2. Lipid Chemistry Prostaglandins & Eicosonids

Lipids and their chemistry therapeutic functions of prostaglandins and eicosanoids

1. LIPIDS
(LECTURE 2)
LIPID CHEMISTRY-II
Dr Gurjinder Singh
GMC DODA

2. COMPETENCY BI 4.1
Describe and discuss main classes of lipids
relevant to human system and their major
functions.
Competency BI 4.6
Describe the therapeutic uses of prostaglandins
and inhibitors of eicosanoid synthesis.

3. SPECIFIC LEARNING OBJECTIVES
Explain the structure and functions of
lipoproteins.
Define and classify fatty acids.
Explain essential fatty acids with its functions
and deficiency manifestations
Describe structure and functions of cholesterol
Define eicosanoids
Describe the therapeutic uses of prostaglandins
Describe the therapeutic uses of inhibitors of
eicosanoid synthesis

4. LIPOPROTEINS
They are the molecular complexes of lipids with
proteins.
They are the transport vehicle for lipids in
circulation.
They are of five types
1.Chylomicrons
2.Very low density lipoproteins
3.Low density lipoproteins
4. High density lipoproteins
5. Free fatty acid-albumin complexes

5. Polar lipids
(phospholipids)
Nonpolar lipids
(cholesterol and its esters
and triacylglycerols)
Structure of a plasma lipoprotein complex
Polar apolipoproteins

6. STRUCTURE

7. FUNCTIONS OF LIPOPROTEINS
Chylomicrons : Transport exogenous TAG to
various tissues.
VLDL: Transport endogenous TAG to various
tissues.
LDL: Transport cholesterol from liver to other
extrahepatic tissues: Lethally Dangerous
Lipoprotein.
HDL: Transport cholesterol from extrahepatic
tissues to liver. (Reverse cholesterol transport):
Highly desirable Lipoprotein.

8. FATTY ACIDS
Simplest form of lipids.
Carboxylic acids with hydrocarbon side chains.
Represented by chemical formula R-COOH
Here R stands for hydrocarbon chain.
The hydrocarbon chain accounts for the non-
polar nature of fatty acids.

9. FATTY ACIDS- OCCURRENCE
FA are mainly found in esterified form.
They may present in unesterified form and called
as free fatty acids.
FFA are transported in circulation, binding to
albumin. (FFA-albumin)
Animal origin are much simpler
Plants origin often contain groups such as
epoxy, keto, hydroxy and cyclopentano rings

10. CLASSIFICATION OF FATTY
ACIDS:
1.Even and Odd carbon FA
2.Saturated and Unsaturated FA
3.Short, Medium & Long chain FA
4.Straight & Branched Chain FA
5.Hydroxy FA
6.Cyclic FA

11. 1. EVEN AND ODD CARBON FA
FA in natural lipids are even carbons usually
14C – 20C e.g. palmitic acid (16 C), stearic acid
(18C).
As Biosynthesis of FA (FAS) mainly occurs with
sequential addition of 2 carbon atoms.
Odd chain fatty acids e.g. propionic acid (3C) and
valeric acid (5C) .

12. 2. SATURATED AND
UNSATURATED FA
According to the degree of saturation.
1. Saturated FA (SFA): have no double bonds
between carbon atoms. (ends with suffix –
“anoic”)
2. Unsaturated FA (UFA): possess double bonds in
structure (ends with suffix – “enoic” )
Classified based on number of double bonds.
A. Monounsaturated Fatty acids (MUFA): contain
one double bond.
B. Polyunsaturated Fatty acids (PUFA): contain
two or more double bonds.

13. SATURATED FA

14. UNSATURATED FA
The double bonds in polyunsaturated fatty acids
of both animals and plant origin are usually
three carbon atoms apart.

15. OMEGA SERIES FATTY ACIDS
Naturally occurring unsaturated fatty acids belong
to ω-9, ω-6 and ω-3 series.
ω-9 : Oleic acid (C:18:1:ω-9)
ω-6 : Linoleic acid (C:18:2:ω-6)
Arachidonic acid (C:20:4:ω-6)
ω-3 : Linolenic acid(C:18:3:ω-3)

16. 3. SHORT, MEDIUM & LONG
CHAIN FA
Depending on the length of carbon chains.
1. Short chain FA: 2 to 6 carbons
2. Medium chain FA: 8 to14 carbons
3. Long chain: 16 to 24 carbons
4. Very long chain: More than 24 carbons

17. 4 . STRAIGHT & BRANCHED CHAIN
FA
Fatty acids are usually unbranched.
Some FA of plant origin (phytanic acid) contains
several methyl groups as branching points.
Refsum’s disease: Accumulation of Phytanic acid
Examples: Isovaleric acid, Isobutyric acid
Metabolic intermediate

18. 5. Hydroxy FA
Beta-hydroxy butyric acid (Ketone body)
Cerebronic acid, Recinoleic acid
6. Cyclic FA
Chaulmoogric acid found in chaulmoogra oil
contains cyclopentenyl ring: Used in leprosy
treatment.

19. ESSENTIAL FATTY ACIDS

The fatty acids that are required by humans, but
are not synthesised in the body and hence need
to be supplied in the diet.
1. Linoleic acid (18: 2; 9, 12)
2. Linolenic acid (18: 3; 9, 12, 15)

Arachidonic acid (20: 4; 5, 8, 11, 14) is considered
semi essential since it can be synthesised from
linoleic acid (note that both belong to ω6 series).

20. ESSENTIAL FATTY ACIDS
Only linoleic acid and linolenic acid are essential
because humans lack the enzymes that can
introduce double bonds beyond carbon no. 9.
Vegetable oils are the richest source of fatty
acids.

Oils rich in SFA: Palm oil, coconut oil, ghee.

Oils rich in MUFA: Groundnut oil, gingily oil,
mustard oil, sesame oil.

Oils rich in PUFA: Sunflower oil, cotton seed
oil, safflower oil, rice bran oil, soyabean oil,
linseed oil, corn oil.

21. FUNCTIONS OF EFA
Integral components of membrane structure.
Concentrated source of energy
Formation of lipoproteins: Transport of
cholesterol
Prevention of fatty liver (lipotropic factors)
Formation of Eicosanoids.
Bioavailability of Fat soluble vitamins.
Consumption of EFA (ω3 series : Linolenic acid)
lowers the risk of cardiovascular disease.
(Antiatherogenic effect)

22. FUNCTIONS OF EFA
Development of Retina and Brain
 Docosahexaenoic acid (DHA: ω-3), synthesized
from linolenic acid is needed for development of
the brain and retina during the neonatal period.
Skin protector
 EFA helps to make the skin impermeable to
water

23. DEFICIENCY OF EFA
Rare in humans.
In infants receiving formula diet and patients on
IV nutrition low in EFA.
Phrynoderma or toad skin or Scaly dermatitis
Characterized by presence of horny eruption on
the posterior and lateral parts of limbs ,back and
buttocks.

24. PHRYNODERMA OR TOAD SKIN OR
SCALY DERMATITIS

25. CHOLESTEROL
Animal sterol
Body contents:130-150g (2g/kg body wt.)
Sources:1)Dietary- 0.3 g/D milk, egg yolk
2)Synthesized endogenously-1g/D, all tissues

Liver 50%, Intestine(15%), Skin, Adrenal cortex.
Plasma: both free(30%) and esterified (70%) forms
Fecal excretion: major as bile salts
(0.5 g/D- 50% of total 1000 mg))

26. FUNCTIONS OF CHOLESTEROL
1.Insulating cover for the
transmission of electrical
impulses in nervous system.
2.Role in membrane structure
and function.
3.Essential ingredient in
structure of lipoproteins.
4.Synthesis of bile acids , Steroid
hormones (sex hormones,
cortical hormones) , vit D3.

27. SERUM CHOLESTEROL &
PRINCIPLE
Desirable : 140 – 200 mg/dL
High normal : 201- 239 mg/dL
Abnormal : 240 & above.
Cholesterol Oxidase-Peroxidase Method: (CHOD-
POD)

28. HYPERCHOLESTEROLEMIA
Increase in plasma cholesterol >200 mg/dl
Observed in-
1.Diabetes mellitus.
2.Hypothyoroidism & hypopituitarism
3.Obstructive jaundice
4.Nephrotic syndrome
5.Xanthomatosis
6. Idiopathic
Hypercholesterolemia is associated with
atherosclerosis & coronary heart disease.

29. CONTROL OF
HYPERCHOLESTEROLEMIA
1. Consumption of PUFA.
2. Avoid high carbohydrate & rich cholesterol
diet
3. Plant sterols
4. Dietary fiber
5. Lifestyle modification
6. Drugs: Statins, Fibrates
7. Moderate alcohol consumption : Red wine

30. HYPOCHOLESTEROLEMIA
1. Thyrotoxicosis
2. Pernicious anemia
3. Malabsorption syndrome
4. Hemolytic jaundice
5. Wasting diseases

31. EICOSANOIDS
Definition: Group of biologically active molecules
synthesized from eicosaenoic acids (C20 PUFA). Act as
local hormones.
Synthesized from Arachidonic acid.
eikosi = Twenty
Prostaglandins (PG)
Prostacyclins (PI)
Thromboxanes (TX)
Leukotrienes (LT)
Lipoxins (LX)

33. BIOLOGICAL ROLE AND
THERAPEUTIC APPLICATIONS
1.Inflammation:
Tissue response to injury is characterized by 5
cardinal signs- dolour (pain), calor (raised temp.),
rubor (redness), tumor (swelling) and loss of function.
Eicosanoids PGE1 & PGE2 are the natural mediators
of inflammation.
Corticosteroids and NSAID- T/t inflammatory
disorders, eg arthritis. (Inhibit PG Synthesis)
2.Regulation of blood pressure:
Vasodilators;↓ BP, T/t of hypertension.

34. 3. Effects on platelet aggregation:
Thromboxanes cause platelet aggregation forming blood
clot, Prostacyclins inhibits platelet aggregations.
4. Effects on reproduction:
Prostaglandins PGE2 & PGF2 are used in medical
termination of pregnancy, induction of labour and
arresting postpartum hemorrhage.
5. Effect on GIT:
PGE ↑es intestinal motility and inhibits gastric acid
secretion, T/t – gastric ulcers.

35. 6. Effects on respiratory system:
PGE-bronchodilator, PGF-
bronchoconstrictor. PGE- T/t bronchial asthma.
7. Effects on metabolism:
PG influences metabolic reactions through
mediation of cAMP. PGE ↓es lipolysis, ↑es
glycogenesis and mobilization of calcium from
bone.
8. Effects on excretory system:
↑es GFR and promotes urine output.

36. 9. Leukotrienes:
Integral component of SRS-A (slow reacting substance
of anaphylaxis)
Overproduction causes asthmatic attacks.

37. SUMMARY
Explain the structure and functions of
lipoproteins.
Define and classify fatty acids.
Explain essential fatty acids with its functions
and deficiency manifestations
Describe structure and functions of cholesterol
Define eicosanoids
Describe the therapeutic uses of prostaglandins
Describe the therapeutic uses of inhibitors of
eicosanoid synthesis

38. BIBLIOGRAPHY
1.Harper’s Illustrated Biochemistry, 8th Edi.
 Murray & Bender
2. Biochemistry, 4th edition.
 Satyanarayan, & Chakraworthy
3. Text Book of Biochemistry,6th edi.
 Vasudevan & Sreekumari S
4.Lippincott’s Biochemistry, 5th edi.
 Harvey & Ferrier

39. Thank you