All of the pharmacy and Health students use the materials

1. LIPIDS
1

2. Introduction: Lipid
• Lipids comprise very heterogeneous group of
compounds
- insoluble in water (hydrophobic)
-Soluble in non-polar organic solvents such us
benzene, chloroform, and ether.
-present in all living organisms.
- includes fats, oils, waxes and related
compounds.
2

3. Lipid: Functions
• Efficient energy sources.
• Thermal insulators.
• Structural components of the cell membrane.
• Serve as precursors for hormones (steroid
hormones).
• Dissolve fat-soluble vitamins, and assist their
digestion.
• Important group of antigens of parasites
• Some saturated fatty acids are anti-microbial
and anti-fungal agents.
3

4. Classification of Lipids
Simple lipids

5. A- Triacylglycerol
glycerol + 3 fatty acid side chains (R1, R2, R3)
CH2-COO-R1
|
R2-COO-CH
|
CH2-COO-R3
The major storage form of fatty acids is as triacylglycerides

6. A phosphatidic acid: the simplest phospholipid
B- Phosphoacylglycerol
CH2
CH
CH2 -O- P-O-
O
O
O
O
O
O-
glycerol
palmitic acid
stearic acid
The major components of membranes in most species.

7. B- Phosphoacylglycerol (Cont.)
Name and Formula Name of Phospholipid
ethanolamine
+
choline phosphatidylcholine
(lecithin)
phosphatidylethanolamine
(cephalin)
serine phosphatidylserine
NH3
+
- OCH2 CHCO2
-
- OCH2 CH2 N( CH3 ) 3
- OCH2 CH2 NH2

8. B- Phosphoacylglycerol (Cont.)
CH2
inositol phosphatidylinositol
HO
-O
OH
OH
OH
HO
- OCH2 CHCH2 OH
glycerol
phosphatidylglycerol
OH
- OCH2 CHCH2 OPOCHOCR2
OH
O-
O O
O
diphosphophaticylglycerol
(cardiolipin)
CH2 OCR1

9. C- Sphingolipids
Sphingolipids (components of membranes and
insulate nerve fibers)(sphingosine backbone)
Their structures are derived from sphingosine + fatty
acid + phosphate
OH
( CH2 ) 12 CH3
HO
NH2
Sphingosine
Sphingosine is a C18
amino alcohol with an
unsaturated bond in the
C18 chain

10. OH
( CH2 ) 12 CH3
HO
NHCR
(Ceramide: N-acylsphingosine)
O
C- Sphingolipids (cont.)
Ceramide:
A fatty acid attached
via an amide bond to
the amino group on
sphingosine
Sphingomyelin:
A ceramide with addition
of a phosphocholine
group onto the C-1
hydroxyl group
OPOCH2 CH2 N( CH3 ) 3
( CH2 ) 12 CH3
HO
NHCR
A sphingomyelin
O
O
O-
+

11. Glycolipids: a compound in which a carbohydrate
is bound to an -OH of the lipid
• Their Structure = sphingosine + fatty acid + sugar
• The glycolipids are derivatives of sphingolipids
– Many glycolipids are derived from ceramides
– Cerebrosides (simple monosaccharide)
– Gangliosides (complex polysaccharide)
Sulfolipids: they are cerebrosides in which a sulfate
group is attached to galactose of the glycolipid
Lipoproteins

12. D- Eicosanoids
I- Prostanoids
II-
They are compound derived from polyunsaturated
acid containing 20 carbon atoms

13. Structure and properties of fatty acids
FATTY ACIDS
• Long-chain hydrocarbon molecules containing a
carboxylic acid moiety at one end.
• Building block of most lipids
• Not found free in nature but found as esterified
forms
• Most naturally occurring fatty acids have got even
number of carbons.
• Mostly the double bond occurs at the 9th carbon as
we count from the carboxyl group end.
13

14. Structure and properties of fatty acids
• Based on the nature of hydrocarbon side chain,
they are divided into:
A. Saturated
• In which hydrocarbon side chain is saturated
(no double bonds).
B. Unsaturated
• In which hydrocarbon side chain is unsaturated
(one or more double bonds are present).
14

15. Structure and properties of fatty
acids
15
saturated: CH3-(CH2)n-COOH
unsaturated: CH3-CH=CH-(CH2)n-COOH
polyunsaturated: CH3-CH=CH-CH2-CH=CH-(CH2)n-COOH
(Essential FA )

16. Essential Fatty Acids
• Must be obtained from diet.
• Also called poly unsaturated fatty acids (PUFA)
• Includes linoleic acid (LA), linolenic acid (LNA) and
arachidonic acid (AA).
• Arachidonic acid is semi essential fatty acid because
it can be synthesized from the above two essential
fatty acids
16

17. Fatty acids: Functions
• Membrane PL contains essential fatty acids
• Synthesis of PL, cholesterol ester and
lipoproteins
• PUFAs are released from membranes, diverted
for the synthesis of prostaglandins, leukotriens
and thromboxanes.
• They act as fat mobilizing agents in liver and
protect liver from accumulating fats (fatty
liver).
17

18. CHOLESTEROL
• One of the important non fatty acid lipid that
is grouped with steroids.
• A very hydrophobic compound that consists
of four fused hydrocarbon rings (steroid
nucleus), and eight carbon branched
hydrocarbon chain attached at C-17 of the D
ring
18

19. CHOLESTEROL
19

20. CHOLESTEROL
Cholesterol is important in many ways:
• Steroids with diverse physiological functions are
derived from cholesterol. Eg: Vitamin D, Bile acids
• For the synthesis of bile salts that are important in
lipid digestion and absorption.
• For the synthesis of steroid hormones like the sex
hormones estrogen and progesterone.
20

21. Lipid metabolism: Digestion and
absorption of lipid
• The dietary lipids consists primarily of
triacylglycerol, cholesterol, cholesteryl esters,
phospholipids, and unesterified (“free”) fatty
acids.
• The digestion of dietary lipids begins in the
stomach and continues in the small intestine.
• The hydrophobic nature of lipids requires that
the dietary lipids—particularly those that contain
long-chain length fatty acids (LCFA)—be
emulsified for efficient degradation.
21

22. Digestion and absorption of lipid
• Cholesteryl esters (CE), phospholipids (PL),
and TAG containing LCFAs are degraded in the
small intestine by enzymes secreted by the
pancreas.
• The most important enzymes are pancreatic
lipase, phospholipase A2, and cholesteryl
esterase.
22

23. Digestion and absorption of lipid
• The dietary lipids are emulsified in the small
intestine using peristaltic action, and bile salts,
which serve as a detergent.
• The products resulting from enzymatic
degradation of dietary lipid are 2-
monoacylglycerol, unesterified cholesterol,
and free fatty acids (plus some fragments
remaining from PL digestion).
23

24. De Novo Synthesis of Fatty Acids
• In adult humans, fatty acid synthesis occurs in
cytosol
• Major steps include
-Production of cytosolic acetyl CoA
-Carboxylation of acetyl CoA to form malonyl CoA
-Fatty acid synthase: a multifunctional enzyme in
eukaryotes
-Major sources of the NADPH required for fatty acid
synthesis
-Further elongation of fatty acid chains
24

25. Fatty Acid and Triacylglycerol Metabolism
• More than ninety percent of plasma fatty acids are
found in in the form of fatty acid esters
• fatty acid esters inculde triacyglycerol, cholesteryl
esters, and phospholipids
• Triacylglycerols have the highest energy content
(from complete oxidation over 9kcal/g of fat)
• Provide more than half the energy need of some
organs like brain, liver, heart and resting skeletal
muscle.
25

26. Mobilization of Fatty Acids from
Adipocytes (lipolysis)
• Lipases hydrolyze the triacylglycerols at position 1 or
3 to produce diacylglycerols (DAG) and fatty acid
-the rate limiting step in the hydrolysis.
• The diacylglycerol lipases hydrolyze the DAG to
monoacylglycerols (MAG) and fatty acid.
• Finally MAG lipases hydrolyze MAG to fatty acid and
glycerol.
• The fatty acids then enter cells, activated to their
CoA derivatives and are oxidized for energy
26

27. Mobilization of Fatty Acids from
Adipocytes
• The glycerol produced cannot be metabolized by
adipocytes because they lack glycerol kinase.
• Glycerol is transported through blood, taken up by liver
and phosphorylated.
• The resulting glycerol phosphate can be used to form
TAG in the liver or oxidized to dihydroxyacetone
phosphate (DHAP),
• DHAP is isomerised to glyceraldehyde-3-phosphate, an
intermediate of both glycolysis and gluconeogenesis.
• Therefore, the glycerol is either converted to glucose
(gluconeogenesis) or to pyruvate (glycolysis).
27

28. Transport of Fatty Acids to the
Mitochondria
• The major pathway for catabolism of saturated fatty
acids is a mitochondrial pathway called β-oxidation
• In order to undergo β-oxidation, the fatty acids must
enter the mitochondria.
• The fatty acids must first be activated or primed by
reaction with Coenzyme A at the expense of ATP.
• The reaction is catalyzed by long chain fatty acyl CoA
synthetase (thiokinase) in the cytosol.
28

29. Transport of Fatty Acids to the
Mitochondria
1. An acyl group is transferred from the cytosolic CoA
to carnitine by carnitine palmitoyltransferase I (CPT-
I)
2. The acyl carnitine is transported into the
mitochondrion in exchange for free carnitine
• The reaction catalyzes the transfer of the acyl group
from carnitine to coenzyme A in the mitochondrial
matrix, thus generating free carnitine
29

30. Transport of Fatty Acids to the
Mitochondria: Carnitine shuttle
30

31. β-oxidation of Fatty Acids
• Definition:
The successive oxidative removal of two carbons in
the form of acetyl–CoA beginning from the carboxyl
end.
• It requires a set of enzymes.
• It takes place in the mitochondrial matrix
31

32. β-oxidation of Fatty Acids
1. Converts Fatty acyl CoA to enoyl CoA
-Acyl CoA dehydrogenase catalyzes the reaction
2. Converts enoyl CoA to 3-hydroxy acyl CoA.
- Enoyl CoA Hydratase catalyzes the reaction
3. Converts 3-hydroxy acyl CoA to 3-keto acyl CoA.
- Hydroxy acyl CoA dehydrogenase catalyzes the
reaction
4. Further convertion to Fatty acyl CoA and acetyl CoA
- Thiolase catalyzes the reaction
32

33. β-oxidation of Fatty Acids
*Acetyl CoA is a positive allosteric effector of
pyruvate carboxylase, thus linking fatty acid
oxidation and gluconeogenesis.
*The cycle is repeated for saturated fatty acids
of even-numbered carbon chains
33

34. β-oxidation of Fatty Acids
34

35. β-oxidation of Fatty Acids
• The FADH2 and NADH +H+ join the electron
transport chain as high energy electron
carriers.
• The latter donates its reducing equivalents
(hydrogens) to NADH dehydrogenase to
produce 3ATP per pair of electrons and the
former produces only 2ATPS.
35

36. β-oxidation of Fatty Acids
• Complete oxidation of fatty acid can be divided in to
two stages.
A. Formation of acetyl CoA.
B. Oxidation of acetyl CoA to CO2 and water via TCA
cycle.
36

37. Fatty Acids oxidation
The fates of acetyl-CoA formed by β-oxidation of
fatty acids are:
1. Oxidation to CO2 and H2O by citric acid cycle
2. Synthesis of lipids like cholesterol, fatty acids
and other steroids
3. Formation of ketone bodies in the liver
37

38. The metabolism of Ketone Bodies
• Increases of acetyl CoA from β-oxidation in
excess of that required for entry into the
citric acid cycle, It undergoes ketogenesis in
the mitochondria of liver (ketone body
synthesis).
• Ketone bodies are important sources of
energy for peripheral tissues
• The synthesis of ketone bodies takes place
during severe starvation or severe diabetes
mellitus.
38

39. Cont…
• During such conditions, the body totally
depends on the metabolism of stored
triacylglycerols to fulfill its energy demand.
• In diabetes, high fatty acid degradation
produces excessive amounts of acetyl CoA.
• It also depletes the NAD+ pool and increases
the NADPH+ pool, which slows the TCA cycle.
• This forces the excess acetyl CoA into the
ketone body pathway.

40. Cont…
• When the rate of formation of ketone bodies is
greater than the rate of their use, levels begin to
rise.
-in the blood, ketonemia and
-in the urine, ketonuria
• These conditions are seen most often in cases of
uncontrolled, type I (insulin dependent) diabetes
mellitus.
• A frequent symptom of diabetic ketoacidocis is a
fruity odor on the breath which result from
increased production of acetone

41. Mechanism of diabetic ketoacidosis
seen in type 1 diabetes
41

42. Cholesterol Biosynthesis
• The major sterol in animal tissue
• Cholesterol synthesis occurs in cytoplasm with
enzymes both in cytosol and endoplasmic
reticulum.
• Acetyl-CoAs generated from the break down of
carbohydrates, fats and amino acids act as
precursors of cholesterol.

43. Cont…
• The synthesis follows the following major
steps:
- Acetyl CoA is converted to HMG CoA.
- HMG CoA is reduced to Mevalonate by a
reductase (rate limiting step in the synthesis
of cholesterol)
-Mevalonate undergoes Phosphorylation, in
the presence of 3 ATPs and various kinases.
-The product is 5 pyrophosphomevalonate.

44. Cont…
• The squalene undergo cyclization to generate
first sterol, lanosterol.
• Formation of cholesterol from lanosterol
occurs after several steps.

45. Catabolism of Cholesterol
• Humans lack enzyme system which can break steroid
nucleus of cholesterol. it is converted to bile acids
and bile salts which are excreted in feces
• Bile acids before leaving liver, conjugated to a
molecule of either glycine or taurine to form bile
salts
• cholesterol is secreted to bile which transports it to
the intestine for elimination .
• Bile salts secreted into the intestine are efficiently
reabsorbed and reused (Enterohepatic circulation)
45

46. Steroid Hormones
• Cholesterol is the precursor of all classes of
steroid hormones:
-glucocorticoids (Eg. cortisol),
-mineralocorticoids (Eg.aldosterone), and
-sex hormones (Eg. androgens, estrogens, and
progestins).
46

47. lipoproteins
• Is spherical macromolecular complexes of lipids and
specific proteins (apoproteins or apolipoproteins)
• The lipoprotein particles include:
1. chylomicrons
2. very-low density lipoproteins (VLDL)
3. low-density lipoproteins (LDL), and
4. high-density lipoproteins (HDL)
47

48. Chylomicrons
• These are derived from intestinal absorption of
triacylglycerols and other lipids
• Have a very short lifespan
• They have the least density and richly consist TAG.
• Transport dietary triacylglycerols and cholesterol
from the intestine to the liver for metabolism.
VLDL (very low density lipoproteins):
• synthesized in the liver
• Transport triacylglycerols from the liver to
extrahepatic tissues.
48

49. LDL (Low density lipoproteins):
• Produced from the final stage in the
catabolism of VLDL.
• Transport cholesterol synthesized in the liver
to peripheral tissues.
• Approximately 30% of the LDL is degraded in
extra hepatic tissues, rest is degraded in liver.
49

50. HDL (High Density Lipoproteins)
• Has the highest density since it contains more protein
and cholesterol than triacylglycerols.
• Transports excess cholesterol from peripheral tissues
to the liver for degradation and removal.
• Therefore, HDL cholesterol is good cholesterol but LDL
cholesterol is called bad cholesterol.
• High concentration of circulating VLDL,LDL are
indicative of possible atherosclerosis.
50

51. Atherosclerosis
• It is an abnormality associated with cholesterol
metabolism.
• Blood vessel narrowing due to deposition of
cholesterolester
• However, genetic factors are also involved in the
development of this disease.
• In this condition, initially cholesterol esters
particularly cholesterol oleates of arterial smooth
muscle cells deposits in arterial intima.
51

52. Atherosclerosis
• Plaque in arteries promotes clot formation
• If clot formation occurs in coronary artery, the
blood and O2 supply to cardiac muscle
diminishes.
• This manifest as myocardial infarction or stroke
because anoxia causes necrosis of cardiac tissue.
• Atherosclerosis may develop as secondary
complication of diseases like diabetes,
hypothyroidism, lipid nephrosis and other type of
dyslipoproteinemias.
52

53. Fatty liver
53
• For a variety of reasons, lipid mainly as tri-
acylglycerol(TAG) can accumulate in the liver.
• Extensive accumulation is regarded as a
pathologic condition.
• When accumulation of lipid in the liver
becomes chronic, fibrotic changes occur in the
cells that progress to cirrhosis and impaired
liver function.