1. LIPIDS OF PHYSIOLOGICAL SIGNIFICANCE
&
ITS ROLE IN HEALTH AND DISEASES
Presented by,
Shruti Sharma
(D.Phil Scholar)

2. Why lipids are important-
Lipids are important to the body because;-
1) Important constituent of the cell membranes.
2) Helps in the absorption of fat soluble
vitamins.
3) Maintains membrane fluidity.
4) Acts as a thermal insulator and cellular
metabolic regulator.
5) Hormone synthesis.
6) Organ padding.
•

3. Major lipids of physiological significance;-
 Fatty acids ;- basic units of fat composed of chains of
carbon atoms with an acid group at one end and hydrogen
atoms attached all along their length.
 Present as either esterified or unesterified form in fats and oils.

4. Classification of fatty acids;-
Fatty acids
Saturated FA Unsaturated FA

5. Saturated fatty acids;-
•
Saturated fatty contains no double bonds (having no points of
unsaturation).
Saturated fats- considered as harmful. It increases total
cholesterol level and TGs level.
Hypercholestrolemic SFAs are-Myristic acid & Lauric acid.

6. Unsaturated fatty acids;-
Unsaturated fatty acid: a fatty acid with one or more points of
unsaturation. Unsaturated fats are found in foods from both plant
and animal sources. Unsaturated fatty acids are further divided
into monounsaturated fatty acids and polyunsaturated fatty acids.

7. Divisions of unsaturated fatty acids;-
Unsaturated
Fatty acids
MUFA PUFA Eicosanoids

8. Monounsaturated fatty acids;-
 Monounsaturated fatty acid: a fatty acid containing
one point of unsaturation, found mostly in vegetable oils
such as olive, canola, and peanut.
 They are considered as beneficial for human health.
MUFA
Cis FA Trans FA

9. Cis- unsaturated fatty acids;-
 In cis bonds, the two pieces of the carbon chain on either side
of the double bond are either both “up” or both “down,” such
that both are on the same side of the molecule.
 Significance –
 Decreases total cholesterol and TGs level.
 Increases HDL level.

10. Trans unsaturated fatty acids;-
 Trans fatty acids are produced by hydrogenation process.
 Hydrogen atoms are on the opposite sides of the molecule.
 Eg.cis-oleic acid trans-elaidic acid
PHYSIOLOGICAL EFFECTS OF
TRANS FATTY ACIDS
-
SERUM LIPIDS
-SYSTEMIC INFLAMMATION
-ENDOTHELIAL-CELL FUNCTION

11. Physiological effects of trans fatty acids continued…
SERUM LIPIDS—
>raises levels of low-density lipoprotein (LDL) cholesterol
reduces levels of high-density lipoprotein (HDL) cholesterol
>increases the ratio of total cholesterol to HDL cholesterol, a
powerful predictor of the risk of CHD
>increase the blood levels of triglycerides , of Lp(a)
lipoprotein, and reduce the particle size of LDL cholesterol:
further raise the risk of CHD.
>trans fatty acids have markedly adverse effects on serum
lipids

12. Physiological effects of trans fatty acids continued…
Systemic inflammation—
inflammation: an independent risk factor for atherosclerosis,
sudden death from cardiac causes, diabetes, and heart failure
the inflammatory effects of trans fats may account in part for
their effects on cardiovascular health
For example,
the difference in C-reactive protein levels ;
2.1 percent vs 0.9 percent intake: an increase in
cardiovascular risk of approximately 30 percent.

13. Physiological effects of trans fatty acids continued…
ENDOTHELIAL-CELL FUNCTION--
increased levels of several markers of endothelial
dysfunction:
for eg;-
soluble intercellular adhesion molecule, soluble vascular-
cell adhesion molecule, and E-selectin

14. Polyunsaturated fatty acids;-
Polyunsaturated fatty acids (sometimes abbreviated PUFA)
are those fatty acids where unsaturation occur more than two
points, found in nuts and vegetable oils such as safflower,
sunflower, and soybean, and in fatty fish.
They possess protective role on human health.considered as
beneficial for consumpmtion.

15. PUFA continued;-
 Increase esterification process of cholesterol & prevents its
absorption.
 By increasing the synthesis of eicosanoids.
 Acts as an anti platelet aggregating factor, so decreases the
chances of clot formation.
 Decreases the synthesis of the precursor of VLDL AND TGs.
 Increases clearance of LDL cholesterol.

16. 
Omega-3-fatty acids-
Benefits-
>Lower PGE2s level
>Anti-inflammatory
>Lower triglyceride and
cholesterol levels
>Benefits vision and
>brain function
>Decrease Skin
>inflammation
>Inhibit platelet adhesion
>Increase insulin
sensitivity

17. Omega-6 fatty acids-
Linoleic fatty acid
Arachidonic acid
Benefits-
Platelet aggregation,
cardiovascular
diseases, and
inflammation.
Reduce the symptoms
of eczema and
psoriasis.
Clear up different
types of acne.

18. Eicosanoids;-
 These compounds are derived from long chain polyenoic fatty
acids (20-carbon).
 Examples of eicosanoids;- They have roles in:
Inflammation
 Prostaglandins. Fever
 Prostacyclines, Regulation of blood pressure
Blood viscosity
 Thromboxanes
Male fertility
 Leukotrienes Female conception
 lipoxins Muscle cotraction
Blood clotting
Tissue growth
Regulation of sleep/wake cycle
Bronchocostriction
Asthma.

19. Triglycerides;-
Structure
Glycerol + 3 fatty acids
Functions
Energy source--9 kcals per gram
Form of stored energy in adipose
tissue.
Insulation and protection
Carrier of fat-soluble vitamins
Sensory properties in food

20. Phospholipids;- main lipid constituent of cell
membrane.
Structure
Glycerol + 2 fatty acids + phosphate group
also considered as derivative of ‘phosphatidic acid’.
Functions
Main lipid constituent of cell membranes
Lipid transport as part of lipoproteins
Emulsifiers
Cell signalling process.
phospholipids
Phos.choline phos.inositol cardiolipin lysophospholipid plasmalogens sphingomy.

21. Sterols;-
Steroids are the compounds contains
cyclic steroid nucleus namely cyclo
pentanophenanthrene ring.
Cholesterol-
best known steroid because of its
association with atherosclerosis and
heart diseases.
Contains same steroid nucleus.
Exclusively present in animals
. Functions;-
--Bile acids
– Sex hormones
– Adrenal hormones
– Vitamin D
--Cardiac glycosides

22. Glycolipids;-
 --widely distributed in the body
 Fatty acids + sphingosine +carbohydrate
 Also k/a glycosphingolipids.
 Present in cell membrane and nervous tissues.
 It contributes to cell surface carbohydrate
 Other glycolipids are;-
 Cerebrosides- simplest form of glycolipids.contains ceramides.
 eg. Galactosylcerebrosides
 glucosylcerebrosides
 Gangliosides – predominantly found in ganglions.Complex
glycolipids

23. Lipoproteins;-
Lipoproteins are th
macromolecular complex of
lipids and proteins.
Transportation of lipids in the
blood.
Structure of lipoproteins;-
Hydrophobic lipids (TG, CE) in
core;
Hydrophilic lipids (UC, PL) on
surface

24. Classes of lipoproteins;-
Chylomicrons, LDL HDL
VLDL,
> 30 nm 20–22 nm 9–15 nm
D<1.006 g/ml D=1.019-1.063g/ml D=1.063-1.21 g/ml
Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000;
149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994

25.  Apolipoproteins—
 Apo AI (liver, small intestine)
 Structural; activator of lecithin:cholesterol acyltransferase
(LCAT)
 Apo AII (liver)
 Structural; inhibitor of hepatic lipase; component of ligand
for HDL binding
 Apo A-IV (small intestine)
 Activator of LCAT; modulator of lipoprotein lipase (LPL)
 Apo A-V (liver)
 Direct functional role is unknown; regulates TG levels.

26.  Apoprotein continued…
 Apo B-100 (liver)
 Structural; synthesis of VLDL; ligand for LDL-receptor
 Apo B-48 (small intestine)
 Structural; synthesis of chylomicrons; derived from apo B-
100 mRNA following specific mRNA editing
 Apo E (liver, macrophages, brain)
 Ligand for apoE receptor; mobilization of cellular
cholesterol

27. Apoprotein continued…
 Apo C-I (liver)
 Activator of LCAT, inhibitor of hepatic TGRL uptake
 Apo C-II (liver)
 Activator of LPL, inhibitor of hepatic TGRL uptake
 Apo C-III (liver)
 Inhibitor of LPL, inhibitor of hepatic TGRL uptake

28. Chylomicrons;- TG rich.
Synthesized in
intestine.
Transports
endogenous TGs.
Hydrophobic Core
Triglyceride (93%)
Cholesteryl Esters
(1%)

29. VLDL;- rich in CE and TGs-
Surface
Monolayer
Phospholipids
(12%)
Free Cholesterol
(14%)
Protein (4%)
Hydrophobic Core
Triglyceride
(65%) Cholesteryl
Esters (8%)

30. LDL;- cholesterol rich.
Surface Monolayer
Phospholipids (25%)
Free Cholesterol
(15%)
Protein (22%)
Synthesized from
VLDL in blood
circulation.
Transports cholesterol
from liver and delivers
to other tissues.

31. High density lipoprotein-
Surface Monolayer
Phospholipids (25%)
Free Cholesterol
(7%)
Protein (45%)
Promotes re-
esterification process
of cholesterol.

32. HDL Subpopulations
Particle Shape Apolipoprotein Composition
Discoidal
Spherical
A-I HDL A-I/A-II A-II HDL
HDL
Particle Size Lipid Composition
TG, CE, and PL
HDL2b HDL2a HDL3a HDL3b HDL3c
Rye et al. Atherosclerosis 1999;145:227-238.

33.  The Effects of Various Types of Fat on Blood Lipid
Levels
 • Saturated Fat
 – Increases total cholesterol
 – Increases LDL-cholesterol
 • Polyunsaturated Fat
 – Decreases total cholesterol
 – Decreases LDL-cholesterol
 – Decreases HDL-cholesterol
 • Monounsaturated Fat
 – Decreases total cholesterol
 – Decreases LDL-cholesterol
 – Increases HDL-cholesterol

34.  Omega-3 Fat
 – Decreases total cholesterol
 – Decreases LDL-cholesterol
 – Increases HDL-cholesterol
 – Decreases serum triglycerides
 • Trans Fat
 – Increases total cholesterol
 – Increases LDL-cholesterol

35. Role of lipids in health and diseases – omega-3 FAs.
Docosahexanoic acid and
brain development-
It is becoming increasingly evident that long-chain PUFA
from the (n-3) family appear to be neuroprotective and
that long-chain PUFA from the (n-6family) may also have
unique properties in affecting neurobiology.
•It is found in very high concentrations in the cell
membranes of the retina and cerebral cortex.
•Whelan et al,(2008) focused on docosahexaenoic
acid (DHA),4 a PUFA that is preferentially
deposited in brain phospholipids and has been
linked to dementia, Parkinson disease, Alzheimer
disease (AD),cognitive function, mental stability,
suicide, depression, bipolar disorders, impulsivity,
aggression, etc. (3–10). The content of DHA in the
brain is 12–15%, 10- to 20-fold higher than any
other (n-3) PUFA.

36. Arachidonic acid and the brain--
One of the most important changes in this field is the link between arachidonic acid
(AA) content and brain function. The level of AA in the brain is comparable to that
of DHA. At 8–11% of the fatty acid phospholipids, it is severalfold higher
than any other (n-6) PUFA (by comparison, linoleic acid content is ;1%).
Connell et al,(2007) demonstrated that dietary AA appears to influence plasticity
and preserve hippocampal membrane fluidity and may provide some protection to
oxidative stress via the activation of peroxisomal proliferatoractivated
receptor-g (17). Furthermore, it has been shown that AA, as well as DHA, activates
syntaxin-3, a critical factor in the growth and regeneration of neurons.

37. Prevention of cancer;-
Marine-derived fatty acids have been found to inhibit
proliferation and promote apoptosis in breast, prostate, and colon
cancer cell lines cultured outside the body
Studies in animal models of cancer also indicate that increased
intake of EPA and DHA decreases the occurrence and
progression of mammary, prostate, and intestinal tumors

38. Lipids related disorders;-
 lipid disorders
Common disorders Uncommon disorders
Hypercholetrolemia Metabolic disorders of cerebrosides.
Hypertriglyceridemia Lipidoses / lipid storage diseases
Hyperlipoproteinemia Multiple sclerosis.
ketosis Infant respiratory distress syndrome
CVD Xanthomatosis.
Fatty liver Retinitis pigmentosa.
Obesity Phrynoderma / Toad skin.
cancer Disorders of EFAs deficiency.
Zwellweger’s disease.

39.  ATHEROSCLEROSIS:
 As LDL particles penetrate the walls of the arteries, they
become oxidized-LDL and next are scavenged by the body’s
white blood cells.
 • These foam cells are then deposited into the
lining of the artery wall.
 • This process, known as atherosclerosis, causes
plaque deposits to enlarge, artery walls to lose
elasticity, and the passage through the artery to narrow.

40. Diagrammatic representation of the disease (atherosclerosis)-

41. Metabolic disorders of cerebrosides
diseases Enzyme Lipid symptoms
deficiency accumulating
Tay –sachs hexosamini gangliosides Mentalretardation,blindness,muscu
disease dase lar weakness.
Fabry;’s A- galactosylceramide Skin rashes,kidney failure
disease galactosidase.
Krabbe’s B- galactosylceramid Mental retardation,complete loss
disease galactosidas e of myelin sheath.
e
Gaucher’s B- glucosylceramide Enlarged liver and spleen, eroison
disease glucosidase of long bones ,mental retardation
Niemann- sphingomye sphingomyelin Enlarged liver and spleen
pick disease linase
Farber’s ceramidase ceramide Dermatitis,skeletal
disease deformation,hoarseness.
Ref- Harper’s biochemistry

42. Lipoprotein disorders;- Hyperlipoproteinemias-
Hy. Metabolic defect Increased plasma Risk of athersclerosis
Lipo.types lipid most
l Deficiency of chylomicrons increase
lipoproteinlipase
lla Deficiency of cholesterol Very high
LDLreceptors
llb Overproduction of TGs and cholesterol high
apo-b
lll Abnormality in apo -e TGs and cholesterol high
lv Overproduction of TGs May/may not increase
TGs
v --do-- Chylomicron and --do--
VLDL
Ref- Harper’s biochemistry

43. Infant repiratory distress syndrome-
Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin.
It prevents collapsing of the alveoli and also decreases the surface tension .
Deficiency is common in young infants.
Xanthomatosis;-
Deposition of yellow-orange colours lipids occurs in the liver ,spleen and flat
bones.
Usually related with severe hypercholesterolemia and hyperlipidemia.
Phrynoderma or Toad skin;-
Caused due to the deficiency of essential fatty acids.
Horny eruptions occurs on posterior and lateral limbs.poor wound healing.
Multiple sclerosis;-
It is a demyelinating condition. loss of both phospholipids and sphingolipids
occurs from white matter. Neurodegeneration is common.

44. Defects in the metabolism of essential fatty acids -
Cystic fibrosis,Acrodermatitis enterohepatica,Hepato renal syndrome, Crohn’s
disease,Cirrhosis, Alcoholism, Reye's syndrome etc.
Zwellweger’s disease;-
Rare disorder.
occurs due to the accumulation of long chain polyenoic fatty acids in the brain.
Causes loss of functions and neural degeneration .
Dicarboxylic aciduria-
It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of
mitochondrial acyl coA dehydrogenase enzyme.

45. Common Atherogenic dyslipidemias
)
􀂃 polygenic inheritance
– dietary component
– secondarily enhanced by
insulin resistance (see
further why)
􀂃 prognosis of combined
hyperlipidemia is worse
than that of
hypercholesterolemia
􀂃 main features
– impaired clearance of TAG
by LPL (􀂃 insulin) from
chylomicrons → increased
TAG and increased delivery
of TAG for liver
– increased production of
VLDL by liver (􀂃 insulin)
from TAG, FFA from adipose
tissue (􀂃 insulin) and
glucose (􀂃 insulin)
– therefore increased
conversion of VLDL to LDL
– low HDL

46. Fatty liver;-
When lipids accumulates excessively in liver, then it causes fatty
liver.
Dropletes of TGs are found in the entire hepatic cytoplasm,
this causes impairment in liver function.
Fatty liver may occur due to two main reason-
1) Increased synthesis of TGs.
2) Impairment in lipoprotein synthesis.
Fatty liver is associated with the fibrotic changes and cirrhosis.

47. Tangier Disease
>Autosomal codominant disorder due to mutations in
 both alleles of ABC1 gene
 • Extremely marked reduction in HDL-C and apoA-I
 • Markedly accelerated catabolism of apoA-I and
>apoA-II
 • Cholesterol accumulation:
 − Enlarged orange tonsils
 − Hepatosplenomegaly
 − Peripheral neuropathy

48. References--
1) Connell E, Darios F, Broersen K, Gatsby N, Peak-Chew SY, Rickman C,
Davletov B. Mechanism of arachidonic acid action on syntaxin- Munc18.
EMBO Rep. 2007;8:414–9
2) Granner,K. and Robert,K.(2006).Harper’s illustrated biochemistry .27th
edition.Tata McGraw Hills publication.
3)Satyanarayan,U. (2006).Biochemistry.3rd edition. Books and Allied (P)Ltd.
4) Whelan ,J.(2008).(n-6) and (n-3) Polyunsaturated Fatty Acids and the
Aging Brain: Food for Thought. Abstract J. Nutr. 138: 2521–2522.