydrophobic hydrocarbon tails lie

134. Arrangement of Glycerophospholipids in
Aqueous Medium(cont.)
internally and are hidden from the aqueous medium
while the hydrophilic heads lie externally and are
exposed on the surface.
 Adjacent hydrocarbon tails are attracted to each
other by hydrophobic interactions while the polar
heads form hydrogen bonds with H2O.

135. Arrangement of Glycerophospholipids in
Aqueous Medium

136. B. Sphingophospholipids (sphingomyelin)
CH3 - (CH2)12- CH = CH - CH - CH - CH2 - O - P - O - Choline
NH
C=O
R
OH O
O
+
Amide bond
Acyl group
of fatty acid
Sphingosine

137. Ceramide
Ceramide is composed of sphingosine linked
by an amide bond to the acyl group of a fatty
acid.
CH3 - (CH2)12- CH = CH - CH - CH - CH2 - OH
NH
C=O
R
OH
+
Amide bond
Acyl group
of fatty acid
Sphingosine

138. N.B.
Sphingosine + fatty acid is called ceramide

139. Importance of Sphingophospholipids
1. They are important constituents of tissues
especially the brain and the myelin of nerves.
2. They are constituents of cell membranes.

140. Sphingophospholipids (sphingomyelins) are
amphipathic molecules
 Sphingophospholipids are amphipathic molecules
i.e. each molecule has a hydrophilic (polar) head
(formed of the phosphate group and choline) and a
hydrophobic (non-polar) tail (formed of
sphingosine and the hydrocarbon chains of the
fatty acid).

141. B. Sphingophospholipids (sphingomyelins)
.
CH3 - (CH2)12- CH = CH - CH - CH - CH2 - O - P - O - Choline
NH
C=O
R
OH O
O
+
Acyl group
of fatty acid
Sphingosine
Hydrophilic
Hydrophobic
Phosphoric acid

142. Function of Sphingophospholipids
1. They are important constituent of the brain and
the myelin of nerve fibers.
2. They are important membrane components.

143. 2- Glycosphingolipids (Glycolipids)
Sulphatides
(contain sulphate group)
Acidic
Neutral
(called cerebrosides)
Sulphatides
(contain sulphate group)
Gangliosides
(contain N-acetyl
neuraminic acid
(NANA)

144. Glycosphingolipids
Neutral Acidic
consist of
Sulphatides
Gangliosides
consist of
consist of
Ceramide
(sphingosine +Fatty acid)
One or more
Sugar residue
Ceramide Galactose Ceramide One or more
sugar residue
N-acetyl
neuraminic acid
(NANA)
Sulfate
group

145. Glycosphingolipids
(Glycolipids)
Neutral Glycolipids
Acidic Glycolipids

146. Neutral Glycolipids
consist of
Ceramide
(sphingosine + Fatty acid)
One or more
Sugar residues

147. Acidic Glycolipids
Sulphatides
consist of
Ceramide Galactose
N-acetyl
neuraminic acid
(NANA)
Sulfate
group
Ceramide One or more
sugar residues
consist of
Gangliosides

148. Neutral Glycosphigolipids

149. Sulfatides (Galactocerebroside Sulfate)

150. Gangliosides

151. III. Derived Lipids
 They are either derived from simple and
compound lipids (1,2,3) or associated with lipids
(4,5,6), and they possess the general physical
characteristics of lipids

152. III. Derived Lipids (cont.)
They include:
1. Fatty acids
2. Alcohols
e.g. glycerol, sphingosine.
3. Steroids
4. Carotenoids
5. Fat-soluble vitamins
Vitamins K, E, D and A

153. Steroids
. They contain a steroid nucleus (sterane ring) which
is composed of:
 3 cyclohexane rings
 1 cyclopentane ring
A B
C D

154. 154
Steroids
They contain a steroid nucleus (sterane ring) which
is composed of:
 3 cyclohexane rings
 1 cyclopentane ring

155. Steroids
A B
C D
Steroid nucleus (sterane ring)

156. Steroids
 Steroids include:
1. Sterols
2. Steroid hormones
3. Bile acids and salts
4. Vitamins D

157. Sterols
 This is a group of steroids that contans a hydroxyl
group at C3 (i.e. it is an alcohol), and an aliphatic
side chain at C17.
Types of sterols
1. Animal sterols
e.g. Cholesterol and 7-dehydrocholesterol.
2. Plant sterols
e.g. ergosterol.

158. Cholesterol
 It is the main sterol in the human body.
 It is an alcohol.
 It is often found as cholesterol ester (i.e. in
combination with a fatty acid (usually linoleic aid)
attached to the hydroxyl group at C3.

159. Occurrence of cholesterol in Humans
 All cell membranes
 Liver
 Brain
 Blood
Normal plasma cholesterol: 150 – 250 mg/dl.
1/3 of plasma cholesterol exists as free cholesterol
2/3 plasma cholesterol exists as cholesterol ester.
159

160. N.B.
 Plants do not contain cholesterol. They contain β-
sitosterol.
 β-sitosterol is poorly absorbed by humans. It also
blocks the absorption of dietary cholesterol. So
ingestion of plant steroid esters is used in
reduction of plasma cholesterol in cases of
hypercholesterolemia.

161. Structure of Cholesterol
.
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
A B
C D

162. Structure of Cholesterol
.
HO
21 22
20 23
27
26
25
24
3

163. Free Cholesterol is an Amphipathic Molecule
.
HO
21 22
20
23
27
26
25
24
Hydrophilic
(polar) head
3
Hydrophobic (non-polar) hydrocarbon tail

164. Free Cholesterol is an Amphipathic Molecule
.
Hydrophilic head
Hdyrophobic tail

165. Structure of cholesterol ester
.
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
R- C - OH
O
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
H2O
Cholesterol esterase
Cholesterol
Fatty acid
R- C - O
O
Cholesterol ester

166. Cholesterol Ester is a Hydrophobic Molecule
.
R - C - O
21 22
20
23
27
26
25
24
Hydrophobic (non-polar)
acyl group
3
Hydrophobic (non-polar) hydrocarbon chain
O

167. Sources of Cholesterol
 It is formed in the body from acetyl CoA.
 It is present in diet e.g. egg yolk, meat, liver and
brain. (It occurs in animal fats but not in plant
fats).

168. Biomedical importance of Cholesterol
1. It is the main sterol in human body;
a. It is a component of the nervous tissue, brain,
suprarenal gland, and bile.
b. It is a major constituent of the plasma
membrane.
2. It is the precursor of sex hormones, cortical
hormones, vitamin D and bile acids and salts.

169. Cholesterol (cont.)
3. High blood cholesterol level will lead to;
a. Atherosclerosis
It is due to precipitation of cholesterol in the walls
of blood vessels that will lead to:
 Hypertension
 Coronary artery disease e.g. myocardial infarction
 Cerebrovascular disease e.g. stroke
b. Gall bladder stones

170. 7- dehydrocholesterol
 It is present in the skin and is converted by
ultraviolet (UV) rays of the sunlight into vitamin D3
(cholecalciferol), so it is considered as provitamin
D3.

171. 7- dehydrocholesterol
.
HO
21 22
20 23
27
26
25
24
3

172. Conversion of 7- dehydrocholesterol to
Vitamin D3
.
H3C

173. Plant sterols (e.g. ergosterol)
 It is present in lower plants as yeast and moulds.
 It is converted by ultraviolet rays of the sun into
vitamin D2 (ergocalciferol), so it is considered as
rovitamin D2.

174. Structure of Ergosterol
.
HO
21 22
20 23
27
26
25
24
3

175. Conversion of Ergosterol to Vitamin D2
H3C
Ergosterol
(provitamin D2)
Ergocalciferol
(vitamin D2)

176. Bile Acids
 They are hydroxy derivatives of cholanic acid.
 They are obtained in the liver by oxidation of
cholesterol at C24 with removal of the last 3 carbon
atoms.
 They are the end products of cholesterol
catabolism in the body because the body can not
break down the steroid nucleus.

177. Structure of Cholanic Acid
.
COOH
21 22
20 23
24
3

178. Example of Bile Acids; Cholic Acid
 Cholic acid (3, 7, 12 trihydroxycholanic acid) is
one of the bile acids.
 Cholic acid can be conjugated with either glycine
or taurine to produce glycocholic acid or
taurocholic acid respectivey.

179. Example of Bile Acids; Cholic Acid
(3,7,12 trihydroxycholanic Acid
.
COOH
21 22
20 23
24
3
OH
HO
OH
12
7

180. Structure of Glycoocholic Acid
CO
NH-CH2-COOH
21
22
20
23
24
3
HO
OH
12
7
Glycine
OH

181. Structure of Taurocholic Acid
CO
NH-(CH2)2-SO3H
21
22
20
23
24
3
HO
OH
12
7
Taurine
OH

182. Bile Salts
 They are the products of conjugation of bile acids
with glycine or taurine mainly in their sodium or
potassium salts.
Examples
1. Sodium glycocholate.
2. Sodium taurocholate.

183. Sodium Glycoocholate; a Bile Salt
CO
NH-CH2-COONa
21
22
20
23
24
3
HO
OH
12
7
Glycine
OH

184. Sodium Tauroocholate; a Bile Salt
CO
NH-(CH2)2-SO3Na
21
22
20
23
24
3
HO
OH
12
7
Taurine
OH

185. Functions of Bile Salts
1.They activate pancreatic lipase, so they help the
digestion of lipids.
2.They are strong emulsifying agents so they help
the digestion of dietary lipids by pancreatic
lipase.
3.They have hydrotropic properties i.e. they make
water-insoluble compounds more soluble in
aqueous solution through the formation of
185

186. mixed micelles so:
a. They help the absorption of fats and fat-soluble
vitamins.
b. They keep biliary cholesterol in solution, so
prevent the formation of gallstones.
4. They have choleritic action i.e. they stimulate
liver cells to secrete bile.
186

187. N.B.
The liver converts both primary and secondary
bile acids into bile salts by conjugation with
glycine or taurine, and secretes them into the
bile.
187

188. Metabolism of Lipids

189. Digestion of Lipids

190. Sources of Dietary Lipids
• Oils
• Butter
• Liver
• Brain
• Egg yolk

191. Types of Dietary Lipids
• Triacylglycerol (TAG) 90%
• Phospholipids (PL)
• Cholesterol (C) & cholesterol ester (CE)
• Free fatty acids (FFAs)
• Fat-soluble vitamins (A,D,K,E)
10%

192. 1. Digestion of Triacylglycerols (TAG)
In the mouth:
No digestion of fat occurs
In the stomach
Lingual and gastric lipases
 Lingual lipase is secreted by glands at the back of
the tongue, while gastric lipase is secreted by
the gastric mucosa.
 They are relatively acid-stable lipases, optimum
pH: 4-6.

193.  They are specific for digestion of TAG that contain
short chain FAs such as those of milk.
 They play an important role in lipid digestion
particularly in:
1. Neonates, for whom milk fat is the primary
source of calories.
2. Individuals with pancreatic insufficiency (such
as those with cystic fibrosis) in whom pancreatic
lipase (the main enzyme in fat digestion) is
deficient.

194. In the small intestine
Pancreatic lipase
 It is the main enzyme in TAG digestion.
 It hydrolyzes the ester bonds of TAG at positions 1
and 3 producing 2-monoacylglycerol and 2 FAs.
 Its optimum pH: 7-8.
 It needs prior emulsification of lipids to work. This
is carried out by;
1. Bile salts.
2. Mechanical agitation due to peristalsis.

195. Bile salts are emulsifying agents
 Bile salts emulsify fat by lowering their surface
tension, therefore they change large fat particles
into smaller ones having larger surface area, so
they can be easily digested by enzymes.

196. Bile salts are emulsifying agents
Bile salts
Emulsification
Large lipid particle
(small surface area)
Small lipid particles
(larger surface area)

197.  The enzyme is activated by;
1. Bile salts
2. Colipase
• It is a protein present in pancreatic secretion.
• It is secreted as the zymogen, procolipase, which
is activated in the intestine by trypsin.
• It anchors pancreatic lipase at the lipid-aqueous
interface and causes a conformational change in
the lipase that exposes its active site.

198. Digestion of Triacylglycerols (TAG)
1CH2 O C R1
1CH2 OH
R2 C O 2CH R2 C O 2CH
3CH2 O C R3 2H2O 2RCOOH 3CH2 OH
Triacylglycerol 2- monoacylglycerol
Pancreatic lipase
O
O
O
O
Pancreatic
isomerase
Absorbed
as such
72%
28%

199. Digestion of Triacylglycerols (TAG) (cont.)
1CH2 O C R1
HO 2CH
3CH2 OH
1CH2 OH
HO 2 CH
3CH2 OH
Glycerol
O
1- monoacylglycerol (28%)
22% 6%
Absorbed as such
(i.e. 1- monoacylglycerol)
+ R1-COOH
(FFA)
Pancreatic lipase
(in intestinal lumen)
Intestinal lipase
(at bruch border)
FFA
Glycerol

200. N.B.
- Orlistat is an antiobesity drug that inhibits gastric
and pancreatic lipases fat digestion and
absorption loss of weight.

201. Cystic Fibrosis (CF)
Prevalence
- It is the most common lethal genetic disease in
Caucasians of Northern European ancestry, and
has a prevalence of about 1:3,000 births.
Genetics
- It is an autosomal recessive disorder.
Cause
- It is caused by mutations to the gene for the CF
transmembrane conductance regulator (CFTR)

202. protein that functions as a chloride channel.
Pathogenesis
- Defective CFTR decreased secretion of chloride
and increased reabsorption of sodium and water.
- In the pancreas, the decreased hydration
thickened secretions, so pancreatic enzymes are
unable to reach the intestine pancreatic
insufficiency.
Treatment
- Enzyme replacement therapy.

203. CFTR Protein
.
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-

204. Human chromosomes
46 chromosomes (23 pairs)
44 Somatic chromosomes
(autosomes)
X Y
in males
2 Sex chromosomes
Determine the somatic features of the
individual e.g. length, color of hair,
protein synthesis etc.
Determine the sex of the
individual (male or female)
X X
In females

205. Mode of inheritance of characters by
autosomes
Autosomal dominant Autosomal recessive

206. Mode of inheritance of the color of the hair by
autosomes
- Each character is represented by two genes.
- The character of the black hair is dominant and its
gene is represented by the letter B
- The character of the blonde hair is recessive and
its gene is represented by the letter b
 If the child is BB, his hair will be black.
 If the child is bb, his hair will be blonde.
 If the child is Bb, his hair will be black because
the character of black hair is autosomal
dominant.

207. 2.Digestion of cholesterol & cholesterol ester
• Most dietary cholesterol is present in the free
(nonesterified) form, with 10–15% present as
Cholesterol ester (the esterified form).
• Free cholesterol is not digested and is absorbed
as such.
• Cholesterol ester is digested by cholesterol ester
hydrolase (= cholesterol esterase) into free
chohesterol and free fatty acid (FFA).

208. Digestion of Cholesterol Ester
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
R- C ~
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
R-C- OH
Cholesterol ester
Fatty acid
O
Cholesterol
208
O
H2O
H
Cholesterol ester hydrolase
(esterase)

209. 3. Digestion of Phospholipids
- They are digested by pancreatic phospholipase A2
(PLA2) (acts on ester bond at position 2) into
lysophospho lipids.
- PLA2 is first released as a proenzyme that is
activated by trypsin.
- Lysophospholipids are further digested by
intestinal phospholipase A1 (PLA1) (acts on ester
bond at position 1) into glyceryl phosphoryl base.

210. 3. Digestion of Phospholipids (cont.)
- Glyceryl phosphoryl base (e.g. glyceryl phosphoryl
choline) is excreted, absorbed, or further
degraded by either phospholipase C which
separates phosphoryl base from glycerol or
phospholipase D which separates glycerol
phosphate from the free base.

211. Digestion of Phospholipids
CH2 - O - C - R1
R2 - C - O - CH
CH2 - O - P - O - Base
O
O
O
O
Phospholipase A2
H2O
Phospholipid
R2 - COOH
2
1
3
Bile salts
+

212. Digestion of Phospholipids (cont.)
CH2 - O - C - R1
HO - CH
CH2 - O - P - O - Base
O
O
O
H2O
Lysophospholipid
R1 - COOH
2
1
3
Phospholipase A1

213. Digestion of Phospholipids (cont.)
.
CH2-OH
HO-CH
CH2 – O – P – O – Base
Absorbed
O
O
Excreted
Further
degraded
Glyceryl phosphoryi base

214. Degradation of Glyceryl Phosphoryl Base
.
CH2-OH
HO-CH
CH2 – O – P – O – Base
Glycerol +
Phosphoryl base
Glycerol Phosphate +
base
Phospholipase C Phospholipase D
O
O

215. 3. Digestion of phospholipids by
Phospholipases
.
CH2 - O - C – R1
R2 - C - CH
CH2 - O - P - O - Base
O
O
O
O
1
2
3
Phospholipase A1
Phospholipase A2
Phospholipase D
Phospholipase C

216. N.B.
• Phospholipase A2 (PLA2) is of pancreatic origin,
while phospholipases A1, C, and D (PLA1, PLC,
PLD) are of intestinal origin.
• End products of digestion of phospholipids are
lysophosphatide (mainly), FFA, glycerol phosphate
ad nitrogenous base.

217. Overview of Lipid Digestion
Phospholipid
Phospholipases
A2&A1

218. Hormonal control of lipid digestion
The small intestine secretes 2 peptide hormones:
I. Cholecystokinin (CCK).
2. Secretin.
N.B.
Chyme is the name given to the semifluid mass of
partially digested food that passes from the stomach
to the duodenum.

219. 1. Cholecystokinin (CCK)
It is a peptide hormone produced by mucosal cells
of the lower duodenum & jejunum.
Stimulus for release
The presence of lipids & partially digested proteins
in the intestine.

220. 1. Cholecystokinin (CCK) (cont.)
Action
1. On gall bladder → contraction & release of bile.
2. On exocrine pancreas → release of pancreatic
enzymes
3. On stomach → gastric motility.

221. 2. Secretin
It is a peptide hormone produced by mucosal cells of
the small intestine.
Stimulus for release
Low pH of chyme entering the intestine.

222. 2. Secretin (cont.)
Action
It stimulates the pancreas & the liver to release a
watery solution rich in bicarbonate to neutralize the
acidic pH of the chyme entering the intestine and
make its pH suitable for the action of the digestive
enzymes in the intestine.

223. Hormonal Control of Lipid Digestion

224. Steatorrhea
Definition
It means excessive loss of lipids in stools.
Causes
1. Defect in the secretion of bile due to liver or gall
bladder disease .
2. Defect in the secretion of pancreatic enzymes
due to pancreatic disease.
3. Disease of the mucosal cells of the small
intestine defect in the absorption of lipids.

225. Steatorrhea (cont.)
Effects
Deficiency of fat-soluble vitamins and essential
fatty acids due to their loss in stool.

226. Steatorrhea

227. Absorption of lipids
• Glycerol and short and medium chain FFAs in the
intestinal lumen pass by diffusion to inside the
intestinal cells and then to the portal blood (where
FFAs are carried by plasma albumin) and finally to
the liver.
• Long chain FFAs + 2- monoacylglycerol + free
cholesterol + bile salts + fat-soluble vitamins form
mixed micelles in which the hydrophilic regions are

228. Absorption of lipids (cont.)
directed outwards facing the aqueous environment
of the intestinal lumen and the hydrophobic
regions are located in the center of the micelle.
• These micelles pass from the intestinal lumen to
inside the intestinal mucosal cells where TAG,
cholesterol ester and phospholipids are re-
synthesized as follows:

229. Absorption of Lipids
. Intestinal lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Fat-soluble vitamins
Bile
salts
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
lymphatics
Thoracic
duct
Systemic
circulation
Left
subclavian
vein
Chylomicron
Mixed
micelle
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
Mucosal
Cell
Digestion
(stomach &
Intestine)
Form
Resynthesize
Portal
vein
Liver
Apoproteins
Mixed
micelle
Bile
salts
(FFAs are
carried by
plasma
albumin)
Long chain FAs
2-monoacylglycerol
Free cholesterol
Fat-soluble vitamins
Short & medium
chain FAs
Glycerol
Short & medium
chain FAs
Glycerol
Exocytosis
Milky
appearance
of plasma

230. N.B.
 FAs are poorly soluble in aqueous solution, thus,
they travel in blood bound to plasma albumin.
.

231. Amphipathic Lipids
. Aqueous environment
Aqueous environment
Hydrophilic heads
Hydrophobic tails

232. Arrangement of amphipathic lipids in a
micelle
. Hydrophilic
outer surface
Hydrophobic
interior
Aqueous external environment
Aqueous external environment

233. Structure of Mixed Micelles
Glycerylphosphoryl
base

234. • Long chain fatty acids are activated by thiokinase
enzyme (acyl COA synthetase) forming acyl COA.
• Acyl CoA esterifies 2- monoacylglycerol at 1 and 3
posisions producing TAG.
• TAG are also formed inside the intestinal cells
from acyl-COA and active glycerol (-glycerol
phosphate) which is derived from dihydroxy
acetone phosphate of glycolysis.

235. Activation of Fatty Acids
Fatty acid + CoASH AcylCoA
ATP AMP + PPi
Acyl CoA synthetase
(Thiokinase)
Mg 2+
(Active FA)

236. Re-synthesis of Triacylglycerols (TAG)
1CH2 OH 1CH2 O C R1
R2 C O 2CH R2 C O 2CH
3CH2 OH 2 R C~SCoA 2 CoASH 3CH2 O C R3
2(β)- monoacylglycerol Triacylglycerol
Transacylase
O
O
O
O
O
Acyl CoA
(Active FA)

237. Re-synthesis of Cholesterol Ester
.
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
R- C ~SCoA
O
O
H
CH3
CH3
CH3
CH3
C
H3
1
3
2
4
5
10
9
8
11
12
13
14 15
16
17
20
23
24
25
26
27
6
7
21 22
18
19
CoASH
Cholesterol esterase
Cholesterol
Fatty acid
R- C - O
O
Cholesterol ester
237

238. Re-synthesis of Phospholipids
CH2 - O - C - R1
HO - CH
CH2 - O - P - O - Base
CH2 - O - C - R1
R2 - C - O - CH
CH2 - O - P - O - Base
O
O
CoASH
Lysophospholipid
2
1
3
O
1
2
3
O
O
R- C ~SCoA
O
O
O
Phospholipid

239. Secretion of Lipids from the Intestinal
Mucosal Cells
• TAG + free cholesterol + cholesterol ester +
phospholipids + proteins called apoproteins (apo)
e.g. Apo B-48, Apo-CII, and Apo-E form a water-
soluble lipoprotein complex called chylomicrons.
• Amphipathic lipids (free cholesterol and phospho-
lipids) form the outer part of chylomicrons, while
hydrophobic lipids (TAG + cholesterol ester) are
present in the interior of the particle.

240. Chylomicron
Free cholesterol
E

241. • TAG represents about 90% of the content of
chylomicron particle.
• Chylomicrons are released by exocytosis from the
intestinal mucosal cells into the intestinal
lymphatics thoracic duct left subclavian
vein systemic circulation.

242. Use of Dietary Lipids
(Metabolism of Chylomicrons)
• TAG in chylomicron is broken down by plasma
lipoprotein lipase (LPL) into FFA & glycerol.
• LPL is activated by apo-CII and phospholipids of
the chylomicron particle.
• The remaining part of chylomicron is called
chylomicron remnant.

243. Metabolism of Chylomicrons
Apo E receptor
PL
PL

244. Plasma Lipoprotein Lipase (LPL)
(Plasma Clearing Factor)
• This enzyme is synthesized primarily by adipocytes
and muscle cells.
• It is secreted and becomes associated with the
luminal surface of endothelial cells of the capillary
beds of the peripheral tissues e.g. adipose tissue,
skeletal muscles, heart, lung, kidney and liver.
• It is activated by apo-CII and phospholipids of the
chylomicron and VLDL particles as well as by
heparin.

245. Plasma Lipoprotein Lipase (LPL)
• Deficiency of lipoprotein lipase or its coenzyme
Apo C11 accumulation of chylomicrons and
TAGs in blood (a rare autosomal recessive disorder
called type 1 hyperlipoproteinemia.

246. Plasma Lipoprotein Lipase (LPL)
.
LPL
Blood
Blood capillary
FFA Glycerol
Chylomicron remnant
Chylomicron
Cells of
peripheral
tissues
Liver cells
only
TAG
Endothelial cells
C,CE,Pl
C,CE,Pl
TAG
Apo
CII
+

247. Type 1 Hyperlipoproteinemia
.
LPL
Blood
Blood capillary
FFA Glycerol
Chylomicron remnant
Chylomicron
Cells of
peripheral
tissues
Liver cells
only
TAG
Endothelial cells
C,CE,Pl
C,CE,Pl
TAG
Apo
CII

248. Catabolism of TAG of Chylomicrons by
Plasma LPL
1CH2 O C R1
1CH2 OH
R2 C O 2CH HO 2CH
3CH2 O C R3 3 H2O 3 R - C - OH 3CH2 OH
Triacylglycerol Glycerol
Lipoprotein Lipase (LPL)
O
O
O
O
O
O
O
Fatty Acid

249. Fate of glycerol
Glycerol
Passes exclusively to Liver
Glycerol 3-phosphate
(Active glycerol)
Glycolysis Gluconeogenesis
Energy Glucose
Activation

250. Fate of free fatty acids
• FFA may enter adjacent muscle cells & adipose
tissue cells or transported in the blood, in
association with serum albumin until they are
taken up by most tissue cells and oxidized to
produce energy.
• Adipose tissue cells can also reesterify FFA →
TAG which are stored until needed by tissues.

251. Fate of free fatty acids
Enter Pass to
Enter
Adjacent myocytes Systemic Circulation
bound to plasma albumin
Adjacent
adipocytes
oxidized to
produce energy
oxidized to
produce energy
Most tissues
Re-esterified
Into
TAG
oxidized to
produce
energy
Enter

252. Fate of free fatty acids
Systemic Circulation
bound to plasma albumin
Adjacent
adipocytes
Oxidized to
produce energy
Most tissues
Enter
Re-esterified
into TAG and stored
(in fed state)
Enter Pass to

253. Chylomicron Remnants
• After most TAG has been removed, the remaining
part of chylomicron is called chylomicron remnant.
• Chylomicron remnant contains cholesterol ester,
phospholipids, fat-soluble vitamins, apolipo-
proteins (e.g. Apo B-48, Apo E) and also some
triacylglycerols.
• Chylomicron remnants bind to receptors on the
liver cells and are endocytosed to be hydrolyzed
to their components.

254. • Cholesterol and the nitrogenous bases of PL can
be recycled by the body.
• If removal of chylomicron remnants is defective,
they accumulate in plasma → familial type III
hyperlipoproteinemia.

255. Catabolism of Triacylglycerols
(Lipolysis)

256. Function of Adipose Tissue
 Adipose cells are specialized for:
1. Synthesis and storage of TAG in their cytoplasm
(in fed state).
2. Catabolism of TAG into fatty acids and glycerol
that are transported by blood to other tissues to
be used as a source of energy or as a source of
blood glucose (in the fasting state).

257. Catabolism of Triacylglycerols
(Lipolysis)
 Conditions that promote (enhance or stimulate)
lipolysis:
1. Prolonged fasting, starvation and dieting.
2. Severe muscle exercise.
3. Uncontrolled diabetes mellitus.

258. Lipolysis (cont.)
Lipolysis is carried out by 3 tissue lipases;
1. Hormone-sensitive lipase (HSL).
2. Diacylglycerol lipase.
3. Monoacylglycerol lipase.
N.B.
Lipolysis is inhibited in case of high plasma level of
insulin & glucose because HSL is dephosphorylated
(inactive).

259. Steps of Lipolysis
1CH2 O C R1
1CH2 OH
R2 C O 2CH R2 C O 2CH
3CH2 O C R3 H2O R1COOH 3CH2 O – C- R3
Triacylglycerol 2,3- diacylglycerol
Hormone-sensitive lipase
(HSL)
O
O
O
O
Diacylglycerol
lipase
O
H2O
R3COOH

260. Steps of Lipolysis (cont.)
1CH2 OH 1CH2 OH
HO 2 CH R2 C O 2CH
3CH2 OH R2COOH H2O 3CH2 OH
Glycerol 2- monoacylglycerol
Monoacylglycerol lipase
O

261. Fate of Glycerol
• Glycerol released from lipolysis in adipose tissue
can not be metabolized due to low activity of
glycerol kinase , so it is transported to blood then
to the liver and other tissues which contain active
glycerol kinase.

262. Fate of Glycerol (cont.)
Glycerol in Liver
Active glycerol Kinase
Glycerol 3- phosphate
Brain, RBCs and other tissues
Gluconogenesis
Glucose
Pass to
Blood
Then pass to
production of energy
Undergoes oxidation

263. Fate of Free Fatty Acids (FFAs)
• They leave adipocytes and are released into blood
where they are bound to plasma albumin and are
taken by tissues such as kidney and cardiac and
skeletal muscles for oxidation to produce energy.

264. N.B.
 FA oxidation does not occur in RBCs (due to
absence of mitochondria ) and brain (because of
the impermeable blood-brain barrier).
.

265. N.B.
 TAG stores in adipose tissue are continually
undergoing lipolysis and re-esterification. The
result of these two processes determine the
magnitude of FFAs pool in adipose tissue which in
turn is the source and determinant of the level of
FFAs in the plasma.
.

266. N.B.
 When the rate of re-esterification does not match
the rate of lipolysis, FFAs accumulate and diffuse
into the plasma where they bind to albumin and
raise the concentration of plasma free fatty acids.
.

267. Regulation of Lipolysis
.
Glucagon (during fasting)
Epinephrine, norepinephrine & ACTH (during stress)
Inactive
Adenylate cyclase
Active
Adenylate cyclase
+
+
ATP cAMP
Inactive
Protein kinase
Active
Protein kinase
+
ATP ADP
Inactive
Hormone-sensitive
lipase
Active
Hormone-sensitive
lipase
H2O
Pi
Insulin
+
P
+
5ˋ AMP
Phosphodiesterase
+
Phosphatase
Insulin

268. Fatty Acid Pools in Adipose Tissue
Fatty acids pool 1
 It is formed by lipolysis of TG in the adipose
tissue.
 It supplies fatty acids for:
1. Re-esterification within the adipose tissue.
2. The plasma.

269. Fatty Acid Pools in Adipose Tissue (cont.)
Fatty acids pool 2
 It results from the action of lipoprotein lipase on
TAG of chylomicrons inside the adipose tissue.
 It is reconverted to acyl CoA and re-esterified to
TAG within the adipose tissue or oxidized giving
rise to energy within this tissue.

270. Oxidation of Fatty Acids

271. Types of fatty acid oxidation
ω  
CH3 – CH2 - CH2 - CH2 - CH2 - COOH
- oxidation
(Minor pathway)
 - oxidation
(Major pathway)
ω – oxidation
(Minor pathway)

272. - Oxidation of fatty acids
 - oxidation of
even number
fatty acids
 - oxidation of
odd number
fatty acids

273. Source of Fatty acids used in  - Oxidation
 Blood Fatty acids that are used in are  - Oxidation
are derived from:
a. TAG of blood lipoproteins (chylomicrons and
VLDL). or
b. TAG of adipose stores.
• These fatty acids travel complexed with albumin in
the blood to be taken by tissues (e.g. heart,
skeletal muscle & kidney) where they are oxidized.

274.  - Oxidation of Even Number Fatty Acids
Definition
 Oxidation of the fatty acid at the  carbon with
successive removal of 2 carbon atoms from the
carboxyl terminal end in the form of acetyl CoA.

275.  - Oxidation of Even Number Fatty Acids
(cont.)
Site
 Mitochondrial matrix of most tissues especially
liver, kidney cortex, and cardiac and skeletal
muscles.
 It does not occur in RBCs (due to absence of
mitochondria ) and brain (because of the
impermeable blood-brain barrier).

276. β-Oxidation of fatty acids
.
Short and medium
chain FAs
Short and medium
chain acyl CoA
Activation
Long chain acyl CoA
Long chain acyl CoA
β-oxidation
Carnitine shuttle
Long chain FA
Short and medium
chain FAs
Mitochondrion
Cytosol
Matrix
Activation Acyl CoA synthetase
Acyl CoA synthetase

277. 1. Activation of Fatty Acid to acyl CoA
R - C - OH + HS~CoA R - C~ S - CoA
Fatty acid ATP AMP + P~P Acyl CoA
( Active FA)
Acyl-CoA synthetase
Mg2+
O O

278. High-energy
phosphate bonds
Low-energy
phosphate bond
High Energy Phosphate Bonds of ATP
.
α
β
γ
Adenosine triphosphate (ATP)
Adenine
Adenosine
Ribose

279. N.B.
- CoASH = Coenzyme A or CoA (-SH is the active
group in this compound).
- AcylCoA synthetase is also called thiokinase.
- Activation of one fatty acid breaks down one
molecule of ATP to AMP (not ADP). This is virtually
equivalent to the consumption of 2 ATPs molecules
(each is broken down to ADP).
- P~P is called pyrophosphate.

280. Transport of Fatty Acids from Cytosol to
Mitochondrial Matrix for β-oxidation
 Long chain FAs are firstly activated to long chain
acyl CoA in the cytosol before they are
transported to the mitochondrial matrix where β-
oxidation occurs.
 Long chain acyl CoA is a bulky molecule, so it
can not traverse the inner mitochondrial
membrane, so it is transported to the matrix of the
mitochondria via a special transport mechanism

281. Transport of Fatty Acids from Cytosol to
Mitochondrial Matrix for β-oxidation (cont.)
 Short and medium-chain FAs can pass freely
though the inner mitochondrial membrane to
mitochondrial matrix and are not in need for
carnitine shuttle. Once inside, they are activated
by enzymes of the mitochondrial matrix.

282. Transport of Fatty Acids from Cytosol to
Mitochondrial Matrix for β-oxidation
.
Short and medium
chain FAs
Short and medium
chain acyl CoA
Activation
Long chain acyl CoA
Long chain acyl CoA
β-oxidation
Carnitine shuttle
Long chain FA
Short and medium
chain FAs
Outer membrane
of mitochondrion
Cytosol
Matrix
Activation Acyl CoA synthetase
Acyl CoA synthetase
Inner membrane
of mitochondrion
Cell

283. 2. Transport of long chain acyl CoA from the cytosol
to the mitochondrial matrix
• Long chain acyl CoA is a bulky molecule to which
the inner mitochondrial membrane is impermeable
so, it needs carnitine system (carnitine shuttle) to
be transported across the inner mitochondrial
membrane.
N.B.
• Short and medium chain FAs cross the inner
mitochondrial membrane without the need for
carnitine system. Once inside the mitochondria,
they are activated by enzymes of the
mitochondrial matrix.

284. Carnitine Shuttle
Components
It is composed of carnitine and 3 enzymes:
1. Carnitine acyl transferase I (CAT-I): located in the
outer mitochondrial membrane.
2. Translocase: located in the inner mitochondrial
membrane.
3. Carnitine acyl transferase II (CAT-II): located on the
inner surface of the inner mitochondrial membrane.

285. Carnitine Shuttle (cont.)
Structure of carnitine
It is -hydroxy--trimethyl-ammonium butyrate.
Sources of carnitine
1. Diet primarily meat products.
2. Carnitine is synthesized in liver and kidney (but
not in skeletal or heart muscle) from the amino
acids lysine and methionine.
α
γ β
(CH3)3-N+-CH2-CH(OH)-CH2-COOH

286. Carnitine Shuttle (cont.)
Function of carnitine shuttle
It transports long chain acyl CoA molecules across
the inner mitochondrial membrane.

287. Carnitine Shuttle
Acyl CoA synthetase
Carnitine acyl
transferase I
(CAT-I)
Carintine acyl
transferase II
(CAT-II) Acylcarnitine
Translocase
Acyl CoA
Long chain fatty acid
Cytosol
Mitochond-
rial matrix
Inter-
membrane
space

288. Carnitine Shuttle (cont.)
Inhibition
Malonyl CoA inhibits carnitine acyl transferase I
prevention of the entry of long chain acyl CoA into
the mitochondrial matrix inhibition of -
oxidation of long chain FAs.

289. Carnitine Deficiency
Causes
Primary deficiency due to:
1. Congenital deficiencies in one of the components
of the carnitine palmitoyltransferase system.
2. Defect in renal tubular reabsorption of carnitine.
3. Defect in carnitine uptake by cells.

290. Carnitine Deficiency (cont.)
Secondary deficiency due to:
1. Liver disease causing decreased synthesis of
carnitine.
2. Malnutrition or strictly vegetarian diets.
3. Increased requirement for carnitine e.g. due to
pregnancy, severe infections, burns, or trauma.
4. Hemodialysis, which removes carnitine from the
blood.

291. Carnitine Deficiency (cont.)
Manifestations
Genetic CPT-I (CAT-I) deficiency
It affects the liver resulting in severe hypoglycemia,
coma, and death.
CPT-II (CAT-II) deficiency
It occurs primarily in cardiac and skeletal muscle
resulting in cardiomyopathy and muscle weakness
with myoglobinemia following prolonged exercise.

292. Carnitine Deficiency (cont.)
Treatment
1. Avoidance of prolonged fasts.
2. Intake of a diet high in carbohydrate and low in
long chain fatty acids.
3. Supplementation with medium-chain fatty acids.
4. Supplementation with carnitine in cases of
carnitine deficiency.

293. Reactions of - oxidation
  - oxidation occurs in repeated cycles.
 Each cycle consists of 4 steps;
1. Oxidation
2. Hydration
3. Oxidation
4. Thiolytic cleavage

294. Reactions of - oxidation
O
CH3- (CH2)n - CH2 - CH2 - C ~SCoA
Acyl CoA
Acyl CoA dehydrogenase
FADH2
O
CH3- (CH2)n - CH = CH - C ~SCoA
2,3-Enoyl CoA (α,β-unsaturated acyl CoA)
Enoyl CoA hydratase
ETC
1
3 2
1
2
3
H2O
FAD
2 ATP
α


295. CH3- (CH2)n - CH - CH2 - C ~SCoA
3-hydroxy acyl CoA
CH3- (CH2)n - C - CH2 - C ~SCoA
3-ketoacyl CoA
CH3- (CH2)n- C ~ SCoA
Acyl CoA (shorter by 2 carbons)
ETC
1
2
3
3 2 1
NAD+
NADH+H + 3 ATP
Thiolase
OH O
O
O
3-hydroxyacyl CoA
dehydrogenase
CoASH
O
O
1
2
3
Repeats the cycle again
at the first step
Enters CAC
CH3 - C ~SCoA
Acetyl CoA

296. N.B.
There are 4 types of acyl CoA dehydrogenases in
the mitochondria: one for each of the short, medium,
long and very long chain fatty acids.

297. Energy yield from one cycle of - oxidation
 Each cycle of - oxidation produces one mole of
FADH2 (at acyl CoA dehydrogenase step) and one
mole of NADH+H+ (at -hydroxy acyl CoA
dehydrogenase step).
 Oxidation of one mole of FADH2 in respiratory
chain (electron transport chain) produces 2 ATPs.
 Oxidation of one mole of NADH+H+ in respiratory
chain produces 3 ATPs.
 Total energy yield of one cycle of  - oxidation
= 2 + 3 = 5 ATPs.

298. Energy Yield from one Cycle of - oxidation
Acyl CoA
(e.g. 16 carbons)
ETC
FAD + NAD+
FADH2 + NADH+H+
5 ATP
Acyl CoA
(14 carbons i.e.
shorter by 2 carbons)
Acetyl CoA
Citric acid cycle
Repeats the cycle
( e.g. 6 times)
CoA

299. Energy yield from - oxidation of palmitoyl
CoA
• Palmitoyl CoA consists of 16 carbon atoms.
• It generates 8 molecules of acetyl CoA through 7
cycles of - oxidation.
• One cycle of - oxidation generates 5 ATPs.
• So, palmitoyl CoA generates 5X7= 35 ATPs upon
- oxidation.

300. Energetics of - oxidation of palmitoyl CoA
No of cycles Palmitoyl CoA (16 C)
1 acetyl CoA (2C)
14 C
2 acetyl CoA (2C)
12 C
3 acetyl CoA (2C)
10 C
4 acetyl CoA (2C)
8 C
5 acetyl CoA (2C)
6 C
6 acetyl CoA (2C)
4 C
7 acetyl CoA (2C)
acetyl CoA (2C)

301. Energy yield from complete oxidation of
palmitoyl CoA
Palmitoyl CoA consists of 16 carbon atoms.
no of carbons 16
Number of  - oxidation cycles = 1 = 1
2 2
= 8 1 = 7 cycles
7 Cycles of  - oxidation produce 7X5 = 35 ATP.
no of carbons 16
Number of acetyl CoA mol. = = = 8 mol.
2 2
Citric acid cycles produces 8X12 = 96 ATP.
Total energy yield = 35 + 96 = 131 ATP.

302. N.B.
 Complete oxidation of palmitic acid produces 129
ATPs because 2 ATPs are utilized in its activation.
 Oxidation of unsaturated FAs provides less
energy than that of saturated FAs because
unsaturated FAs are less highly reduced
and, therefore, fewer reducing equivalents (FADH2
and NADH+H+) are produced.

303. Regulation of - oxidation of fatty acids
1. β- oxidation and FA synthesis are 2 opposed
pathways and therefore they are reciprocally
regulated, so:
a. malonyl CoA, the first intermediate in FA
synthesis carnitine acyltransferase I
transfer of acyl CoA from cytosol to
mitochondrial matrix β - oxidation.
b. dietary carbohydrate malonyl CoA
carnitine acyltransferase I β- oxidation.

304. Regulation of - oxidation of fatty acids (cont.)
2. NADH/NAD ratio β- hydroxyacyl CoA
dehydrogenase β -oxidation.
3. acetyl CoA thiolase β –oxidation.
4. ATP level in the cell -oxidation (feed back
inhibition).
5. The amount of free fatty acids (FFAs) in the blood,
thus:

305. Regulation of - oxidation of fatty acids (cont.)
a. Fasting and starvation glucagon level
lipolysis FFAs in blood β –oxidation.
b. Stress epinephrine and norepinephrine
lipolysis FFAs in blood β –oxidation.
+
+

306. Medium Chain Acyl CoA Dehydrogenase
(MCAD) Deficiency
Characteristics
1. It is an autosomal recessive disorder.
2. It one of the most common inborn errors of
metabolism, and the most common inborn error of
fatty acid oxidation.
3. It causes severe decrease in FA oxidation &
severe hypoglycemia (because tissues depend on
oxidation of glucose rather than FA oxidation to
obtain their energy needs).

307. 4. Infants are particularly affected by MCAD
deficiency, because their main food is milk, which
contains primarily medium-chain fatty acids.
Treatment
Administration of carbohydrate-rich diet.

308.  - Oxidation of Fatty Acids with an Odd
Number of Carbons
 Odd chain fatty acids are oxidized by the same
sequence of reactions as even chain fatty acids.
However, the product of final thiolytic cleavage is
propionyl CoA and acetyl CoA.
 Acetyl CoA is oxidized in the CAC and propionyl
CoA is converted to succinyl CoA that is also
oxidized in the CAC.

309. - Oxidation of odd number fatty acids
. Odd number fatty acid
(e.g. 15 C)
6 moles of
acetyl CoA
1 mole of propionyl CoA
Oxidized in CAC
D-Methylmalonyl CoA
Succinyl CoA
Oxidized in CAC
Propionyl CoA carboxylase
Methylmolonyl CoA racemase
CO2 + ATP + Biotin
B12
6 cycles of  - oxidation
L-Methylmalonyl CoA
Methylmolonyl CoA mutase

310. Metabolism of Propionyl CoA
H
H
H

311. -oxidation in Peroxisomes
• Very long chain fatty acids (contain 20 or more
carbons) undergo a preliminary -oxidation in
peroxisomes.
• The shortened fatty acid is then transferred to the
mitochondrion for further oxidation.
• The initial dehydrogenation reaction is
catalyzed by FAD- containing acyl CoA oxidase.

312. -oxidation in Peroxisomes
Acyl CoA oxidase
Very long acyl CoA
FAD
FADH2
H2O2
O2
Catalase
H2O + ½ O2

313. α-oxidation of Fatty Acids
Characteristics
1. It is a minor pathway of fatty acids oxidation.
2. It occurs in the endoplasmic reticulum and
mitochondria.
3. It removes one carbon at a time from the carboxyl
end of the fatty acid molecule.
4. It needs an α-hydroxylase that requires NADPH +
H+, molecular oxygen, and cytochrome P450.

314. α-oxidation of Fatty Acids (cont.)
5. It does not need CoASH.
6. It does not aim for the production of energy.
Aim
a. it is concerned primarily with the synthesis of
hydroxyl fatty acid that are required for formation
of brain cerebrosides.
b. It is also needed for oxidation of dietary fatty
acids that are methylated at the β-carbon e.g.

315. α-oxidation of Fatty Acids (cont.)
phytanic acid which is a significant constituent of
milk lipids and animal fat. In this case, β-
oxidation is blocked by the presence of the methyl
group at the β-carbon. So, -oxidation proceeds
first followed by β –oxidation.

316. α-oxidation of Fatty Acids
. CH3 - (CH2) n - CH2 - CH2 - COOH
β α
Fatty Acid
NADPH+H+ + O2
Synthesis of brain
cerebrosides
Aldehyde dehydrogenase
Cyt P450
NADP+ + H2O
α- Hydroxylase
α-Hydroxy Fatty Acid
OH
CH3 - (CH2) n - CH2 - CH - COOH
α
NAD+
NADH + H+

317. Aldehyde dehydrogenase
CO2
Decarboxylase
Fatty Acid
(shorter by one carbon)
α-keto Acid
O
CH3 - (CH2) n - CH2 - C - COOH
α
O
CH3 - (CH2) n - CH2 - C - H
Aldehyde
CH3 - (CH2) n - CH2 - COOH
NAD+
NADH + H+

318. Refsum΄s disease
Cause
Genetic disease due to deficiency of the enzyme α-
hydroxylase.
Mechanism
 The infant is unable to carry out -oxidation of
phytanic acid of milk lipids because its  carbon is
methylated.
 He is also unable to carry out α- oxidation due to

319. Phytanic acid
β
α

320. α-oxidation of Phytanic Acid
.
Phytanic Acid
NADPH+H+ + O2
Aldehyde dehydrogenase
Cyt P450
NADP+ + H2O
α- Hydroxylase
α-Hydroxy Fatty Acid
NAD+
NADH + H+
CH3
CH3 - (CH2) n - CH2 - CH - CH2 - COOH
β α
CH3 OH
CH3 - (CH2) n - CH2 - CH- CH - COOH
α
β

321. Aldehyde dehydrogenase
CO2
Decarboxylase
α-keto Acid
Aldehyde
NAD+
NADH + H+
CH3 O
CH3 - (CH2) n - CH2 - CH - CH - COOH
β - oxidation
α
CH3
CH3 - (CH2) n – CH2 - CH - COOH
α
β
CH3 O
CH3 - (CH2) n - CH2 - CH - C - H
α

322. Refsum΄s disease (cont.)
deficiency of α- hydroxylase accumulation of
phytanic acid in blood , brain and nerves.
Manifestations
1. Deafness.
2. Blindness.
3. Neuropathy.

323. ω-oxidation of Fatty Acids
Characters
1. It is a minor pathway of fatty acids oxidation.
2. It occurs in the endoplasmic reticulum of many
tissues.
3. It is primarily concerned with the oxidation of
medium chain fatty acids of adipose tissue which
are mobilized to the liver under conditions of
ketosis, where the tissue's metabolic state

324. ω-oxidation of Fatty Acids (cont.)
requires a rapid production of energy.
4. It starts with a hydroxylation reaction on the
methyl carbon (omega carbon) that requires a
hydroxylase, NADPH + H+, molecular oxygen, and
cytochrome P450.
5. After hydroxylation, oxidation of the omga carbon
to COOH group produces a dicarboxylic acid.
This is followed by -oxidation at both ends of the
molecule giving rise to succinyl di CoA.

325. ω-oxidation of Fatty Acids
.
CH3 – CH2 – CH2 – (CH2) n – CH2 – CH2 - COOH
β α
ω
Fatty Acid
Hydroxylase
NADPH+H+ + O2
OH - CH2 – CH2 – CH2 – (CH2) n – CH2 – CH2 - COOH
CHO – CH2 – CH2 – (CH2) n – CH2 – CH2 - COOH
Alcohol dehydrogenase
Aldehyde dehydrogenase
Cyt P450
NADP+ + H2O

326. HOOC - CH2 - CH2 - (CH2)n - CH2 - CH2 - COOH
Dicarboxylic Acid
Acyl CoA synthetase
Activation
at both ends
Acyl diCoA
Repeated cycles of
β - oxidation at both ends
β - oxidation β - oxidation
Succinyl diCoA
O
α
β
β
α
CoAS ~ C - CH2 - CH2 - (CH2) n - CH2 - CH2 - C ~ SCoA
O
O
CoAS ~ C - CH2 - CH2 - C ~ SCoA
O

327. Ketone Bodies Metabolism

328. Ketone bodies
They are:
 Acetoacetic acid CH3-CO-CH2-COOH
 3()-hydroxybutyric acid CH3-CH-CH2-COOH
 Acetone CH3-CO-CH3
2 1
OH
3(β)

329. Ketone Bodies Metabolism
Synthesis of ketone
bodies (ketogenesis)
Oxidation of ketone
bodies (ketolysis)

330. Ketogensesis
Definition
It means synthesis of ketone bodies.
Site
Mitochondrial matrix of liver cells.

331. Steps of Ketogensesis
HOOC - CH2 - C - CH2 - C ~ SCoA
H3C - C ~ SCoA
3-hydroxy-3-methyl glutaryl CoA (HMG CoA)
OH
CH3
H2O
CoASH
O
CH3 - C - CH2 - C ~ SCoA
Acetoacetyl CoA
O O
Acetyl CoA
CH3 - C ~ SCoA
O
Acetyl CoA
Acetyl CoA
CoASH
Thiolase
CH3 - C ~ SCoA
O O
HMG CoA synthase
Fatty acid
Acyl CoA
NAD+
CoASH

332. Steps of Ketogensesis
HOOC - CH2 - C - CH2 - C ~ SCoA
H3C - C ~ SCoA
3-hydroxy-3-methyl glutaryl CoA (HMG CoA)
OH
CH3
H2O
CoASH
O
CH3 - C - CH2 - C ~ SCoA
Acetoacetyl CoA
O O
Acetyl CoA
CH3 - C ~ SCoA
O
Acetyl CoA
Acetyl CoA
CoASH
Thiolase
CH3 - C ~ SCoA
O O
HMG CoA synthase

333. .
Acetoacetate
NADH+H+
CH3 - C ~ SCoA
O
HMG CoA lyase
β(3)-hydroxybutyrate
CH3 - C - CH2 - COOH
O
O
Acetyl CoA
CH3 - CH - CH2 - COOH
OH
CH3 - C - CH3
Acetone
NAD+
CO2
Non-enzymatic (spontaneous)
decarboxylation in blood
β(3)-hydroxybutyrate
dehydrogenase

334. N.B.
- HMG CoA synthase is the rate-limiting enzyme in
the synthesis of ketone bodies, and is present in
significant quantities only in the liver.
- Acetoacetate is spontaneously decarboxylated in
the blood to form acetone.
- The generation of free CoA during ketogenesis
allows fatty acid oxidation to continue.

335. - Because NAD+/NADH ratio is low during fatty acid
oxidation, synthesis of -hydroxybutyrate is
favored.

336. Properties of Ketone Bodies
1. They are water soluble substances.
2. They are synthesized at a relatively low rate in
well nourished individuals.
3. Plasma level of ketone bodies < 1 mg/dl (<0.2 mM).
4. Urinary level of ketone bodies < 3 mg/24 hour
urine.

337. Properties of ketone bodies (cont.)
5. Acetone is synthesized in smaller amounts than
other ketone bodies. It is a non-metabolizes side
product. It is a volatile substance that is excreted
by the lungs in the expired air and can not be
detected in the blood.
6. Acetoacetate and -hydroxybutyrate are relatively
strong acids.

338. Properties of ketone bodies (cont.)
7. They are important sources of energy for the
peripheral tissues.

339. N.B.
 The synthesis of HMGCoA also occurs in the
cytosol of the liver cells as well as in all tissues.
 However, HMG COA lyase is absent in the cytosol
and HMG COA is used for cholesterol synthesis.
 The hepatic intramitochondrial HMG COA synthase
thus provides an enzymoligical basis for ketone
body production in the liver.

340. Regulation of Ketogensesis
 HMG CoA synthase is the rate-limiting enzyme in
the synthesis of ketone bodies and it is regulated
as follows:
a. High Plasma FFAs induce HMGCoA synthase.
b. High CoASH level inhibits HMGCoA synthase
and vice versa.

341. Ketolysis
Definition
It is the utilization (oxidation) of ketone bodies.
Site
- Mitochondrial matrix of extrahepatic tissues
especially kidney cortex, cardiac and skeletal
muscles which normally use ketone bodies as a
source of energy in preference to glucose.

342. - The brain can utilize ketone bodies as a source of
energy only during prolonged starvation and they
provide about 75 % of its energy needs under this
condition.
- Ketolysis does not occur in:
a. RBC: due to absence of mitochondria.
b. Liver: due to absence of thiophorase enzyme
that is required for the activation of ketone
bodies.

343. Steps of Ketolysis
.
CH3 – CH – CH2 - COOH
OH
(3) - hydroxybutyrate
CH3 – C – CH2 - COOH
O
Acetoacetate
NAD+
NADH+H+ 3ATPs
ETC
 - hydroxybutyrate
dehydrogenase
β(3)

344. Steps of Ketolysis (cont.)
Succinyl CoA:acetoacetate CoA transferase
(thiophorase)
H
H
H
H

345. Energetics of Ketolysis
 Oxidation of one mole of 3-hydroxbutyrate
27 ATPs.
 Oxidation of one mole of acetoacetateate
24 ATPs.

346. Relation between ketogenesis and ketolysis

347. Ketoacidosis (Ketosis)
Definition
It is a metabolic disorder characterized by a triad
of:
1. Ketonemia (increase ketone bodies in blood).
2. Ketonuria (increase ketone bodies in urine).
3. Acetone (fruity) odor of breath.
There are also dehydration, acidosis, coma, and
death (if untreated).

348. Causes of ketosis
1. Prolonged starvation.
2. Severe dieting.
3. Uncontrolled diabetes mellitus.

349. Mechanism (Pathogenesis) of Ketosis
 In all types of ketosis, there is a decrease in
insulin/glucagon ratio, so there is a defect in carbo-
hydrate metabolism, so the body depends on
oxidation of fat as the main source of energy. so,
there is excessive lipolysis in adipose tissue that
yields large amounts of glycerol and fatty acids.

350.  Also, high fatty acid degradation decreases
NAD+/NADH ratio which slows the CAC cycle.
Consequently, acetyl CoA is diverted to the
pathway of ketogenesis leading to excessive
formation of ketone bodies which are released to
the blood in large amounts leading to ketonemia
and are also excreted in urine in large amounts
leading to ketonuria.

351.  Acetone is a volatile substance and is excreted in
excessive amounts by the lungs in the expired air
resulting in acetone odour of breath. Acetoacetic
acid and -hydroxybutyric acid are moderately
strong acids and they are buffered by the alkali
reserve in the blood (HCO3) and are excreted in
urine in the form of their sodium and potassium
salts resulting in depletion of the alkali reserve
and consequently acidosis (ketoacidosis) and this
can give rise to coma and death.

352. Severe
dieting
Uncontrolled
DM
Mechanism of Ketosis
insulin Glucagon
Lipolysis
Plasma FFA
Prolonged
starvation

353. FA oxidation
Acetyl CoA that can not enter CAC
due to defect in CHO metabolism
Ketogenesis
Ketosis

354. N.B.
 In cases of uncontrolled diaetes mellitus, there is
diminished utilization of glucose by the tissues
due to insulin deficiency. Glucagon will be
increased in the circulation and concomitant rise
of other stress hormones will occur as
epinephrine, norephinepherine, cortisol and
growth hormone. Increased lipolysis will occur in
cases of starvation and increased production of
ketone bodies will occur.

355. Cholesterol Metabolism

356. Cholesterol
 It is the main sterol in the human body.
 It is an alcohol.
 It is often found as cholesterol ester (i.e. in
combination with a fatty acid (usually linoleic aid)
attached to the hydroxyl group at C3.

357. Structure of Cholesterol
.
HO
21 22
20 23
27
26
25
24
3

358. Free Cholesterol is an Amphipathic Molecule
.
HO
21 22
20
23
27
26
25
24
Hydrophilic
(polar) head
3
Hydrophobic (non-polar) hydrocarbon tail

359. Cholesterol Ester
.
R - C - O
21 22
20
23
27
26
25
24
3
O

360. Cholesterol Ester is a Hydrophobic Molecule
.
R - C - O
21 22
20
23
27
26
25
24
Hydrophobic (non-polar)
acyl group
3
Hydrophobic (non-polar) hydrocarbon chain
O

361. Criteria of Cholesterol ester
1. It contains a fatty acid (usually linoleic aid)
attached to C-3 of cholesterol.
2. It is more hydrophobic than free cholesterol.
3. It is not present in membranes.
4. It represents the major fraction of plasma
cholesterol.
5. It is present at low levels in most cells.
361

362. Sources of Cholesterol
 It is formed in the body from acetyl CoA.
 It is present in diet e.g. egg yolk, meat, liver and
brain. (It occurs in animal fats but not in plant
fats).

363. Synthesis of Cholesterol
 Cholesterol is synthesized in the cytosol of all
nucleated cells, so it is not essential to take
cholesterol in diet.
• Major Sites of Synthesis
1. Liver (50%).
2. Intestine (15%).
3. Skin.
4. Reproductive tissues (testis, ovary and placenta).
5. Adrenal cortex.
363

364. Synthesis of Cholesterol (cont.)
 Enzymes
They are present in both the cytosol and the
membrane of the endoplasmic reticulum.
 All the carbon atoms of cholesterol are provided
by acetyl CoA (active acetate)
364

365. Steps of Synthesis of Cholesterol
HOOC - CH2 - C - CH2 - C ~ SCoA
H3C - C ~ SCoA
3-hydroxy-3-methyl glutaryl CoA (HMG CoA)
OH
CH3
H2O
CoASH
O
CH3 - C - CH2 - C ~ SCoA
Acetoacetyl CoA
O O
Acetyl CoA
CH3 - C ~ SCoA
O
Acetyl CoA
Acetyl CoA
CoASH
Thiolase
CH3 - C ~ SCoA
O O
HMG CoA synthase

366. Steps of Synthesis of Cholesterol (cont.)
.
366
Mevalonate
2NADPH+2H+
2NADP+
CoASH
HOOC - CH2 - C - CH2 - CH2 - OH
OH
CH3
HMG CoA reductase
CO2

367. Steps of Synthesis of Cholesterol (cont.)
.
367
Cholesterol
(27 carbons)
Removal of
3 carbons
Isopetenyl pyrophosphate
(5 carbons)
Squalene
(30 carbons)
Condensation
of 6 molecules
3 CH3
X 6
molecules

368. Regulation of Cholesterol Synthesis
- It occurs at the enzyme HMG CoA reductase (rate-
limiting enzyme).
Short-term regulation
(takes minutes or even seconds)
Long-term regulation
(take days or even months)
Allosteric
regulation
Hormonal
regulation

369. Allosteric Regulation
Allosteric effector
or modulator
Positive effector Negative effector
HMG CoA
Reductase
Substrate
Catalytic site
Allosteric site
Allosteric
enzyme

370. Allosteric Regulation of Cholesterol Synthesis
 It is a short-term regulation (takes minutes or even
seconds)
 Dietary cholesterol inhibits HMG CoA reductase
cholesterol synthesis.
370

371. Hormonal Regulation of Cholesterol
Synthesis
 It is a short-term regulation (takes minutes or even
seconds)
 Insulin stimulates HMG CoA reductase by
promoting dephosphorylation of the enzyme
cholesterol synthesis.
 Glucagon inhibits HMG CoA reductase by
promoting phosphorylation of the enzyme
cholesterol synthesis.
371
+

372. Hormonal Regulation of Cholesterol Synthesis
ATP
ADP
HMG CoA
Reductase
H2O
Protein kinase
Phosphoprotein
phosphatase
Inactive Active
HMG CoA
Reductase
P
Glucagon
Pi
Covalent
bond
372
Insulin
+
+

373. Long-Term Regulation of Cholesterol
Synthesis
 It takes days or even months.
 Cholesterol inhibits transcription of HMG CoA
reductase gene cholesterol synthesis.
373

374. Regulation of cholesterol synthesis
- HMG Co A reductase is the rate-limiting enzyme in
cholesterol synthesis.
- HMG Co A reductase is an intrinsic membrane
protein of the endoplsmic reticulum.
- It under control of the following mechanisms:
1. Sterol-dependent regulation of expression of
HMG CoA reductase gene.
374

375. 2. Sterol-accelerated HMG CoA reductase
degradation.
3. Sterol-independent phosphorylation/
dephosphorylation (covalent modification) of
HMG Co reductase.
4. Hormonal regulation of HMG Co reductase.
5. Inhibition by drugs.
375

376. 1. Sterol-dependent regulation of HMG Co A
reductase gene expression
- Low intracellular cholesterol the
transcription factor, SREBP (sterol regulatory
element-binding protein) that binds DNA at the
sterol regulatory element (SRE) of the HMG CoA
reductase gene increased synthesis of HMG
CoA reductase and, therefore, increased
cholesterol synthesis.
- High intracellular cholesterol has opposite effrect.
+
376

377. Regulation of HMG CoA reductase gene expression
by cholesterol and hormones
.
N.B.
SRE: sterol regulatory element
REBP: sterol regulatory element-binding protein (transcriotion factor)
IC: intracellular
mRNA
DNA
HMG CoA reductase
HMG CoA Mevalonate
IC Cholesterol
mRNA
SRE
Transcription
Translation
Cytosol
Nucleus
HMG CoA reductase gene
SREBP
Cholesterol
+
Insulin
Glucagon
377
+
+

378. 2. Sterol-accelerated HMG CoA reductase
degradation
- High intracellular cholesterol degradation of
the HMG CoA reductase by ubiquitin-proteosome
system decreased cholesterol synthesis.
378

379. 3. Sterol-independent phosphorylation/
dephosphorylation (covalent modification) of HMG
CoA reductase
- Adenosine monophosphate-activated protein
kinase (AMPK) and a phosphoprotein phosphatase
carry out phosphorylation and dephosphorylation
of HMG CoA reductase respectively.
- The phosphorylated form of the enzyme is
inactive, whereas the dephosphorylated form is
active. 379

380. N.B.
AMPK is activated by AMP, so cholesterol synthesis
is decreased when ATP level is decreased.
380

381. Covalent modification of HMG CoA reductase
activity of Cholesterol Synthesis
ATP
ADP
HMG CoA
Reductase
H2O Phosphoprotein
phosphatase
Inactive Active
HMG CoA
Reductase
P
AMP
Pi
Covalent
bond
381
+
AMP-activated protein kinase
(AMPK)

382. 4. Hormonal regulation
- Insulin favors up-regulation of the expression
of the HMG CoA reductase gene cholesterol
synthesis.
- Glucagon has the opposite effect.
382

383. 5. Inhibition of cholesterol synthesis by drugs
 Statin Drugs (e.g. simvastatin and lovastatin)
are structural analogs of HMG CoA reductase
reversible inhibition of this enzyme
cholesterol synthesis.
 Statin Drugs are used to decrease plasma
cholesterol levels in patients with hyper-
cholesterolemia. 383

384. Inhibition of cholesterol synthesis by statin drugs
(competitive inhibitors)
CH3
HO
O
C
O
OH
O
O
CH3
HMG CoA reductase
active site
CH3
HO
O
C
O
OH
O
O
CH3
HO
O
C
OH
O
CH3
HMG
(substrate)
Lovastatin
(competitive inhibitor= substrate analog inhibitor)
384

385. Cholesterol in Non-Hepatic Cells
 Nonhepatic cells obtain cholesterol from plasma
low density lipoproteins (LDL) rather than by
synthesizing it de novo.
 LDL binds to specific receptors on the plasma
membrane of non-hepatic cells.
 The receptor LDL complex is internalized by
endocytosis. These vesicles fuse with lysosomes.
385

386. Cholesterol in Non-Hepatic Cells (cont.)
 Inside the lysosomes, cholesterol ester is
hydrolyzed by lysosomal acid lipase to free
cholesterol that is either.
a. used unesterified for biosynthesis of cell
membrane.
b. re-esterified for storage inside the cell by Acyl
CoA-cholesterol Acyl transferase (ACAT) which
is activated by free cholesterol. 386

387. Cholesterol in Non-Hepatic Cells (cont.)
c. In specialized tissues such as adrenal glands
and ovaries, the cholesterol derived from LDL-
serves as a precusrsor of steroid homones e.g.
cortisol and estradiol. In the liver, cholesterol
extracted from LDL and HDL is converted to bile
salts that function in intestinal fat digestion.
387

388. Regulation of Cholesterol Content of Non-
Hepatic Cells
 The cholesterol content of the cells that have an
active LDL pathway is regulated in 2 ways:
1. Suppression of the formation of HMG CoA
reductase by the released cholesterol
de novo synthesis of cholesterol.
388

389. Regulation of Cholesterol Content of Non-
Hepatic Cells
2. Feed back regulation of LDL receptors
When cholesterol is abundant inside the cell, new
receptors are not synthesized and so the uptake
of additional cholesterol from the plasma LDL is
blocked.
N.B.
Absence of LDL receptors leads to hyper-
cholesterolemia and premature atherosclerosis.
389

390. Dynamics of Cholesterol
 Plasma cholesterol is in a dynamic state.
 It enters the blood complexed with plasma
lipoproteins; mainly low-density lipoproteins (LDL)
and high-density lipoproteins (HDL) and leaves the
blood as tissues remove cholesterol from these
lipoproteins or degrade them intracellularly.
390

391. Dynamics of Cholesterol (cont.)
Cholesterol occurs in lipoproteins in 2 forms:
a. Free cholesterol (30%)
It is the form of cholesterol that exchanges
between different lipoproteins and plasma
membranes of cells.
b. Esterified cholesterol (70%)
It is esterified with long chain FAs mainly linoleic
acid.
391

392. Dynamics of Cholesterol (cont.)
 HDL and the enzyme lecithin-cholesterol acyl
transferase (LCAT) play important roles in the
transport and elimination of cholesterol from the
body.
 LCAT is a plasma enzyme produced mainly by the
liver. The actual substrate for LCAT is cholesterol
contained in HDL.
392

393. Dynamics of Cholesterol (cont.)
 LCAT catalyses the irreversible reaction which
transfers the fatty acid in the 2nd position of
phosphatidyl choline to the 3-hydroxyl group of
cholesterol.
 The LCAT-HDL system functions to protect cells
especially their plasma membranes from the
damaging effects of excessive amounts of free
cholesterol.
393

394. Phosphatidyl choline (Lecithin)
O
1
2
3
CH2 - O - C – R1
CH - O - C – R2
CH2 - O - P - O - CH2 - CH2 - N(CH3)3
O
OH
O

395. Lecithin - Cholesterol Acyltransferase; LCAT
(Phosphatidyl choline - Cholesterol Acyltransferase;
PCAT
Phosphatidyl choline (Lecithin)
- amphipathic
Cholesterol
- Amphipathic
- On the surface
of HDL
Phosphatidyl choline
(lecithin) - cholesterol
acyltransferase
(PCAT or LCAT)
Lysoophosphatidyl choline
(lysolecithin)
Cholesteryl ester
- Hydrophobic
- Moves to the interior
of HDL

396. Dynamics of Cholesterol (cont.)
 Cholesterol ester generated in LCAT reaction
diffuse into the core of HDL particle where it is
then transported from the tissues and plasma to
the liver; which is the only organ capable of
metabolizing and excreting cholesterol.
 By this mechanism (reverse cholesterol transport),
LCAT acting on HDL provides a way for the
transport of cholesterol from peripheral tissues to
the liver.
396

397. Biomedical importance of Cholesterol
1. It is the main sterol in human body;
a. It is a component of the nervous tissue, brain,
suprarenal gland, and bile.
b. It is a major constituent of the plasma
membrane.
2. It is the precursor of sex hormones, cortical
hormones, vitamin D and bile acids and salts.

398. Disposal of cholesterol
- The ring structure of cholesterol can not be
catabolized to CO2 and H2O in humans.
- Cholesterol passes to liver and undergoes the
following fates:
Conversion to
bile acids and bile salts
Excreted in feces
Secretion
in bile as cholesterol
Transported to intestine
Excreted in feces
as cholesterol
Reduced by bacteria to neutral sterols
(coprostanol and cholestanol) which are
excerted in feces
398
Transported to intestine

399. Bile acids
Secondary bile
acids
Primary bile
acids
Intestine
Liver
Site of synthesis
Primary bile
acids
Cholesterol
Precursor
Deoxycholic
acid &
lithocholic acid
Cholic acid &
chenodeoxy-
cholic acid
Example
399

400. Structure of primary bile acids
24
11
7
3
3 7
Cholic acid
Chenodeoxycholic acid
400

401. Structure of secondary bile acids
24
11
3
3
Deoxycholic acid
Lithocholic acid
401

402. Synthesis of primary bile acids
(e.g. cholic acid)
.
24
7
24
402

403. Properties of bile acids
1.They are amphipathic molecules because they
have both hydrophilic (polar) portion (made by the
carboxyl group and the hydroxyl groups that are β
in orientation i.e. lie above the plane of the rings)
and hydrophobic (non polar) portion (made by the
rings and the methyl groups that are α in
orientation i.e. lie below the plane of the rings).
403

404. 2. They are transported in blood bound non-
covalently to plasma albumin.
404

405. Bile acids are amphipathic molecules
.
Hydrophilic head
Hdyrophobic tail
Bile acid molecule
405

406. Function of bile acids
They act as emulsifying agents so they help the
digestion of dietary lipids by pancreatic enzymes.
406

407. Synthesis of primary bile salts
. Cholic acid
(primary bile acid)
Chenodeoxycholic acid
(primary bile acid)
+ Glycine
+ Glycine
+ Taurine
Glycocholic acid
(primary bile salt)
Glycochenodeoxycholic acid
(primary bile salt)
Taurocholic acid
(primary bile salt)
+ Taurine
Taurochenodeoxycholic acid
(primary bile salt)
407
In Liver In Liver

408. Synthesis of secondary bile acids and salts
. Primary bile salts
Primary bile acids
(cholic acid & chenodeoxycholic acid)
Secondary bile acids
(deoxyCholic acid & lithcholic acid)
Secondary bile salts
Glycine or taurine Deconjugation by intestinal bacteria
Dehydroxylation by intestinal bacteria
Glycine or taurine
Conjugation in Liver
408

409. Functions of Bile Salts
1.They activate pancreatic lipase, so they help the
digestion of lipids.
2.They are strong emulsifying agents so they help
the digestion of dietary lipids by pancreatic
lipase.
3.They have hydrotropic properties i.e. they make
water-insoluble compounds more soluble in
aqueous solution through the formation of
409