This document discusses lipids and lipid metabolism. It begins by introducing Dr. Rakesh Sharma and providing his credentials. It then lists the key objectives of lipids, their major functions, chemistry including fatty acids and complex lipids. Examples of lipid storage diseases are provided including Gaucher's disease and Tay-Sachs disease. The major classes of lipids are defined including simple lipids, complex lipids, and derived lipids. Specific lipid subclasses such as phospholipids, sphingolipids, and glycolipids are described in detail. Common lipid-related diseases and examples of how lipid metabolism can cause diseases are summarized.

1. Dr Rakesh Sharma,
Professor
North DMC Medical College, Delhi
https://www.scribd.com/user/233583633/Professor-Rakesh-Sharma-
Biochemistry-Lectures
https://www.slideshare.net/RakeshSharma185

2. Objectives
 What are lipids? Know it.
 Major functions Know it.
 Chemistry: Fatty acids and complex lipids How function?
 Problem Based Learning: Show and Perform
1. 25 y lady presented liver, spleen large, bone pain,
glucosylceramide deposits- Dr Gaucher defined it.
2. 6 month baby presented regressed growth,cherry-red spot in
retina, GM2 ganglioside deposits. Dr Tay-Sach defined it.
3. 63 y man had gastric pain.Arachidonic acid-COX inhibitor gave
relief.
4. 45 y man had cardiac pain. Low aspirin COX inhibitor gave
relief.
5. 70 y man lipid Profile defines CVD/CHD diseases and relief.

3. LIPIDS
in (White Matter Brain)
in eyes
in RBC in Lungs
in Belly
in Heart,Bile,Brain
in CVS, Liver,
Intestine, Belly
in CVS and Heart
in CVS
in RBC
Phospholipids, Sulfolipids
in CVS,
Liver, Muscle
in Gonads
in Skin
Bile salts in Biliary system
GOOD LIPID PROFILE
Cholesterol 125-150 mg/dL
Triglycerides 125-250 mg/dL
HDL 35-65 mg/dL
NUTRITION RDA
Cholesterol 75 gm
Triglycerides 125 gm
PUFA in Oils 30 gm

4. Bio-Chemical Nature of Human Lipids
Hormones
Receptors
Enzymes
Carbohydrates
Amino Acids/Proteins
Lipids
Nucleic Acids
Vitamins/Minerals
Lecture 3
•Atoms (C,H,O,P,N,S,minerals)
Free Radical Diseases
•Molecules
Molecular Diseases
•Super-Assemblies
Structural Diseases
•Organelles, skeleton
Organelle Diseases
•Cells
Cell Diseases
•Tissues
Tissue Diseases
•Organs
Organ Diseases
•Systems
+
DRIVING ENERGY
LIVE HUMAN
BODY
Circulation, Distribution of Lipids Produce Bio-Energy Force in Different Organs
A + B  P1 P2

5. Major Nutrition Lipid Diseases
 Obesity (accumulated triglycerides)
 Diabetes mellitus, DKA (increased
LDL, VLDL, Ketone bodies)
 Atherosclerosis, Gall stone disease
(cholesterol, saturated fat deposits)
 Hypertension (high trans-fatty acids
and low polyunsaturated fatty acids)
 Cerebral stroke, cardiac arrest, fatty
liver, brain sphingolipids,
ganglioside and glycolipid diseases
(high glycolipid contents in organs)
 Infertility/reproductive diseases
(imbalanced steroid hormones)
 Fatty Liver, Hepatobiliary diseases
(Low bile salts, high cholesterol in bile)
 Rickets/Osteomalacia(steroid like
vitamin D deficiency)

6. Obesity,Fatty Liver,Gall Stones,Dyslipidemia
(Hypercholesterolemia, Hypertriglyceridemia, Prostaglandins)

7. What are lipids?
 Definition: Water insoluble, oily or greasy substances
that can be extracted with non-polar solvents, but not
with polar solvents
 Special features:
 Found in isolated membrane compartments
 In blood, lipids form complexes with proteins
 Lipids do not form polymers

8. Major functions in the body
 Fuel molecules
 Signal molecules
 Component of cell membranes
 Carrier of vitamins
 Thermal insulator
 Cushion and lubrication

9. Chemistry of lipids
 Glycerol
 Most lipids are composed of fatty acids
 Fatty acids:
 Long hydrocarbon chain with a polar carboxyl group at
the end (amphipathic molecule)
 Predominantly non-polar: greasy nature
 Naturally occurring fatty acids contain even no. of C
atoms (16/ 18 most abundant)

10. Nomenclature of Fatty acids
 Carbon position
 Based on:
 Chain length
 Saturated or unsaturated
 Double bonds: number and their positions
CH2OH
|
H-C-OH Glycerol
|
CH2OH
∆
ω

12. Saturated Fatty acids: anoic acids
 C16: Palmitic acid and C18: Stearic acid most abundant
 Humans body fat composition:
 50% - Oleic acid
 25% - Palmitic acid
 10% - Linoleic acid
 5% - Stearic acid
 Rest - Others

13. Unsaturated Fatty acids: enoic acids
 Geometric isomerism
 Cis: naturally occurring FA are cis
 Trans: Formed in body during metabolism
 Present in hydrogenated oils, Processed foods
 Fast food: High in TFA; Injurious to health
 Increases shelf life
 PUFA (POLYUNSATURATED FATTY ACIDS)

14. Trans fatty acids in diet cause atherosclerosis and coronary artery disease

15. Properties of lipids
 Solubility: length of HC chain
 Melting point:
 Unsaturation decreases melting point
 Increased chain length elevates melting point
 Soap formation:
 Form salts with alkalis (NaOH, KOH)
 Amphipathic molecules: emulsification
 Ca and Mg salts are insoluble: precipitate
 Saponification number: mgs of KOH reqd. for 1 gm of fat

16. Properties of lipids contd.
 Hydrogenation: Ni catalyst
 Halogenation: To assess unsaturation of the HC
chain
 Iodine number: gm of Iodine required to saturate 100gm
of lipid
 Higher the iodine number, higher the unsaturation
 Oxidation: Rancidity
 Spontaneous oxidation by atmospheric O2
 Acid number: mg of KOH to neutralize FA in 1gm of fat

17. Essential Fatty acids(EFA)
 Linoleic acid (18C:2)
 Linolenic acid (18C:3)
 Arachidonic acid (20C:4)
 Importance:
 Membrane components
 Synthesis of eicosanoids
 Lowers serum cholesterol and BP
 Vision: linoleic acid produces docosahexaenoic acid
 Structural elements
 EFA Deficiency causes Phrynoderma dry and scaly
dermatitis (skin lesions on limbs and back)

18. Classification
 Simple lipids
Compound lipids
 Phosphorylated
 Non-phosphorylated
 Derived lipids
 Complex lipids
with Examples
(Fats,Wax,Oils, Fatty Acids, Glycerols)
(Having Phosphatidic Acid, Amines)
(Phospholipids, Plasmalogens, Cardiolipin)
(Glycolipids, Sphingolipids-F+C+S)
(Ketone Bodies, Cholesterol, Steroids,Vitamin
D, Bile Salts,Prostaglandins,Hormones,
Eicosanoids, Thromboxanes, Leukotrienes)
(Sulfolipids,Aminolipids,Lipoproteins)

20. Simple lipids
 Esters of fatty acids with various alcohols.
 Fats: Triacylglycerol or Neutral fats
 Oils: fats in liquid state
 Waxes: Esters of fatty acids with higher molecular
weight monohydric alcohols.

21. Complex lipids
Esters of FA containing groups in addition to an alcohol and
a fatty acid.
 Phospholipids: having
phosphoric acid residue
 Glycerophospholipids:
glycerol
 Sphingophospholipids:
sphingosine.
 Glycolipids
(glycosphingolipids):
Fatty acid + sphingosine +
carbohydrate
• Other complex lipids:
Sulfolipids Aminolipids Lipoproteins

22. Phospholipids
 Glycerol + Fatty acid + nitrogenous bases
 Can be considered as derivatives of phosphatidic acid:
Phosphatidic acid + Amine  Phospholipids

23.  Phosphatidylcholine (Lecithin)
 Most abundant PL in cell membrane
 Body reserve of choline
 Neurotransmitter
 Store of labile methyl groups
 DiPalmitoyl lecithin: major constituent of surfactant
 Phosphatidylethanolamine (cephalin)
 Phosphatidylserine
 Apoptosis
 Phosphoinositol
 Secondary messenger
Phospholipids contd……

25.  Dipalmitoyl Lecithin: only in Lung alveoli (next slide)
• Stimulates air flow in lungs: surfactant in lung alveoli RDS
 Phosphatidylinositol 4,5-bisphosphate: cell membrane
 Stimulation by renal hormones cleave it into diacylglycerol and inositol
trisphosphate: Act as second messengers Renal Loss
 DiPhosphatidyl Glycerol (Cardiolipin): in Cardiac mitochondria
 Antiphospholipid syndrome, Barth Syndrome(Cardioskeletal
myopathy)
 Lysophospholipids(Lysolecithin): oxidized lipoproteins
 Intermediates of metabolism of phosphoglycerol
 Promote atherosclerosis
 Plasmalogens: 10% of PL in brain and muscle (mainly myocardium)
Phospholipids contd……
-R1.C=O-CH=CH-R1

26. Respiratory Distress Syndrome(RDS)
 Dipalmitoyl Phosphatidylcholine keeps lung
alveoli intact at low surface tension or low breathing
effort in new born babies
 Deficiency of DPL causes INFANT RDS
 Treatment: Aerosol, Asthalin, Nebulizer,

27. Sphingomyelin

28. Sphingomyelins contd…
 Sphingomyelins: Brain and nerve tissue
 FA + phosphoric acid + choline + sphingosine
 Only sphingolipid that contains phosphate but no sugar
 Amphipathic nature
 Relative concentration of lecithin and sphingomyelin:
important in bile and amniotic fluid
 L:S is 5 at term (L:S =1 means Respiration Distress Syn)

29. Sphingolipidoses
 Symptoms:
 Mechanism: (Activator Protein+Lysosomal lipid acid hydrolase)
missing leads to sphingolipid accumulation  Neurological
degradation
 Diagnosis:
 Autosomal recessive Niemann Pick Type A and Type B
 Febry Disease, Tay-Sachs Disease, Gaucher Disease

30. Glycolipids or Glycosphingolipids
 Important in nervous tissue and cell membranes
(Glycocalyx on outer membrane leaflet).
 Cerebrosides: (no phosphate)
 Glucocerebroside: Ceramide + glucose: Extraneural
 Galactocerebroside: Ceramide + galactose: Myelin
 Globoside: Ceramide + oligosaccharides
 2 or more hexoses or hexosamines + ceramide
 Lactosyl ceramide: Ceramide + glucose + galactose
(found in RBC membrane)
Hint: Ceramide = Sphingosine + Fatty Acid

31.  Gangliosides:
 Ceramide oligosaccharide + NANA
 Ceramide + Glucose + Galactose + NANA (GM1)
 Stability of paranodal junctions and ion channels
Glycolipids
Why Cholera is Toxic?
GM1 ganglioside:
Receptor binds with
vibrio cholera toxin
to secrete Cl- ions in
intestinecholera

32. Cerebrosides and Gangliosides
 Glycosphingolipids (cerebrosides and
gangliosides)
 Glycolipids (glycosphingolipids)
have a fatty acid, sphingosine, and
carbohydrate
 Cerebrosides have a single sugar
linked to ceramide
 Gangliosides (sphingolipids) have
oligosaccharides polar head groups +
one N-Acetyl-Galactosamine(NAG)
+ residues of N-acetylneuraminic acid
(NeuAc) or sialic acid
Ganglioside
(A sphingolipid)

33. Gangliosidosis Harper p218
Ganglioside Storage Diseases:
Gangliosidosis(GM1) (Cer-Glu-Gal-GalNAc-
Neu5Ac-Gal deposits)
Tay-Sachs Disease(GM2) (Cer-Glu-Gal-
Neu5Ac-Gal N Ac deposits) bme
(GM3) (Cer-Glu-Gal-Neu5-Ac deposits)
Gaucher’s Disease (Cer-Glu deposits) bbls
Sandhoff’s Disease (Cer-Glu-Gal-Gal-N-Ac
deposits)
Fabry Disease (Cer-Glu-Gal-Gal
deposits) sk
 Metachromatic Leukodystrophy(Cer-Gal-SO4) b
Case: 6 month baby presented regressed growth,cherry-red
spot in retina. Dr Tay-Sach defined it.

34. 25 y lady presented liver, spleen large, bone pain,
glucosylceramide deposits- Dr Gaucher defined it.
 Type 1: in 5-16 years
Lab: Pancytopenia, bleeding, Gaucher Cells
Symptoms:Bone pain,Bone cries
 Type 2:Hepatosplenomegaly
Symptoms:Neurodegeneration,
Visceral damage, Death
 Type 3:Bone Cries, Neurodegeneration
 Diagnosis: in X-Ray, flask shape
femur, β-Glucosidase deficiency
 Treatment: β-Glucosidase
ERT(Imiglucerase)
,Velaglucerase,Taliglucerase
Miglustat

35. Gaucher’s disease: lysosomal disorder
 Symptoms
 Bone marrow failure,
 Unable to walk
 Anemia,
 Thrombocytopenia
 Hepatosplenomegaly
 Glycosphingolipid lysosomal
FABRY DISEASE in brain
 Multi-system inborn-error
disorder in lysosomes
 Mechanism:
 Lysosomal storage disease due to
HYDROLASE enzymes (beta glucosidase)
 Glycolipid breakdown
 Therapy:
 Enzyme Replacement Therapy
 Iminosugar given to stop substrate flow
 Chaperones
Chabra N. page no 51

36. Niemann Pick Disease
 Autosomal recessive
 Symptom: Hepatosplenomegaly, Neurodegeneration
 Mechanism: Sphingomyelinase deficiency on Chr 11
 Lab: High Sphingomyelin in Monocyte-Macrophase
 Treatment:
 Transplantation of Liver, Bone Marrow, Amniotic cells
 Miglustat, ERT

37. How molecules cause Sphinolipidoses?
Sphingomyelin
NIEMANN PICK DISEASE lsb
Shingomyelinase
bbls GAUCHER DISEASE KRABBE DISEASE nb
Glucosidase Galactosidase
Glucocerebroside Ceramide Galactocerebroside
FARBER DISEASE bbsg
Ceramidase
Sphingosine

38. 63 y man had gastric pain.COX inhibitor gave relief.
Arachidonic Acid
Platelet Cycloxygenase
CELECOXIB
PG G2
PG H2

39. 45 y man had cardiac pain. Low dose aspirin gave relief.
Arachidonic Acid
Platelet Cycloxygenase
ASPIRIN
PG G2
PG H2

40. Metachromatic Leucodystrophy
 Physical S/S: Defective locomotion, weakness, ataxia,
hypotonia, paralysis,Speech difficulty,Optic trophy
 Enzyme Aryl Sulphatase A deficient
 Cerebroside/Sulphatide 1:4 in brain(3:1 normal)
Diagnosis: Infantile in <3 yrs or Dementia in Adult type
 Physical S/S: Skin rash(raddish purple), Painful legs or
neuropathy, Thrombosed blood vessels, Renal Failure,
Frequent urine, Cardiac pain, Cataract and Eye opacity
 Enzyme α-Galactosidase deficient
 GlobotriosylCeramide deposits
Fabry Disease

41. Lipid Storage Disease Harper p289

42. Precursor and derived lipids
Unsaponifiable compounds obtained by hydrolysis
of simple or compound lipids
 Fatty aldehydes
 Glycerols and other alcohols
 Fatty acids (Arachidonic acid)
 Steroids (Cholesterol)
 Ketone bodies
(acetaldehyde,acetone,HB)
 Thromboxanes
 Leukotrienes
 Prostaglandins
 Organic Bile Acids
 Steroid compounds
 Lipid-soluble vitamins (D)
 Hormones

43. Steroids
 Complex molecules consisting of four fused carbon
rings
Cyclo-pentano-perhydro-
phenanthrene ring (CPP)
Cholesterol: 3-hydroxy-5,6-cholestene

44. Cholesterol
 Atherosclerosis
 Precursor to:
 Bile acids
 Adrenocortical hormones
 Sex hormones
 Vit D
 Cardiac glycosides
 Plasma membrane and plasma lipoproteins
 Occurs in animals only, not plants
Phospholipids+Cholesterol+Bile AcidsBile. High CGallstones in Gall Bladder
High Cholesterol deposits in coronary/carotid artery Atherosclerosis/Cardiac arrest

45. Cholesterol
 Asymmetry makes many possible stereoisomers
 Chair and Boat form:
Clinical Biochemistry: lab tests
Blood Cholesterol 150-250 mg/dL
Lipid profile: HDL-C(male 35-55; female 45-65 mg/dL);
Triglycerides(male 60-165; female 40-140 mg/dL);LDL-C(>150 mg/dL); VLDL-C(25-45 mg/dL)
Medical Biochemistry: Physiochemical basis of diseases
Atherosclerosis, Lipid storage Diseases, Antioxidant Action, Lipoprotein Disorders

46. Eicosanoids
Lipolysis, Inflammation, BP, Platelet aggregation, Reproduction, Respiratory, GIT, Kidney
1. 65 y man had head grinding.
EPA+DHA daily 2 tab gave relief.
2. 63 y man had gastic pain.COX
inhibitor gave relief.
3. 45 y man had cardiac pain. Low
dose aspirin gave relief.
• Eicosapentanoic acid
• Docosahexaenoic acid
Derived Lipid Molecules
 Prostaglandins: Metabolic stimulators;
PGE2,PGF2,PGI2,PGI2
 Thromboxanes: Oxidative Pathway; TxA2
 Leukotrienes: Immunostimulators; LTA4, etc
 Lipoproteins: Transporters

47. Polyprenoids
 Not steroids
 Ubiquinone: respiratory chain in mitochondria
 Dolichol: glycoprotein synthesis
 Malondialdehyde
 Endoperoxide
 Hydroperoxide
Free Radicals by Lipid Peroxidation

48. Amphipathic Lipids
 Lipid bilayer
 Micelle
 Oil-Water or Bile Emulsion
 Liposomes
 Drug carriers

49. MCQ
 Fatty acids have:
 Galactosyl ceramide has:
 Gangliosides are made of:
 Antioxidants are;
 Body fat is made of:
 Essential fatty acids are:
 Lecithin contains:?; Cephalin contains:?
 Sphingomyelin is made of:
 Phospholipid contains:
 Cardiolipin is made of:
 Plasmalogen is made of:
 Cholesterol contains:
 Prostaglandins are: ……with functions……..
 Ecosanoids are:
 Deposits in Gaucher Disease..;Fabry Disease…;Tay-Sach Disease…

50. University Questions
 Define lipids. Give the classification of lipids in detail.
 Discuss structure and functions of phospholipids(10)
or Phospholipids(5)
 Prostaglandins with their physiological and
biochemical functions
 Short Note on:
 Essential Fatty acids
 Geometric isomerism
 PUFA
 Eicosanoids
 Dietary fibers
 Gaucher Disease, Fabry Disease, Tay-Sach Disease