Lipids of Physiologic Significance

Carbon (C)
Hydrogen (H)
Oxygen (O)
 Lipids
 Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic
molecules .
 Because of their insolubility in aqueous solutions,
1. body lipids are generally found compartmentalized, as in the case of membrane-
associated lipids
2. or droplets of triacylglycerol in adipocytes,
3. or transported in plasma in association with protein, as in lipoprotein particles.

 Lipids are a major source of energy for the body,

 they provide the hydrophobic barrier that permits partitioning of the aqueous
contents of cells and subcellular structures.
 Lipids serve additional functions (e.g. some fat-soluble vitamins have regulatory
or coenzyme functions, prostaglandins and steroid hormones play major roles in
the control of the body’s homeostasis).
 Not surprisingly, deficiencies or imbalances of lipid metabolism can lead to some
of the major clinical problems encountered by physicians, such as atherosclerosis,
diabetes, and obesity.
Importance of Lipids:
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.
7. Storage.
 BIOMEDICAL IMPORTANCE
 The lipids are a heterogeneous group of compounds, including fats, oils,
steroids, waxes, and related compounds.

 They have the common property of being

1 - relatively insoluble in water and
2 - soluble in nonpolar solvents such as ether and chloroform.

 They are important dietary constituents not only because of the high
energy value of fats, but also because essential fatty acids and fat-soluble
vitamins.

 Dietary supplementation with long chain w fatty acids is believed to have

beneficial effects in a number of chronic diseases, including cardiovascular
diseases.
 LIPIDS CLASSIFICATION - SIMPLE OR COMPLEX
 1. Simple lipids - include fats and waxes which are esters of fatty acids with various alcohols:
a. Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state. (Room
temperature)
b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols.
 2. Complex lipids - are esters of fatty acids containing groups in addition to an alcohol and
one or more fatty acids. They can be divided into three groups:
 a. Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric
acid residue. They frequently have nitrogen-containing bases (eg, choline) and other
substituents.
b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and
carbohydrate.
c. Other complex lipids: Lipids such as sulfolipids and amino lipids. Lipoproteins may also
be placed in this category.

3. Precursor and derived lipids: These include fatty acids, glycerol, steroids, other
alcohols, fatty aldehydes, ketone bodies, hydrocarbons, lipid-soluble vitamins and
micronutrients, and hormones.
 Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are
termed neutral lipids.
 FATTY ACIDS ARE CARBOXYLIC ACIDS
 Fatty acids occur in the body mainly as esters in natural fats and oils, but are
found in the unesterified form as free fatty acids, a transport form in the plasma.

 Fatty acids that occur in natural fats usually contain an even number of carbon
atoms.
 Overview of FAs
• A fatty acid consists of a hydrophobic hydrocarbon chain with a terminal
carboxyl group.
• At physiologic pH, the terminal carboxyl group (–COOH) ionizes, becoming –
COO-

• This anionic group has an affinity for water, giving the fatty acid its amphipathic
nature (having both a hydrophilic and a hydrophobic region).
• However, for long-chain fatty acids (LCFAs), the hydrophobic portion is
predominant.

• These molecules are highly water insoluble, and must be transported in the
circulation in association with protein.

• More than 90% of the fatty acids found in plasma are in the form of fatty acid
esters (primarily triacylglycerol, cholesteryl esters, and phospholipids) contained
in circulating lipoprotein particles

• Unesterified (free) fatty acids are transported in the circulationin association with
albumin.
 Major lipids of physiological significance
• There are many different Fatty Acids but all have same basic structure.
• They are made of chains of carbon with a methyl group at one end (CH3)
and a carboxyl group at the other end (COOH).
• What makes one fatty acid different from another is the length of the
carbon chain.
 Fatty Acids
1. Fatty acids exist “free” in the body (that is, they are unesterified), and are also found
as fatty acyl esters in more complex molecules, such as triacylglycerols.

2. Plasma free fatty acids (transported on serum albumin) are in route from their point
of origin (triacylglycerol of adipose tissue or circulating lipoproteins) to their site of
consumption (most tissues).

3. Free fatty acids can be oxidized by many tissues — particularly liver and muscle—to
provide energy.
4. Fatty acids are also structural components of membrane lipids, such as
phospholipids and glycolipids.

5. Fatty acids are attached to certain intracellular proteins to enhance the ability of
those proteins to associatewith membranes.

6. Fatty acids are also precursors of the hormone-like prostaglandins.

7. Esterified fatty acids, in the form of triacylglycerols stored in adipose cells, serve as
the major energy reserve of the body.
 Saturation of fatty acids
 The chain may be
 saturated (containing no double bonds) or
 unsaturated (containing one or more double bonds). – mono- or polyunsaturated.
 When double bonds are present, they are nearly always in the cis rather than in the trans
configuration.
 The introduction of a cis double bond causes the fatty acid to bend or “kink” at that
position.
 If the fatty acid has two or more double bonds, they are always spaced at three-carbon
intervals.
 Note: In general, addition of double bonds decreases the melting temperature (Tm) of a
fatty acid, whereas increasing the chain length increases the Tm.
 Because membrane lipids typically contain LCFA, the presence of double bonds in some
fatty acids helps maintain the fluid nature of those lipids.

Fatty acids

Saturated Unsaturated
 Saturated Fatty Acids
• Each carbon atom is saturated with hydrogen
• There are no double bonds present between the carbon atoms (having no
points of unsaturation).
• They are generally solid at room temperature,
• Saturated fats- considered as harmful. It increases total cholesterol level
and TGs level.
• They are generally from animal sources.
• Examples: Butyric Acid in butter and Stearic Acid in meat
 Unsaturated Fatty Acids Contain One or More Double Bonds.
 Unsaturated fatty acids may be further subdivided as follows:

 1. Monounsaturated (monoethenoid, monoenoic) acids, containing one double bond.

 2. Polyunsaturated (polyethenoid, polyenoic) acids, containing two or more double
bonds.
 3. Eicosanoids: These compounds, derived from eicosa (20-carbon) polyenoic fatty
acids: leukotrienes (LTs), and lipoxins (LXs), prostaglandins (PGs),
prostacyclins(PGIs), and thromboxanes (TXs).

They have roles in:

•Inflammation
•Fever
•Regulation of blood pressure
•Blood viscosity
•Female conception
•Muscle cotraction
•Blood clotting
•Bronchocostriction
•Asthma.
 Divisions of unsaturated fatty acids

Unsaturated
Fatty acids

MUFA PUFA Eicosanoids

 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.
 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 sunflower, and soybean, and in fatty fish.

• They possess protective role on human health considered as beneficial for

consumpmtion.
 Chain lengths of fatty acids
 The carbon atoms are numbered, beginning with the carboxyl carbon as carbon 1.
 The number before the colon indicates the number of carbons in the chain, and those after
the colon indicate the numbers and positions (relative to the carboxyl end) of double
bonds.

 For example, arachidonic acid, 20:4 (5,8,11,14),

 is 20 carbons long and has 4 double bonds (between carbons 5–6, 8–9, 11–12, and 14–15).

 Note: Carbon 2, the carbon to which the carboxyl group is attached, is also called the α-
carbon, carbon 3 is the β-carbon, and carbon 4 is the γ-carbon.
 The terminal methyl carbon is called the ω-carbon regardless of the chain length.

 The double bonds in a fatty acid can also be denoted relative to the ω (or methyl-terminal)
end of the chain.
 Arachidonic acid is referred to as an ω-6 fatty acid acid (also an n-6,) because the terminal
double bond is six bonds in from the ω end.

 Another ω-6 fatty acid is the essential linoleic acid, 18:2(9,12).

 In contrast, α-linolenic acid, 18:3(9,12,15), is an essential ω-3 fatty acid.
 Fatty Acids Are Named After Corresponding Hydrocarbons

Various conventions use Δ for

indicating the number and position of
the double bonds for example, Δ9
indicates a double bond between
carbons 9 and 10 of the fatty acid;

ω9 indicates a double bond on the ninth

carbon counting from the ω-carbon.

In animals, three series of fatty acids

known as the ω9, ω6, and ω3 families.
 Essential fatty acids EFAs

 Two fatty acids are dietary essentials in humans because of our inability to
synthesize them:

1. linoleic acid, which is the precursor of ω-6 arachidonic acid, the substrate for
prostaglandin synthesis,
2. and α-linolenic acid, the precursor of other ω-3 fatty acids important for growth
and development.

 Plants provide us with the essential fatty acids.

 Arachidonic acid becomes essential if linoleic acid is deficient in the diet.

 Counteract the hardening effect of cholesterol in the arteries

 Help prevent CHD.
 Most Naturally Occurring Unsaturated Fatty Acids Have
cis Double Bonds
 A type of geometric isomerism occurs in unsaturated fatty acids, depending on the
orientation of atoms or groups around the double bonds, which do not allow rotation.
 If the acyl chains are on the same side of the bond, it is cis-.
 if on opposite sides, it is trans-.
 Double bonds in naturally occurring unsaturated long-chain fatty acids are nearly all
in the cis configuration, the molecules being “bent” 120° at the double bond.
 Increase in the number of cis double bonds in a fatty acid leads to a variety of possible
spatial configurations of the molecule—for example, arachidonic acid, with four cis
double bonds, is bent into a U shape.
 Trans double bonds alter these spatial relationships.

 Trans fatty acids are present in certain foods- Consumption of trans fatty acids is
now known to be is associated with increased risk of diseases including
cardiovascular disease and diabetes mellitus.
 Cis Fatty Acids
• Cis fatty acids occur when the hydrogen atoms are at the same side of the
double bond
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.
 Physical and Physiologic Properties of Fatty Acids Reflect Chain Length and
Degree of Unsaturation

• The melting points of even-numbered carbon fatty acids increase with chain
length and decrease according to unsaturation.

• A triacylglycerol containing three saturated fatty acids of 12 carbons or more is

solid at body temperature.
• In practice, natural acylglycerols contain a mixture of fatty acids tailored to suit
their functional roles.

• For example, membrane lipids, which must be fluid at all environmental

temperatures, are more unsaturated than storage lipids.
Triglycerides

Structure
• Glycerol + 3 fatty acids

Functions
• Energy source
• Form of stored energy in adipose tissue.
• Insulation and protection
 PHOSPHOLIPIDS ARE THE MAIN LIPID CONSTITUENTS OF
MEMBRANES
 Many phospholipids are derivatives of phosphatidic acid in which the phosphate
is esterified with one OH group of glycerol and the other two OH groups are
esterified to two long chain fatty acids (glycerophospholipids).

 Sphingolipids such as sphingomyelin, in which the phosphate is esterified to

sphingosine, a complex amino alcohol are also important membrane components.

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.
 Phosphatidylcholines (Lecithins) and Sphingomyelins Are Abundant in Cell
Membranes
 Glycerophospholipids containing choline, (phosphatidylcholines, commonly called
lecithins) are the most abundant phospholipids of the cell membrane and represent a
large proportion of the body’s store of choline.

 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 - respiratory distress syndrome.

• Sphingomyelins are found in the outer leaflet of the cell membrane lipid bilayer and
are particularly in large quantities in the myelin sheath that surrounds nerve fibers.

 Phosphatidylinositol Is a Precursor of Second Messengers

 Cardiolipin - this phospholipid is found only in mitochondria and is essential for the
mitochondrial function.
 GLYCOLIPIDS – GLYCOSPHINGOLIPIDS ARE
IMPORTANT IN NERVE TISSUES and IN THE CELL MEMBRANE
 Glycolipids are lipids with an attached carbohydrate or carbohydrate chain.
 They are widely distributed in every tissue of the body, particularly in nervous tissue such as
brain.
 They occur particularly in the outer leaflet of the plasma membrane, where they contribute to
cell surface carbohydrates which form the glycocalyx.
 The major glycolipids found in animal tissues are glycosphingolipids.
 Gangliosides, cerebrosides, globosides.
 They function in cell-cell recognition and communication and as receptors for hormones, etc.
 Sterols

Steroids are the compounds contains cyclic steroid

nucleus namely cyclo pentanophenanthrene ring.

Cholesterol
Although cholesterol is probably best known for its
association with atherosclerosis and heart disease, it has
a number of essential roles in the body.

Functions
– Bile acids
– Sex hormones
– Adrenal hormones
– Vitamin D
 Lipoproteins

Lipoproteins are the macromolecular

complex of lipids and proteins.
Chylomicrons,VLDL

Transportation of lipids in the blood.

Structure of lipoproteins: LDL

Hydrophobic lipids (TG, CE) in core;

HDL
 Lipid related disorders;-

Common disorders Uncommon disorders

Hypercholetrolemia Metabolic disorders of cerebrosides.
Hypertriglyceridemia Lipidoses / lipid storage diseases
Hyperlipoproteinemia Multiple sclerosis
CVD Infant respiratory distress syndrome
Fatty liver Xanthomatosis
Obesity