Biochemistry focused on lipid and its metabolism

1. 1
Lipids and It’s Metabolism
By:
Abebe Dukessa Dubiwak (MSc in Medical Biochemistry, Ph.D. fellow)
Email: dubiwak.2020@gmail.com

2. Outline
1. Definition of Lipids
2. Classification of Lipids
3. Triglycerides
4. Lipid digestion, absorption and transports
5. TAG synthesis and degradation
6. Fatty acids oxidation/ beta oxidation
7. Lipoproteins/plasma lipoproteins
8. Disorders associated with lipid metabolism
2

3. Introduction
Lipids :- are a heterogeneous group of compounds composed of
carbon, Hydrogen and Oxygen, which are insoluble in water but
soluble in non-polar solvents such as chloroform, ether and benzene.
certain lipids will not come under this definition.
e.g. derived lipids like fatty acids are relatively soluble in water.
They are esters of long chain fatty acids and alcohols.
General classification
•Fats- Fats are defined as lipids which exist as solid at ordinary
temperature
E.g. Animal fat
•Oils- Oils are defined as lipids which exist as liquid at
ordinary temperature.
E.g. Cooking oil (vegetable oil).
3

4. Classification of Lipids
Lipids
Simple lipids Compound lipids Derived lipids
1. Neutral fat(TAG) 1. Phospholipids 1.Fatty acids
2. Waxes 2. Glycolipids 2. Steroids(cholesterol)
3. Aminolipids etc. 3. Glycerol etc.
4

5. Triglycerides（triacylglycerols）,Called “Neutral Fats”
- made of 3 free fatty acids and 1 glycerol
- FFA 4-22 Carbons long (mostly 16-20)
- 95% of dietary lipids (fats & oils)
Triglyceride
Glycerol + 3 FFA TG + H2O
5

6. STRUCTURE TRIGLYCERIDES
• Triglyceride - three fatty acids attached to a glycerol
backbone
• Diglyceride – two fatty acids +glycerol
• Monoglyceride – one fatty acid +glycerol
6
Fatty Acids
Triglyceride

7. Food Triglycerides Contain a Variety of Fatty Acids
• Monounsaturated fatty acids are abundant in olive, peanut, and
canola oils.
• Omega-6 polyunsaturated fatty acids are abundant in safflower,
corn, and sunflower oils.
• Omega-3 polyunsaturated fatty acids are most abundant in fish
and seafood, nuts, and some vegetable oils.
• Saturated fatty acids are high in meats and tropical palm and
coconut oils.
7

8. • Omega-3 Fatty Acid – double bond at carbon 3
• Omega-6 Fatty Acid – double bond at carbon 6
• Omega-9 Fatty Acid – double bond at carbon 9
*count carbons from the methyl (omega) end
8
• Omega 3
• Omega 6
• Omega 9

9. FATTY ACIDS
I) Nonessential Fatty Acids – our body can make certain fatty
acids so they are not required in the diet
II) Essential Fatty Acids – our bodies cannot make C-C double
bonds before the 9th carbon from the methyl end, so we must get
these fatty acids from our diet
 EFAS = omega-6 linoleic acid & omega-3 alpha-linolenic acid
9

10. Essential Fatty Acids (fish)
 Essential fatty acids (to date):
– linoleic (18:2 ῳ-6)
– linolenic (18:3 ῳ-3 fish)
– arachidonic (20:4 ῳ-6)
– eicosopentaenoic acid(EPA)(20:5 ῳ-3)
– Docosohexaenoic acid(DHA) (22:6 ῳ-3)
10

11. Manifestations of EFAs deficiency
- Cessation of growth
- Skin lesion,loss of complexion (Acanthosis = hypertrophy of prickle
cells & hyperkeratosis= hypertrophy of stratum corneum.
- Skin becomes abnormally permeable to water.
- Increased loss of water even during BMR.
- fatty liver,Kidney damage
- Abnormality of pregnancy & lactation etc
11
Acanthosis
Hyperkeratosis
8/17/2022

12. 12
2. Complex lipids:
These are esters of fatty acids containing other groups in addition
to alcohol and fatty acids;- Phospholipids, Glycolipids, & Others
3. Precursor and derived lipids:
These are derived from the hydrolysis of above two classes of
lipids;- Fatty acids, steroids, ketone bodies, lipid-soluble vitamins,
etc.

13. What is a phospholipid?
• A phospholipid is triglyceride in which one fatty acid has been
replaced by a phosphate group.
• The phosphate group is soluble in water, while the fatty acid
“tails” are not.
• Phospholipids are thus hydrophilic at one end and
hydrophobic at the other end, making them useful for
emulsifying and packaging lipids and for building cell
membranes.
13

14. Phospholipids
• Structure
– Glycerol + 2 fatty acids +
phosphate group
• Functions
– Component of cell
membranes
– Lipid transport as part of
lipoproteins
• Food sources
– Egg yolks, liver, soybeans,
peanuts
14

15. What are sterols?
• Sterols are a family of molecules consisting of
interconnecting carbon rings.
• The most common form of sterol in the human body is
cholesterol.
15

16. What are the sources and importance of Cholesterol the
human cells ?
 The sources of cholesterol for the cells.
I. Endogenous (Cells can synthesize cholesterol from acetyl CoA)
II. From dietary( e.g - meat, milk, butter, eggyolk)
 Cholesterol is needed
 Components of cell membranes
 Cholesterol esterification for transfer from one lipoprotein
(HDL) to other lipoproteins (VLDL, IDL & LDL)
 Bile acid synthesis w/c important for digestion of dietary fat
 precursor for vitamin-D3(Provitamin D)
 Steroid hormone synthesis
• Androgens(sex hormone)
• Estrogens(sex hormone)
• Corticosteroid
• Glucocorticoids 16

17. Structure of Cholesterol
HO
CH3
H
H
H
CH3
CH3 CH3
CH3
Fundamental framework of steroids
Structure of Cholesterol
A B
C D
1
2
3
4
5
6
7
8
9
10
11
12
13
14 15
16
17
18
19
17

18. 18
Steroids
A. Cholesterol
HO cholesterol
squalene
sex hormones
glucocorticoid hormones
mineralocorticoid hormones
bile acids
acetic acid
isopentenyl
pyrophosphate

19. 19
 Site of Cholesterol Synthesis:
 mainly in liver(75-80%), intestine, gonads & skin.
 Low amount in: Adipose tissue, muscle, aorta & neural
tissues.
 Brain of newborn can synthesize cholesterol but not adults’.
 Acetyl-CoA is the starting material(all 27C are from acetate).
 ~1g/day is synthesized(endogenous cholesterol) from acetyl
CoA.
 Acetyl CoA from pyruvate oxidation & Fatty Acids oxidation.
Cholesterol

20. 20
Steroids
B. Bile acids
 Synthesized (produced) from the cholesterol in the liver,
stored in the gall bladder, secreted into the intestine
 help to emulsify dietary fats and aid in their digestion
HO OH
OH
CO2
-
cholic acid

21. 21
A. Primary bile acids:- synthesized in liver from cholesterol
1.Cholic acid(main acid in bile) & 2.Chenodeoxy cholic acid.
B. Secondary bile acids:
 produced in intestine from primary bile acids by the action
of intestinal bacteria.
1.Deoxycholic acid: from cholic acid.
2.Lithocholic acid: from chenodeoxycholic acid.
Bile Acids

22. 22
Bile Acids

23. 23
1.Emulsification of fats( facilitate digestion)
2. Micelles formation
3.Absorption of fat soluble Vitamins & carotene.
4.Have Choleretic action;-stimulate liver to secrete bile.
5. keep cholesterol in solution(in gallbladder).
Functions of Bile Salts

24. 1. Digestion and transport of dietary lipids
2. Synthesis of TAG
3. Catabolism of TAG
4. Beta oxidation
5. Lipogenesis: Fatty Acid Synthesis
24

25. 1. Digestion of dietary lipids
25

26. 26
 Globules of fat need to be: Emulsified before digestion can take
place
 Fat globules: Hydrophobic nature excludes water-soluble
enzymes, Also present limited surface area for enzyme action
 This is why an emulsification process needs to take place before
digestion can begin
 Emulsification: breakdown of large fat globules into smaller
ones; in Mouth by chewing, in Stomach by gastric contraction,
in Intestine by peristalsis, bile salts & phospholipids
1.Digestion of dietary lipids

27. Action of Bile Salts
27
 Dietary fat leaves the stomach and enters the Small Intestine(SI),
where it is emulsified by bile salts
 Cholecystokinin (CCK):- is the gut hormone secreted by the
intestinal cells when dietary fat enter the SI from the stomach.
 Then it stimulates:- contraction of the gallbladder to secrets
bile salts & secretion of pancreatic enzymes
 The bile salts are amphipathic compounds:- containing both
hydrophobic & hydrophilic components
 synthesized in the liver and secreted via the gallbladder into
the intestinal lumen

28. 28
 Bile salts act as detergents,
 binding to the globules of dietary fat as they are broken
up by the peristaltic action of the intestinal muscle
 Also they shift the PH from 8 to 6.5
 This emulsified fat,
 which has an increased surface area as compared with
unemulsified fat is attacked by digestive enzymes from
the pancreas
Action of Bile Salts

29. Figure 5-13 Emulsification of fat by bile
©2001 Brooks/Cole, a division of Thomson Learning, Inc. Thomson Learning™ is a trademark used herein under license.
29

30. 30
Figure: Action of bile salts. The hydrophobic portions of bile salts intercalate
into the large aggregated lipid, with the hydrophilic domains remaining at the
surface. This leads to breakdown of large aggregates into smaller and smaller
droplets. Thus the surface area for action of lipase is increased

31. Digestion & absorption of TAGs
31
 The main route for digestion of TAG involves:
 Hydrolysis to fatty acids & 2-Monoacylglycerols in the
lumen of the intestine
 However, the route depends to some extent on the
chain length of the FAs
 Lingual & gastric lipases are produced by:-cells at the back of
the tongue & in the stomach, respectively
 these lipases preferentially hydrolyze short- & medium-
chain FAs
 They are most active in infants & young children who drink
relatively large quantities of cow’s milk, which contains TAGs
with a high percentage of short- & medium-chain FAs

32. 32
Digestion of TAGs

33. Absorption of Dietary Lipids
 The FAs & 2-MGs produced by digestion are
packaged into micelles, tiny microdroplets
emulsified by bile salts
 Other dietary lipids, such as
• CL, lysophospholipids, & fat-soluble vitamins
 also packaged in these micelles
 The micelles travel through a layer of water to
• the microvilli on the surface of the intestinal
epithelial
where the FAs, 2-MGs, & other dietary lipids are
absorbed
but the bile salts are left behind in the lumen of the
gut
 The bile salts are extensively reabsorbed
• when they reach the ileum
33

34. 34
Fig. Recycling of bile salts

35. Fig- Digestion of TAG in the
intestinal lumen

36. Lipid mal-absorption (steatorrhea):
Lipid mal-absorption (steatorrhea):
• Is the loss of > 6g of fat together with
– fat soluble vitamins (A,D,E,K) and
– essential fatty acids.
Causes of steatorrhea:
1. Defective digestion
 due to deficiency of pancreatic lipase
 as a result of chronic pancreatits,
 cystic fibrosis and
 severe gastric hyperacidity.
 Feacal fat is mostly undigested TAGs.
36

37. 2.Defective absorption
A. due to deficiency of bile salts
 as a result of bile duct
obstruction
 Feacal fat is in the form of 2-
monoacylglycerol.
B.due to defective intestinal mucosal
cells
 as in shortened bowel (by
surgical removal) and
 coeliac diseases such as sprue.
37
Lipid mal-absorption (steatorrhea):

38. 2. The synthesis of TAG
1. Mono-acylglycerol pathway (MAG pathway)
(for dietary fat digestion and absorption)
pancreatic
lipase
FA
pancreatic
lipase
FA
ATP,CoA
acyl CoA acyl CoA
intestinal epithelium
intestinal lumen
Chylomicrons
lymphatic vessels
adipose tissue
CH2OCOR
CHOCOR
CH2OCOR
TAG
CH2OH
CHOCOR
CH2OCOR
DAG
CH2OH
CHOCOR
CH2OH
MAG
CH2OH
CHOCOR
CH2OH
MAG
CH2OCOR
CHOCOR
CH2OCOR
TAG
FA FA
38

39. 2. Diacylglycerol pathway (DAG pathway)
(for TAG synthesis of in adipose tissue, liver and kidney)
CH2O-PO 3H2
CO
CH2OH
dihydroxyacetone
phosphate
liver
adipose tissue
NADH+H+
NAD+
phosphoglycerol
dehydrogenase CH2O-PO 3H2
CHOH
CH2OH
3-phosphoglycerol
ADP ATP
glycerol kinase
liver
kidney
RCO¡«SCoA
HSCoA
CH2O-PO3H2
CHOH
CH2OCOR
lysophosphatidate
acyl CoA transferase
acyl CoA
transferase
RCO¡«SCoA
HSCoA
phosphatidate
CH2O-PO 3H2
CHOCOR
CH2OCOR
H2O
Pi
CH2OH
CHOCOR
CH2OCOR
diacylglycerol
RCO¡«SCoA
HSCoA
acyl CoA
transferase
glucose
CH2OH
CHOH
CH2OH
glycerol
CH2OCOR
CHOCOR
CH2OCOR
triacylglycerol
phosphatase
39

40. 40
3. Catabolism of TAG (Mobilization of Fatty acids from
adipocytes)
 Fatty acids are stored for future use as TAG in all cells but
primarily in adipocytes of adipose tissues.
 TAG plays an important role in furnishing energy in animals.
When the energy supply from the diet is limited, the body
responds to this deficiency through the secretion of hormones like
glucagon, epinephrine or adrenocorticotropic hormones

41. 41
 These hormones activate an enzyme called hormone sensitive
triacylglycerol lipases.
 These lipases hydrolyze the triacylglycerol at C#1 or C#3 to
produce diacylglycerol and a fatty acid.
 Diacylglycerol lipases hydrolyze the diacylglycerol to
monoacylglycerol and a fatty acid.
 Finally Monoacylglycerol lipases hydrolyze monoacylglycerol to
fatty acid and glycerol.
 This is called as mobilization of fatty acids.
Mobilization of Fatty acids from adipocytes

42. Mobilization of
triacylglycerols
stored in
adipose tissue
glucagon
42

44. Glycerol:
This glycerol is transported through the blood to the liver where
it may undergo different fates:-
1- which can be converted
• to glucose by gluconeogenesis or
• pyruvate by the glycolysis sequence of reactions.
2- glycerol may be phosphorylated to glycerol-3-phosphate,
 which can be used to synthesize fats.
44
Fate of the glycerol and Fatty acids obtained during TAG
degradation

45. 45
FATTY ACIDS:
 Most of the fatty acids present in fats have a very long chain
that makes them insoluble in water.
 Therefore they are transported in the blood bound to
albumin, taken to other tissues like the liver, kidney,
muscles, mammary glands, intestine, adipose tissues &
heart
 where they are used as fuel.

46. 46
4. BETA OXIDATION OF FATTY ACIDS
 -oxidation of FA is: the principal pathway for the catabolism of
FA
 two carbon fragments are successively removed from the carboxyl
end of the fatty acid, producing acetyl CoA.
 Site: Mitochondrial matrix of tissues .
 Steps in ß –Oxidation
 Fatty Acid Activation by esterification with CoASH
 Membrane Transport of Fatty Acyl CoA Esters
Dehydrogenation
Hydration
Dehydrogenation
Thiolase Reaction (Carbon-Carbon Cleavage)

47. 47
 Step I-Activation of FA
 As the priming step for their catabolism, the FAs are:
 activated to their CoA derivative,
 using adenosine triphosphate (ATP) as the energy source
 Fatty acid + ATP + CoA Acyl-CoA + PPi + AMP
ß -Oxidation occurs in the mitochondria;

48. Fatty Acid Transport into Mitochondria
Fats are degraded into fatty acids and glycerol in the
cytoplasm
-oxidation of fatty acids occurs in mitochondria
Small (< 12 carbons) fatty acids diffuse freely across
mitochondrial membranes
Larger fatty acids are transported via acyl-carnitine/
carnitine transporter
48

49. 49

50.  The -Oxidation
Pathway:
1)Dehydrogenation
2)Hydration
3)Dehydrogenation
4)Thiolase Reaction
Each pass removes
one acetyl moiety in
the form of acetyl-
CoA
50

51. -Oxidation and ATP
Activation of a fatty acid requires:
2 ATP
One cycle of oxidation of a fatty acid produces:
1 NADH 3 ATP
1 FADH2 2 ATP
Acetyl CoA entering the citric acid cycle produces:
1 Acetyl CoA 12 ATP
51

52. ATP for Myristic Acid C14
ATP production for Myristic(14 carbons):
Activation of myristic acid -2 ATP
7 Acetyl CoA
7 acetyl CoA x 12 ATP/acetyl CoA 84 ATP
6 Oxidation cycles
6 NADH x 3ATP/NADH 18 ATP
6 FADH2 x 2ATP/FADH2 12 ATP
Total 112 ATP
52

53. Summary of Catabolism( OXIDATION) of Lipids
• Quantitatively β oxidation of fatty acids is the most important
pathway which occurs in the mitochondria
• Each cycle of β oxidation of fatty acids have 4steps
Dehydrogenation, hydration, dehydrogenation & cleavage.
• It’s the most important pathway for fatty acid oxidation.
• In β oxidation 2 c atoms are cleaved at a time from fatty
acylCoA molecules starting at the COOH end.
53
CH2 C
O
O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
1
2
3
4
5
6
7
1 2 3 4 5 6 7
8

54. Overall Per Beta Oxidation cycle
• 1 FADH2…………………………2ATP
• 1 NADH………………………….3 ATP
• 1 Acetyl CoA to Krebs……..12ATP
54

55. Beta Oxidation on 16 C fatty Acid
CH2 C
O
O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
1
2
3
4
5
6
7
1 2 3 4 5 6 7
8
7 rounds of Beta oxidation (bottom numbers)
Form 8 acetyl Co A (top numbers)
55

56. Oxidation of fatty acids produces a large quantity of ATP:
Palmitoyl CoA + 7 FAD + 7 NAD+ + 7 CoA + 7H2O 8 acetyl
CoA + 7 FADH2 + 7 NADH + 7 H+
Oxidation of NADH - 3ATP
'' FADH2 - 2 ATP
'' Acetyl-CoA - 12 ATP
7 FADH2 yields =14
7 NADH yields =21
8 acetyl-CoA yields =96
Total 131 ATP
2 high energy phosphate bonds are consumed in the activation
of palmitate
Net yield is 129 ATP or 129 X 51.6 = 6656 kJ
56

57. Beta Oxidation basically contains 4 reactions:
Dehydrogenation, Hydration, Dehydrogenation. Cleavage
Each pass through beta oxidation removes 2 carbon atoms
from fatty acids
And produces one molecule of FADH2 and one molecule of
NADH which produces 5 molecules of ATP in Electron transport
chain
Palmitoyl COA + 7FAD +7 NAD +7 H2O 8 Acetyl CoA +7
FADH2+ 7 NADH+ 7H+
 Energy yield– For the complete oxidation of palmitic acid
(16:0) seven beta oxidation cycles are required. They
produce 8 molecules of Acetyl CoA, 7 mol. Of FADH2 and 7
mol of NADH+H+
57

58. Ketone Bodies
 Starvation causes accumulation of acetyl CoA
 not enough carbohydrates to keep Kreb’s Cycle going
 acetyl CoA forms acetoacetate, beta-hydroxybutyrate, and
acetone.
58
Ketone Bodies - formed in the
liver and oxidized in skeletal
and heart muscle and the
renal cortex. Brain adapts to
use them under starvation
conditions

59.  Acetyl-CoA in liver mitochondria is converted to ketone
bodies:-
 It resulted ketone bodies are Acetoacetate, Acetone, β-hydroxy
butyrate
 High concentration of ketone bodies can induce ketonemia and
ketonuria, and even ketosis and acidosis
 When carbohydrate catabolism is blocked by a disease of
diabetes mellitus or defect of sugar source, the blood
concentration of ketone bodies may increase, the patient may
suffer from ketosis and acidosis
59

60. Diabetes and Ketone Bodies
 When there is not enough insulin in the blood and it must
break down fat for its energy.
 Ketones build up in the blood and then spill over into the
urine so that the body can get rid of them.
 Acetone can be exhaled through the lungs.
 This gives the breath a fruity odor.
 Ketones that build up in the body for a long time lead to
serious illness and coma(Diabetic ketoacidosis , DKA)
60

61. Diabetic ketoacidosis (DKA)
 Diabetic ketoacidosis (DKA):- is a potentially life-threatening
complication in patients with diabetes mellitus. It happens
predominantly in those with type 1 diabetes, but it can occur in
those with type 2 diabetes under certain circumstances.
 DKA results from a shortage of insulin; in response the body
switches to burning fatty acids and producing acidic ketone
bodies that cause most of the symptoms and complications.
 Typical symptoms of DKA are;- Vomiting, dehydration, deep
gasping breathing, confusion and occasionally coma are.
 DKA is diagnosed with blood and urine tests; it is distinguished
from other. 61

62. Cont…
 Ketoacidosis results from prolonged ketosis:
 Ketonemia- higher than normal quantities of ketone bodies in
blood
 Ketonuria- higher than normal quantities of ketone bodies in
urine.
 Ketosis: the overall condition is called ketosis
 There are three principal causes of ketosis:
1. Diabetes mellitus
2. Starvation periods
3. A rich fat and free carbohydrate diet.
62

63. Lipoproteins
1. Chylomicrons(CM)
2. Very-Low-Density Lipoprotein(VLDL)
3. Intermediate-Density Lipoprotein(IDL)
4. Low-Density Lipoprotein(LDL)
5. High-Density Lipoprotein(HDL)
63

64. Plasma lipoproteins
 Lipoproteins is the molecular complexes of lipids and specific
proteins.
 The proteins that integrated with lipoproteins is called
apolipoproteins or apoproteins e. g Apo B-48, Apo B-100,
Apo C-II, Apo E etc.
 Lipoprotein particles include:
1. Chylomicrons.
2. Very low density lipoproteins (VLDL)
3. Low density lipoproteins (LDL).
4. High density lipoproteins (HDL).
64

65. Plasma lipoproteins
 Lipoproteins function to
 keep lipids soluble as
they transport them in plasma, and
provide an efficient mechanism for
o delivering their lipid contents to the tissues
 The principal lipids carried by lipoprotein particles are
• TRIACYLGLYCEROLS and
• CHOLESTEROL (free or esterified) .
 lipoproteins are composed of
 a neutral lipid core containing triacylglycerol and
 cholesteryl esters or both,
surrounded by :
o apolipoproteins (apoproteins),
o phospholipid and
o non-esterified cholesterol 65

66. Apolipoproteins (Apoproteins)
 The apo-lipoproteins functions including:
 Serving as structural components of the particles.
 Providing recognition sites for cell – surface receptors.
 Serving as activators in lipoprotein metabolism.
 Apolipoproteins are divided by
 structure and function into classes A to H
with most classes having sub-classes for example,
apo A- I and apo C- II.
66

67. Types of lipoproteins:
 Chylomicrons:
 Site of synthesis: Intestinal mucosa.
 Function: They carry triglyceride, cholesterol ester and phospholipids
from the intestine to the peripheral tissues.
 Main lipid component: triglycerides.
 The TAG is degraded by lipoprotein lipase after activated by Apo C-II.
 Major apoliproteins: Apo-A, B48, C(I,II,III) & E
 Very low density lipoproteins (VLDL):
 Site of synthesis: Liver
 Function: It carries triglycerides from the liver to extrahepatic tissues.
 Main lipid component: triglycerides.
 The TAG is exchange with Cholesterol esters from HDL then VLDL
change into IDL eventually convert into LDL in the circulation
 Major apoliproteins: Apo-B100, C(I,II,III) , E
67

68. Types of lipoproteins:
 Low density lipoprotein (LDL)
 Site of synthesis: It is synthesized from VLDL in the
circulation and also in the liver.
 Function: It carries cholesterol to various peripheral tissues.
 Main lipid component: Cholesterol.
 Major apoliproteins: Apo-B100
 High density lipoprotein (HDL):
 Site of synthesis: Intestine and Liver.
 Function: It carries cholesterol from peripheral tissues
(including arteries) to the liver to be catabolized, this is called
reverse cholesterol transport.
 Main lipid component: Cholesterol ester and phospholipids.
 Major apoliproteins: Apo-A, C(I,II,III) , D & E
68

69. 69
Fig. Transfer of proteins from HDL to
chylomicrons.

70. 70
Fig-D8. Fate of Chylomicrons

71. The five classes of lipoprotein
Class Source and function
Major
apoliproteins
Chylomicrons
(CM)
Intestine. Transport of
dietary TAG
A, B48, C(I,II,III) E
Very low density
lipoproteins
(VLDL)
Liver. Transport of
endogenously
synthesised TAG
B100, C(I,II,III) , E
Low density
lipoproteins
(LDL)
Formed in circulation
by partial breakdown
of IDL. Delivers
cholesterol to
peripheral tissues
B100
High density
lipoproteins
(HDL)
Liver. Removes “used”
cholesterol from tissues
and takes it to liver.
A, C(I,II,III), D, E
Increasing
density
71

72. Fig. Molecular Structure & Composition of a Typical Chylomicrons

73. • Chylomicrons are lipoproteins 73

74. Lipoprotein structure
74

75. 75
Lipoproteins and lipid transport

76. Disorders of associated with plasma lipid metabolism
1. Type I hyperlipidemia ( familial hyperchylomicronemia)
 In normal condition lipoprotein lipase cleave FA from TAG of
Chylomicron(CM) after activated by apo c-II w/c component of CM
 Patients with Type I hyperlipidemia is due;
 deficiency of lipoprotein lipase or apo C-II
 Manifested by dramatic accumulation of TAG- rich lipoproteins
in the plasma
2. Type II hyperlipidemia (familial hyperbeta lipoproteinemia).
 Also known as familial hypercholesterolemia
 In normal condition LDLs after binding their receptor the LDLs
are internalized by endocytosis.
 Patients with Type II hyperlipidemia is due
 A deficiency of functional LDL receptors causes/manifested
 a significant elevation in plasma LDL and therefore of plasma
cholesterol elevation.
 This can greatly accelerate the progress of atherosclerosis. 76

77.  VLDLs Metabolism
 VLDL is produced in the liver; composed predominantly of TAG
and carry this lipid from the liver to peripheral tissues.
 Fatty liver disease occurs in conditions
 Imbalance between
o Hepatic TAG synthesis and
o The secretion of VLDL.
o Diseases such as
 hepatitis
uncontrolled DM and
chronic ethanol ingestion can cause fatty liver.
 Deficiency of HDL leads to accumulation of cholesterol in the tissues
(Tanger’s disease)
3. Fatty liver disease & Tangier’s Disease

78. Summary
• Fats are an important energy source in animals
• Two-carbon units in fatty acids are oxidized in a four-step -
oxidation process into acetyl-CoA
• In the process, lots of NADH and FADH2 forms; these can yield
lots of ATP in the electron-transport chain
• Acetyl-CoA formed in the liver can be either oxidized via the
citric acid cycle or converted to ketone bodies that serve as
fuels for other tissues
• Plasma lipoproteins metabolism and their disorders
In this chapter, we learnt that:
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79. THANK YOU!!!
To burn fat, you need carbohydrates!!!
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