Lipids and cell membrane

University of Tripoli, Faculty of Medicine

Department of Biochemistry and molecular biology
by Dr: Fahima Alnagar

LECTURE 1: 7.5.2022
 OBJECTIVES:

1. Define simple and complex lipids and identify the lipid classes in each group.
2. Indicate the structure of saturated and unsaturated fatty acids, explain how the chain length and degree of unsaturation
influence their melting point, give examples, and explain the nomenclature.
3. Explain the difference between cis and trans carbon–carbon double bonds.
4. Describe how eicosanoids are formed by modification of the structure of unsaturated fatty acids; identify the various
eicosanoid classes and indicate their functions.
5. Outline the general structure of triacylglycerols and indicate their function.
6. Outline the general structure of phospholipids and glycosphingolipids and indicate the functions of the different classes.
7. Appreciate the importance of cholesterol as the precursor of many biologically important steroids, including steroid
hormones, bile acids, and vitamins D. Recognize the cyclic nucleus common to all steroids.
8. Explain why free radicals are damaging to tissues and identify the three stages in the chain reaction of lipid peroxidation that
produces them continuously.
9. Recognize that many lipid molecules are amphipathic, having both hydrophobic and hydrophilic groups in their structure,
and explain how this influences their behavior in an aqueous environment and enables certain classes, including
phospholipids, sphingolipids, and cholesterol, to form the basic structure of biologic membranes.
10. describe how antioxidants protect lipids from peroxidation by either inhibiting chain initiation or breaking the chain.
 Lipids

• Heterogenous group of organic substances in plant and animal tissues, and related either
actually or potentially to the fatty acids.
• Chemically they are various types of esters of different alcohols. In addition to alcohol and
fatty acids, some of the lipids may contain phosphoric acid, nitrogenous base and
carbohydrates.
• Lipids are group of compounds, including fat, oils, steroids, waxes, and related compounds.
• It contains H, O, C and sometimes P.
Properties of lipids:

1. Relatively insoluble in water.

2. Solubility in one or more organic solvents, such as ether, chloroform,
benzene, acetone, etc, so called fat solvents.
3. Some relationship to the fatty acids as esters.
4. Possibility of utilisation by living organisms.
The importance of lipids:

1) Lipids are important dietary constituent and acts as fuel in the body. In some respects lipid is even
superior to carbohydrates as a raw material for combustion (burning), since, it yields more energy
per gm (9.5 C/gm) as compared to carbohydrates (4.0 C/gm).
2) They are dietary constituents of high energy, the fat-soluble vitamins and the essential fatty acids.
3) Can be stored in the body in almost unlimited amount in contrast to carbohydrates.
4) Fat is stored in adipose tissue which serves as a thermal insulator in the subcutaneous tissues
and around certain organs like kidney.
5) Components of hormones and precursors for prostaglandin synthesis.
6) Combinations of lipid and protein (lipoproteins) are important cellular constituent, both in the cell
membrane and in the mitochondria, and serving also as the means of transporting lipids in the
blood.
7) Cell messengers.
 Classification of lipids

I. Simple Lipids: II. Compound Lipids: Esters of fatty acids III. Derived Lipids IV. Miscellaneous
containing groups, other than, and in addition, to
Esters of fatty an alcohol and fatty acids. Derivatives obtained by hydrolysis of •Aliphatic
acids with various those given in group I and II, which still hydrocarbons include
alcohols: (a)Phospholipids: fats containing in addition to possess the general characteristics of isooctadecane found
fatty acid and glycerol, a phosphoric acid lipids. in liver fat and certain
(a) Neutral fats residue, a nitrogenous base and other (a) Fatty acids may be saturated, hydrocarbons found in
(Triacylglycerol, substituents. unsaturated or cyclic. bees wax and plant
TG): These are
(b) Monoglycerides (Monoacylglycerol) waxes.
triesters of fatty ▪ phosphatidyl choline (Lecithin), phosphatidyl
and Diglycerides (Diacylglycerol). • Carotenoids
acids with ethanolamine (Cephalin), phosphatidyl inositols
(c) Alcohols •Squalene is a
glycerol. (Lipositols), phosphatidyl serine, plasmalogens,
• Straight chain alcohols are water hydrocarbon found in
sphingomyelins, etc.
(b) Waxes: insoluble alcohols of higher molecular shark and mammalian
(b) Glycolipids: Lipids containing carbohydrate weight obtained on hydrolysis of liver and in human
are esters of fatty moiety. They contain a special alcohol called waxes. sebum.
acids with higher sphingosine or sphingol and nitrogenous base in • Cholesterol and other steroids • Vitamins E and K.
monohydroxy addition to fatty acids but does not contain including Vit D.
aliphatic alcohols. phosphoric acid or glycerol. These are of two • Alcohols containing the β-ionone ring
types: include Vit A and certain carotenoids.
• Glycerol.
• Cerebrosides
• Gangliosides
(c)Sulpholipids: Lipids characterised by
possessing sulphate groups.
(d) Aminolipids (Proteolipids)
(e) Lipoproteins: Lipids as prosthetic group to
proteins.
1. Alcohols
A. Glycerol:
•is commonly called as “glycerin” it is the simplest trihydric alcohol as it contains three hydroxyl groups in
the molecule
•It is colourless oily fluid with a sweetish taste.
•It is miscible with water and alcohol in all proportions but is almost insoluble in ether.
Source:
Industrial
• It is obtained as a by-product of soap manufacture.
• It is also obtainable in the fermentation of glucose by changing conditions in such a way as to decrease
the formation of CO2 and alcohol.
Physiological
• Endogenous source: Main source is from lipolysis of fats in adipose tissue.
• Exogenous source: Dietary Approx. 22 per cent of glycerol directly absorbed to portal blood from the gut.
B. Unsaturated Alcohols
Among the unsaturated alcohols found in fats, many of them are pigments. These include:
(a) Phytol (Phytyl alcohol): A constituent of chlorophyll.
(b) Lycophyll: A polyunsaturated dihydroxy alcohol which occurs in tomatoes as a purple
pigment.
(c) Carotene: Easily split in the body at the central point of the chain to give two molecules of
alcohol, vitamin A.
(d) Sphingosine or sphingol: An unsaturated amino alcohol present in body as a constituent of
phospholipid,sphingomyelin and various glycolipids.
 2. Fatty acids: A fatty acid (FA) may be defined as an organic acid that occurs in a natural triglyceride and
is a monocarboxylic acid ranging in chain length from C4 to about 24 carbon atoms. FA are obtained from
hydrolysis of fats.
1. Most lipids are made of fatty acids.
2. Fatty acids made of heads and tails:
• Heads: COOH (carboxyl group) at one end
• Tails: long chain C bonded H (hydrocarbon chain).
3. Long unbranched carboxylic acids.
4. Are usually straight-chain derivatives containing:
a. an even number )‫ (رقم زوجي‬of carbon atoms in natural fats.
b. Odd numbered chain fatty acids )‫(رقم فردي‬: Rare, found in some plants & marine organisms. E.g.,
propionic acid (3:0), Heptadecanoic acid or margaric acid (17:0)
5.The chain may be saturated (containing no double bonds) or unsaturated containing one or more double
bonds).
 according to the presence or absence of double bonds fatty acids are:
A. Saturated fatty acids:

- Full of hydrogen.
- Solid at room temperature WHY?
- All contains single bonds
- Straight chains.
 Saturated fatty acids

a. Short chain long chain

b. Contain 2-10C atoms More than 10C atoms
c. Volatile Non-volatile
1) Acetic acid: 2C atoms Palmitic acid: 16C
atoms
CH3COOH CH3 (CH2)14 COOH
2) Butyric acid: 4C atoms Stearic acid: 18C
atoms
CH3 CH2 CH2 COOH CH 3 (CH2)16COOH
3) Caproic acid: 6C atoms Lignoceric acid: 24C
CH3 (CH2)4 COOH CH 3 (CH2)22 COOH

- Saturated fatty acids may be envisaged as based on acetic acid (CH3-COOH) as the first member of the series in which -
CH2- is progressively added between the terminal CH3- and -COOH groups.
- Other higher members of the series are known to occur, particularly in waxes.
- A few branched-chain fatty acids have also been isolated from both plant and animal sources. Saturated fatty acids having
10 carbon or less number of carbon atoms are also called as lower fatty acids, e.g. acetic acid, butyric acid, etc.
- Saturated fatty acids having more than 10 carbon atoms are also called higher fatty acids, e.g. palmitic acid, stearic acid,
etc. Milk contains significant amount of lower fatty acids.
B. Unsaturated Fatty Acids
- Not full of hydrogen
- Contain one or more double bonds
- Liquid at room temperature WHY?
- Kinked or bent (not straight).

Fatty acids may be subdivided as follows: They are classified further according to degree of unsaturation.
1. Monounsaturated (monoethenoid, monoenoic) acids, containing one double bond.
Their general formula is Cn H2n–1 COOH
Example: Oleic acid C17H33 COOH is found in nearly all fats (formula 18: 1; 9).
2. Polyunsaturated (polyethenoid, polyenoic) acids, containing two or more double bonds.
There are three polyunsaturated fatty acids of biological importance.
i. Linoleic acid series (18: 2; 9, 12): It contains two double bonds between C9 and C10; and between C12 and
C13. Their general formula is CnH2n–3 COOH.
Dietary sources: Linoleic acid is present in sufficient amounts in peanut oil, corn oil, cottonseed oil, soyabean
oil and egg yolk.
ii. Linolenic acid series (18: 3; 9, 12, 15): It contains three double bonds between 9 and 10; 12 and 13; and 15
and 16. Their general formula is CnH2n–5 COOH.
Dietary Source: Found frequently with linoleic acid, but particularly present in linseed oil ‫كتان‬, rapeseed oil ‫بذور‬
‫اللقت‬, soybean oil, fish visceras and liver oil (cod liver oil).
iii. Arachidonic acid series (20: 4; 5, 8, 11, 14): It contains four double bonds. Their general formula:CnH2n–7
COOH
Dietary source: Found in small quantities with linoleic acid and linolenic acid but particularly found in peanut
oil. Also found in animal fats including Liver fats.
Note: These three polyunsaturated fatty acids, linoleic acid, linolenic acid and arachidonic acid are called as
“Essential fatty acids (EFA)”. They have to be provided in the diet, as they cannot be synthesised in the body.
•Eicosanoids: These compounds, derived from eicosa- (20-carbon) polyenoic fatty acids, comprise the
prostanoids, leukotrienes (LTs), and lipoxins (LXs).
•Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs).

prostaglandin thromboxane
 According to the geometric configuration of unsaturated fatty acids:

- Cis fatty acids (both part of the chain adjacent to the double bond are at the same side of the double bond).
Most naturally occurring unsaturated fatty acids have cis bonds (healthy fats) C=C
H H

- Trans fatty acids (the two parts or the chain adjacent to the double bond are in opposite side or the
double bond) this is unhealthy fats such as hydrogenated fats (margarine).
C=C H
H
According to biological (also called Nutritional classification)
1. Essential fatty acids (EFA): Three polyunsaturated fatty acids, linoleic acid, linolenic acid
and arachidonic acid are called “essential fatty acids” (EFA). They cannot be synthesised in
the body and must be provided in the diet.
Lack of EFA in the diet can produce growth retardation and other deficiency manifestation
symptoms.
Which EFA is Important?
Linoleic acid is most important as, arachidonic acid can be synthesised from linoleic acid by a
three stage reaction by addition of acetyl-CoA. Pyridoxal phosphate is necessary for this
conversion. Biologically arachidonic acid is very important as it is precursor from which
prostaglandins and leukotrienes are synthesised in the body.
Human deficiency of EFA: Some cases of
• Eczema like dermatitis,
• Degenerative changes in arterial wall
• Fatty liver in man may be due to EFA deficiency.
There are also some reports that administration of EFA in such cases may produce:
– Some improvement of eczema in children kept on skimmed milk, prevent fatty liver (some cases)
and lowering of cholesterol levels.
Infants and babies with low fat diet develop typical skin lesions which has shown to be improved with
EFA (linoleic acid).
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid which is synthesized from α-linolenic
or obtained directly from dietary fish oil. This fatty acid is present in high concentrations in retina,
cerebral cortex, testes and sperms.
DHA is particularly needed for development of the brain and retina and is supplied via the placenta
and milk. In EFA deficiency, nonessential polyenoic acids of the W9 family replace the essential fatty
acids in phospholipids (PL), other complex lipids and membranes.
Clinical Aspect:
Low blood levels of DHA have been reported in patients with Retinitis Pigmentosa.
Abnormal metabolism of EFA, which may be concerned with dietary insufficiency, has been noted
in a number of disease like cystic fibrosis, hepatorenal syndrome, Crohn’s disease, acrodermatitis
enteropathica, Sjögren’s syndrome, Cirrhosis and Reye’s syndrome.
2. Non essential: Synthesized by animals. All the others.
Fatty acids nomenclature:
Genevan system:
•Saturated acids end in -anoic, eg, octanoic acid, and unsaturated acids with double bonds end in -
enoic, eg, octadecenoic acid (oleic acid).
•Carbon atoms are numbered from the carboxyl carbon (carbon No.1). The carbon atoms adjacent to
the carboxyl carbon (Nos. 2, 3, and 4) are also known as the α, β, and γ carbons, respectively, and
the terminal methyl carbon is known as the ω or n-carbon.
•Delta )Δ(: for indicating the number and position of the double bonds (e.g., Δ9 indicates a double
bond between carbons 9 and 10 of the fatty acid.

Oleic acid n-9 (n minus 9) is equivalent to ω9

• Omega )ω9): indicates a double bond on the ninth carbon counting from the ω- carbon. In animals,

additional double bonds are introduced only between the existing double bond (eg, ω9, ω6, or ω3) and the

carboxyl carbon, leading to three series of fatty acids known as the ω9, ω6, and ω3 families, respectively.

• The carbon chains of saturated fatty acids form a zigzag pattern when extended, as at low temperatures.

• At higher temperatures, some bonds rotate, causing chain shortening, which explains why biomembranes

become thinner with increases in temperature.

 I) Simple lipids

A. Neutral fats (triglycerides or triacylglycerol)

- Neutral fats (TG) are all triesters of the trihydric alcohol, glycerol with various fatty acids.
- R1 R2 R3 represent fatty acid chains which may or may not all be the same.
- Naturally occurring fats have apparently the D-structural configuration.
- The most common type of lipid.

- On hydrolysis, it gives glycerol and 3 fatty acids.

Physical Properties:
1. Neutral fats are colourless, odourless and tasteless substances. The colour and taste of some
of the naturally occurring fats is due to extraneous substances.
2. Solubility: They are insoluble in water but soluble in organic fat solvents.

3. Specific gravity: The specific gravity of all fats is less than 1.0, consequently all fats float in
water.

4. Emulsification: Emulsions of fat may be made by shaking vigorously in water and by

emulsifying agents such as gums, soaps and proteins which produce more stable emulsions.
5. Melting point (MP) and consistency: The hardness or consistency of fats is related to their MP
glycerides of lower FA melt at lower temperature than those of the higher fatty acids, and the
unsaturated fatty acids glycerides at still lower temperature.
Lipases are enzymes which hydrolyse a triglyceride yielding fatty acids and glycerol.
Sites: Lipases are found in human body in following places.
(a) Lingual lipase in saliva
(b) Gastric lipase in gastric juice
(c) Pancreatic lipase in pancreatic juice
(d) Intestinal lipase in intestinal epithelial cell
(e) adipolytic lipase in adipose tissue
(f) Serum lipase.
Chemical Properties
1. Hydrolysis
The fats may be hydrolysed with:
• Super heated steam
• By acids, or alkalies
• By the specific fat splitting enzymes lipases
Saponification: Hydrolysis of a fat by an alkali is called saponification. The resultant products are
glycerol and the alkali salts of the fatty acids, which are called “soaps”.
2. Hydrogenation:
It is addition of hydrogen at the double bond of the unsaturated fatty acids from saturated acids e.g.,
margarine. Oils which are liquid at ordinary room temperature, on hydrogenation become solidified.
3. Oxidation
Fats very rich in unsaturated fatty acids undergo oxidation at the double bond.
4. Rancidity
The unpleasant odour and taste developed by most natural fats on aging is referred to as
rancidity.
Cause of rancidity: Rancidity may be caused by the following:
• Hydrolysis of fat yields free fatty acids and glycerol and/or mono and diglycerides. Process
Is enhanced by presence of lipolytic enzymes lipases, which in the presence of moisture and
warm temperature bring about hydrolysis rapidly.
• By various oxidative processes, oxidation of double bonds of unsaturated glycerides may form
“peroxides”, which then decompose to form aldehydes of objectionable odour and taste. The
process is greatly enhanced by exposure to light.
Prevention of rancidity: Vegetable fats contain certain substances like vitamin E, phenols,
hydroquinones, tannins and others which are antioxidants and prevents development of rancidity.
Hence vegetable fats preserve for longer periods than animal fats.
B) Waxes:
1. They are esters of fatty acids and long chain alcohol (longer than glycerol).
2. Not easily hydrolyzed as triacylglycerol and usually solid. e.g., vitamin A esters, vitamin D esters and
cholesterol esters.
3. Waxes coat feathers, water proofing birds and insulating them from water.
II) Complex (compound) lipids
a. Phospholipids: contain
1. Fatty acids
2. An alcohol/in glycerophospholipids the alcohol is glycerol and in sphingophospholipids the alcohol is
sphingosine.
3. A phosphoric acid residue
4. They frequently have nitrogen containing bases and other substituents. in glycerophospholipids the alcohol is
glycerol and in sphingophospholipids the alcohol is sphingosine.
5. Phospholipids are the main lipid constituents of membranes.
6. Phospholipids may be regarded as derivatives of phosphatidic acid, in which the phosphate is esterified with
the -OH of a suitable alcohol.
•Glycerophospholipids. The common glycerophospholipids are diacylglycerols linked to head-
group alcohols through a phosphodiester bond. Phosphatidic acid, a phosphomonoester, is the
parent compound. Each derivative is named for the head-group alcohol (X), with the prefix
“phosphatidyl-.”
1) Phosphatidylcholine (Lecithin):
•Occur in Cell Membranes
•containing choline are the most abundant phospholipids of the cell membrane and represent a large
proportion of the body’s store of choline.
•Choline is important in nervous transmission, as acetylcholine, and as a store of methyl groups.

Dipalmitoyl lecithin: is a very effective surface active agent and a major constituent of the surfactant
preventing adherence, due to surface tension, of the inner surfaces of the lungs.
Its absence from the lungs of premature infants causes respiratory distress syndrome.
2) Phosphatidylethanolamine (cephalin) & phosphatidylserine:
(Found in most tissues) differ from phosphatidylcholine only in that ethanolamine or serine, respectively,
replaces choline.

Phosphatidylethanolamine (cephalin) & phosphatidylserine

3) Cardiolipin:
• Is a major lipid of mitochondrial membranes and is essential for the mitochondrial function.
• Two phosphatidic acids share a single glycerol.
• Decreased cardiolipin levels or alterations in its structure or metabolism cause mitochondrial dysfunction in
aging and in pathologic conditions including heart failure, hypothyroidism, and Barth syndrome
(cardioskeletal myopathy).
4) Plasmalogens occur in brain & muscle:
• These compounds constitute as much as 10% of the phospholipids of brain and muscle.
• Plasmalogens resemble phosphatidylethanolamine but possess an ether link on the C1 carbon
instead of the ester link found in acylglycerols.
• The function of plasmalogens remain poorly understood, but it has been suggested that they
may have a protective effect against reactive oxygen species.
II. Phosphosphingosides:

Alcohol present is sphingosine (also called as sphingol), an unsaturated amino alcohol

Sphingomyelins:
• found in the nervous system, found in the outer leaflet of the cell membrane lipid bilayer and are particularly
abundant in specialized areas of the plasma membrane known as lipid rafts.
• found in large quantities in the myelin sheath surrounds nerve fibers.
• They are believed to play a role in cell signalling and in apoptosis.
• On hydrolysis, the sphingomyelins yield a fatty acid, phosphoric acid, choline, and a complex amino
alcohol, sphingosine (No glycerol).
• The combination of sphingosine plus fatty acid is known as ceramide, a structure also found in the
glycosphingolipids.
III) Phosphoinositides:
1. In this group, inositol is the alcohol, e.g. phosphatidyl inositol (lipositol).
2. Phosphorylated phosphatidylinositols (phosphoinositides) are minor components of cell
membranes, but play an important part in cell signalling and membrane trafficking.
3. Phosphoinositides may have 1, 2, or 3 phosphate groups attached to the inositol ring.
4. Phosphatidylinositol 4,5-bisphosphate (PiP2), for example, is cleaved into diacylglycerol and
inositol trisphosphate upon stimulation by a suitable hormone agonist, and both of these act as
internal signals or second messengers.
❖ Functions of Phospholipids
1. Structural: Phospholipids participate in the lipoprotein complexes which are thought to constitute the
matrix of cell walls and membranes, the myelin sheath, and of such structures as mitochondria and
microsomes.
2. Role in enzyme action: Certain enzymes require tightly bound phospholipids for their actions, e.g.
mitochondrial enzyme system involved in oxidative phosphorylation.
3. Role in blood coagulation: Phospholipids play an essential part in the blood coagulation process.
4. Role in lipid absorption in intestine: Lecithin lowers the surface tension of water and aids in
emulsification of lipid water mixtures, a prerequisite in digestion and absorption of lipids from
gastrointestinal tract (GI) tract.
5. Role in transport of lipids from intestines: Exogenous TG is carried as lipoprotein complex,
chylomicrons, in which PL takes an active part.
6. Role in transport of lipids from liver: Endogenous TG is carried from Liver to various tissues as
lipoprotein complex.
7. Role in electron transport: Probably PL helps to couple oxidation with phosphorylation and maintain electron
transport enzymes in active conformation and proper relative positions.
8. Ion transport and secretion: Phospholipids are in some way implicated in the mechanism of secretion is
suggested by the observation that phospholipids, especially phosphatidic acid and phosphoinositides turnover
is proportional to the rate of secretion of cells liberating such products as hormones, enzymes, mucins and
other proteins.
9. Membrane phospholipids as source of arachidonic acid: Phospholipids of membrane are hydrolysed by
phospholipase A2 and provide the unsaturated fatty acid arachidonic acid, which is utilised for synthesis of
Prostaglandins and leukotrienes.
10. Insulation: Phospholipids of myelin sheaths provide the insulation around the nerve fibres.
11. Cofactor: Phospholipids are required as a cofactor for the activity of the enzyme lipoprotein lipase and
triacylglycerol lipase.
12. Role of phosphatidyl inositides metabolite in Ca++ dependent hormone action: Some signal must provide
communication between the hormone receptor on the plasma membrane and intracellular Ca++ reservoirs.