Part-One
Chemistry of lipids
 Digestion, Absorption,
 Secretion And Utilization

Objectives
Define lipid and its classification
 what is essential fatty acids , give an example
 Define cholesterol and is structure
 describe the biological importance of cholesterol
 Clinical importance “atherosclerosis “
Describe how fat is digested and absorbed
 What is Emulsification
Describe maldigestion and mal absorption of fat
 list GIT hormones and there role in fat digestion

Reference Books
 Marks´ Basic Medical Biochemistry A Clinical Approach, third edition, 2009
(M. Lieberman, A.D. Marks)
 Champe, P.C., Harvey, R.A. and Ferrier, D.R., Lippincott’s Illustrated
Reviews: Biochemistry, 4th or 5th Edition, Lippincott Williams & Wilkins,
Baltimore, MD 2008 or 2011.

Biomedical Importance
The lipids are a heterogeneous group of compounds,
including fats, oils, steroids, waxes.
 They have the common property of being:
Relatively insoluble in water and
Soluble in non-polar solvents such as ether &chloroform.

Importance :
 They are important dietary constituents because of:
a. Their high energy value
b. The fat-soluble vitamins and the essential fatty acids
contained in the fat of natural foods
 Fat is stored in adipose tissue, as a thermal insulator in
the subcutaneous tissues and around certain organs
 Non-polar lipids act as electrical insulators, allowing rapid
propagation of depolarization waves along myelinated nerves.

 Combinations of lipid and protein (lipoprotéines) serving
also as the means of Transporting lipids in the blood
 Knowledge of lipid biochemistry is necessary in
understanding many important biomedical areas such as
Obesity, diabetes mellitus,
Atherosclerosis, and the role of various polyunsaturated
fatty acids in nutrition and health.

 Simple Lipids
 Complex Lipids:

 Simple lipids: Esters of fatty acids with various alcohols.
Fats: Esters of fatty acids with glycerol.
Oils and Waxes are a good example
 Complex lipids: Esters of fatty acids containing groups
in addition to an alcohol and a fatty acid.
Example : Phospholipids: Lipids containing, in addition to
fatty acids and an alcohol, a phosphoric acid residue.

 Glycolipids : Lipids containing a fatty acid, sphingosine,
and carbohydrate.
 Other complex lipids: Lipids such as sulfolipids and
aminolipids. Lipoproteins may also be placed in this
category.

Fatty Acids
 Fatty acids are building block of most lipids,
 Having one polar carboxyl group (head) and a non-polar
hydrocarbon chain (tail).
 Fatty acids occur mainly as esters in natural fats and oils but do
occur in the unesterified form as free fatty acids, a transport
form found in the plasma.

 Fatty acids that occur in natural fats has even number
of carbon atoms.
 The chain may be saturated (no double bonds) or
unsaturated ( one or more double bonds).

 Thus, Saturated acids end in -anoic, e.g. octanoic acid, and
Unsaturated acids with double bonds end in -enoic, e.g.
octadecenoic acid (oleic acid).
 Carbon atoms are numbered from the carboxyl carbon (carbon
No. 1). the terminal methyl carbon is known as the ω or n-carbon.

 Various conventions use 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;
 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 (E.g., ω9, ω6, or ω3)

Unsaturated Fatty Acids Contain One or More
Double Bonds
Fatty acids may be further subdivided as follows:
 Monounsaturated containing one double bond.
 Polyunsaturated containing two or more double bonds.
 Eicosanoid: (20-Carbon) polyenoic fatty acids, comprise
 the Prostanoids, leukotrienes (LTs), lipoxins (LXs).
 Prostanoids include prostaglandins (PGs), prostacyclins
 (PGIs), and thromboxanes (TXs).

Some Common Examples

 Most Naturally Occurring Have cis Double Bonds.
 If on the same side of the bond, it is cis-, as in oleic acid
 if on opposite sides, it is trans-, as in “Elaidic acid,”
Geometric isomerismof Δ9, 18:1 fatty acids (oleic and Elaidic acids).

TRIACYLGLYCEROLS (TRIGLYCERIDES)*
===Are the main storage forms of fatty acids
 The triacylglycerols are esters of glycerol &fatty acids.
 Mono- and diacylglycerol wherein one or two fatty
acids are esterified with glycerol are also found in the
tissues.

 Enzymes readily distinguish between them and are
nearly always specific for one or the other carbon;
 E.g. Glycerol is always phosphorylated on sn-3 by
Glycerol kinase to give glycerol 3-phosphate and
not glycerol-1-phosphate .
This glycerol kinase enzyme is specifically present only in
liver

 All of the steroids have a similar cyclic nucleus
resembling phenanthrene (rings A, B, and C) to
which a cyclopentane ring (D) is attached.
 The carbon positions on the steroid nucleus are
numbered as shown in Figure
What is Cholesterol

Cholesterol Is a Significant Constituent of Many Tissues
 Cholesterol is widely distributed in all cells of the body but
 particularly in nervous tissue.
 It is a major constituent of the plasma membrane and
 major constituent of plasma lipoproteins.
 It is often found as cholesteryl ester, wherethehydroxyl
groupon position 3 is esterified with a long-chain fatty acid.
 It occurs in animals but not in plants.
HO

What are the physiologically
important roles of cholesterol ??

Steroids Play Many Physiologically Important Roles
Biochemically it is also of significance because it
is the precursor of a large number of equally important
steroids that include
Bile acids,
Adrenocorticalhormones,
Sex hormones,
D vitamins, cardiac glycosides, and some alkaloids.

 For the synthesis of Bile Salts that are important in lipid
digestion and absorption.
 For the synthesis of Steroid Hormones that are
biologically important like the sex hormones estrogen and
progesterone.
 For the synthesis of vitamin D3
 As a structural material in Biological Membranes.
 As a component of Lipoproteins as transport of lipid
Cholesterol is important in many ways:

Metabolism of dietary lipids
Digestion, and Absorption

In infants :
 Digestion begins in stomach catalyzed by the acid-
stable lingual lipase from glands at the back of the
tongue.
 It digests short or medium chain fatty acids such as
those found in milk fat
 However, the rate of hydrolysis is slow because the
lipid is not yet emulsified.
1st Processing In Stomach

 These TAG molecules can be degraded by a separate
gastric acid lipase. This enzyme is active only at neutral PH
Therefore, of little use in the adult stomach where, the ph is
low, but is active In neonates whose stomach PH is nearer to
neutrality and whose diets contain mainly milk lipids.
 Overall in adults dietary lipids are not digested to any
extent in the mouth or the stomach but rather progress more
or less intact to the small intestine.

2nd Emulsification in the small intestine
 Emulsification of dietary lipids in the small intestine
(duodenum)
 Emulsification increases the surface area of the
hydrophobic lipid droplets so that the digestive act
effectively.
 Emulsification is accomplished by two mechanisms
namely:
 The use of the detergent ( amphipathic ) surface
active properties of bile salts synthesized in the liver
and stored in the gall bladder and

First step in processing dietary fats is emulsification.
 Emulsification breaks lipid droplets into smaller-sized
structures, which increases their overall surface area.
 This process involves mixing (peristalsis) in the duodenum
with bile salts, act like detergents to dissolve lipid droplets.
The increased contact area between water and lipids
facilitates interaction with digestive enzymes.

By Several Pancreatic Lipases,
 TAG hydrolyzed by Pancreatic Lipase at 1 and 3 C.
 Into two types of product: free fatty acids (FFAs) and
2-monoacylglycerols.
 The drug orlistat inhibits lipases and thereby prevents
uptake of many fats as a means of treating obesity in
conjunction with a low-calorie diet.
 Phospholipids are hydrolyzed by phospholipases,
which remove a fatty acid from carbon 2, and which
may be further processed or absorbed.
3rd Degradation by pancreatic enzymes

Overview of lipid digestion

Hormonal Control of lipid digestion
Cholecystokinin
 site of release : from jejunum and lower duodenum
In response to lipids and partially digested proteins
entering small intestines.
 Actions ;
-Gall bladder-- contraction and release of bile
- Pancreatic cells -- release of digestive enzymes
- Decreases Gastricmotility

Secretin
 site –released from other intestinal cells
- In response to low pH of chyme
 Actions;
- Release of a watery solution by pancreas
and liver highin bicarbonate--appropriate
pHfor action of pancreatic enzymes.

Hormonal control of lipid digestion

By micelles formation.
 Mixed micelles = Bile salts, together with free fatty
acids, free cholesterol and 2-monoacylglycerol form
clusters of amphipathic lipids that coalesce with their
hydrophobic groups inside and hydrophilic groups on the
outside of the cluster, and which are soluble in the aqueous
environment of the intestinal lumen.
4th Absorption of lipids by intestinal mucosal cells

By micelles formation.
 Short and medium chain-length fatty acids do not require
the assistance of a micelle for absorption by the intestinal
mucosa.

 Mixed micelles are, therefore approach the primary site of
lipid absorption, the brush border membrane (mucosal cell).
Hydrophilic surface of the micelles facilitates the
transport of the hydrophobic lipids to the brush border
membrane where they are absorbed .

 The mixture of lipids absorbed by the enterocytes migrates
to the endoplasmic reticulum where biosynthesis of complex
lipids takes place.
 Fatty acids are first converted into their activated form
by fatty acyl-CoA synthetase (thiokinase) .
 Using the fatty Acyl CoA derivatives, the 2-
monoacylglycerols absorbed by the enterocytes are converted
to TAGs by the enzyme complex, TAG synthase.
5th Resynthesis of TAG and cholesteryl esters

 Note: Virtually all long-chain fatty acids entering
the enterocytes are used in this fashion to form TAGs,
phospholipids, and cholesteryl esters.
 Short- and medium-chain length fatty acids are not
converted to their CoA derivatives Instead, they are
released into the portal circulation,

 Is the loss of > 6g of fat together with fat
soluble vitamins (A,D,E,K) and essential fatty
acids.
6th Lipid malabsorption (Steatorrhea):

Causes of steatorrea:
 Defective Digestion due to deficiency of pancreatic
lipase
as a result of chronic pancreatits,obstruction of
pancreatic
duct by tumors .
Fecal fat is mostly undigested TAGs.

Defective Absorption due to deficiency of bile salts as a
result of bile duct obstruction as in tumors or stones of
the
bile duct.
Fecal fat is in the form of 2-monoacylglycerol.
 Also absorption may be due to defective intestinal
mucosal cells (by surgical removal).

Possible causes of steatorrea

 Assembly of chylomicrons ( lipids are surrounded by
a
thin layer of Protein, Phospholipids And Unesterified
Cholesterol.
 This layer Stabilizes The Particle And Increases Its
Solubility in aqueous solutions.
7th Secretion of lipids from
intestinal mucosal cells.

 Secretion Of Chylomicrons from intestinal mucosal
cells into lymph (after a lipid- rich meal ( gives lymph a
milky
appearance = chyle, then chylomicrons are conveyed to the
thoracic duct, then to the left subclavian vein, where they
enter the blood).

 Significance of Apolipoprotein B- 48 (the major
Apolipoprotein in chylomicrons) ,synthesized in intestinal
mucosal cells.
 If not synthesized, chylomicrons will not be assembled
and
triacylglycerols accumulate in these cells leading to a
genetic
disorder, Congenital a-beta lipoproteinemia.

Assembly & secretion of Chyle by Int. mucosal cells

Use of dietary lipids by the tissues
 TAGs in chylomicrons are broken primarily in the skeletal
muscles and adipose tissue by LPL to glycerol and free
fatty acids.
LPL
Triacylglycerols →→→… + 3 RcooH
 Lipoprotein lipase is found on the luminal surface of
endothelial cells of the capillary beds of the peripheral
tissues.
 Its deficiency in Familial lipoprotein lipase results in
Massive Chylomicronemia.

 Directly enter adjacent muscle cells or adipocytes.
 Alternatively, free fatty acids may be transported by
albumin ,until they are taken by cells.
 Most cells can oxidize fatty acids to obtain energy.
 However, the brain and other nervous tissues,
erythrocytes and the adrenal medulla Can not
 Adipocytes can also re-esterify free-fatty acids to
produce triacylglycerols molecules, which are stored
until the fatty acids are needed .
Fate Of Free-fatty Acids

 Glycerol to glycerol-3- phosphate by the liver for
Glycolysis.
 Fate of Chylomicron remnants are taken up by the liver
where , they are hydrolyzed to their component parts due to
Apolipoprotein E
 Deficiency of Apolipoprotein E, leads to familial
type
III hyperlipoproteinemia which leads to Defective
removal of Chylomicron -remnants from the plasma,
Fate Of Glycerol

Short answer Questions
1.Triacylglycerols are
A. soluble in water B. partiallysoluble in water
C. Insoluble in water D. None
2.What are the components of a triacylglycerols?
3.What are the sources of fattyacids?
4.At whichposition is the fattyacidattached to the cholesterol ring,?
5.which fatty acid should havethe least melting point out of the followings?
Steric acid[0db] Arachidonic acid[4db], Timnodonic acid [5db]
6.Name a fatty acid with18 carbonatoms and a single double bond in trans
configuration
.7. Numbercarbons of cholesterol is -------------------

Solution
1.Insoluble in water
2.Glycerol+3fattyacid
3.Diet, Endogenous synthesis and derivedfromadiposetissue by adipolysis.
4.3rd position
5.Timnodonicacid, since it has five double bonds; more the degree of unsaturation,
lesser is the melting point.
6.Elaidic acid
7.27C