Dr . N.

Sivaranjani
Asst. Prof

Dr. N.Sivaranjani
• Major dietary lipids are Triacyl glycerol -90%,
Cholesterol
Cholesteryl esters &
Phospholipids

 Indian diet contains about 20-30 g of lipids per

day.

Western diet – 2 or 3times more than this

quantity
Dr. N.Sivaranjani
• Animal foods – Diary products like Milk, Butter,
Ghee, Cheese, Meat , Fish and Eggs

• Plant foods – Vegetable cooking oil – Ground nut

oil, Sunflower , Palm ,Rice bran ,Coconut , Cotton
seed oil.

• Vegetable fat are of better quality compared to

animal fats – high PUFA content.
• Although rich in UFA , chance of deterioration
are low because of presence of Antioxidants in
them. Dr. N.Sivaranjani
 Ingestion of fatty food

+ Enterogastrone (CCK & Secretin) from duodenum

•_ Gastric motility & retards discharge of food bolus

This Delays the rate of emptying of stomach

• Fatty food have the ability to satisfy hunger.

Alcohol intoxication can be avoided if consumed after

ingestion of fatty food. (eg- Milk, Cream)
Dr. N.Sivaranjani
• Lingual lipase –

• Originates from glands at the back of the tongue

• Acts of TAG containing fatty acids of short- or

medium-chain length
• SCFA are present in milk, butter and ghee.
• MCFA – mother’s milk and coconut oil.

• Optimum pH of 2.5-5 - Continues to be active in

the stomach. Dr. N.Sivaranjani
Gastric lipase / Acid stable lipase (pH-5.4)
• secreted by chief cells, the secretion is
stimulated by Gastrin.
• Requires presence of Ca2+
• Up to 30% digestion of TAG occurs in stomach
• Acts only on SCFA- milk, butter, ghee

• Clinical importance :- Lipid digestion in neonates

• Milk fat is the primary source of calories in
neonates.

Dr. N.Sivaranjani
 Human milk contains specific Lipase which is
activated by bile salts in duodenum
• Bile salt activated lipase – completely hydrolyses
TAG of milk fat.

• Premature infants – secretary function of

pancreas is not fully established at birth.
So depends only on these lipases.

In pancreatic insufficiency – SCFA and MCFA

are therapeutically used in malabsorption
syndromes.
Dr. N.Sivaranjani
• phenomenon of dispersion of lipids into smaller
droplets (200-5000nm) due to reduction in the
surface tension

Importance :
• Pre- requisite / essential for digestion of lipids
• Increases the surface area of the hydrophobic
lipid droplets
• Digestive enzymes can act effectively

Dr. N.Sivaranjani
Dr. N.Sivaranjani
 Emulsification is favored by

 Bile salts – detergent action

 Phospholipids – Surfactant action

 Peristalsis - mechanical mixing

Dr. N.Sivaranjani
• Synthesized from cholesterol in the liver as bile
acids.
• At physiological pH, the bile acids are mostly
present as anions.

• Na2+ and K+ salts of Glyco-cholate, Glyco-

Chenodeoxycholate, Tauro-cholate, Tauro-
Chenodeoxycholate.

• They are secreted with bile, into the duodenum.

Dr. N.Sivaranjani
• Most effective biological emulsifying agent

• Helps in digestion and absorption of lipids

Emulsification Micelle formation

• stabilize the smaller particles by preventing

them from coalescing.

Dr. N.Sivaranjani
 Taurine

Dr. N.Sivaranjani
• CCK –
• + sec. of panc. E
+ GB to release Bile
into the duodenum
_ Gastric motility

• Secretin –
• + sec. of HCO3
to provide appropriate pH for
pancreatic enzymes

Dr. N.Sivaranjani
• Pancreatic lipase – TAG
• Cholesterol esterase - Cholesteryl esters
• Phospholipase A2 - Phospholipids

Dr. N.Sivaranjani
• Pancreatic lipase

• Alkaline pH (pH-7.7) is favorable for the action of

pancreatic enzymes
• removes the fatty acids of TAG, at carbons 1 & 3

Importance :
• Cystic fibrosis - Pancreatic insufficiency leads to
Significant Malabsorption of fat

Dr. N.Sivaranjani
 O Co-lipase O
P.lipase
=

=
O CH2-O-C-R1 P.lipase O CH2-O-C-R1 O CH2-OH
=

=
R2-C-O-CH O R2-C-O-CH R2-C-O-CH
=

CH2-O-C-R3 R3-COOH CH2-OH CH2-OH

Diacylglycerol R1-COOH
Triacylglycerol FFA 2-Monoacylglycerol

Isomerization

P. lipase O
CH2-OH

=
CH2-O-C-R2
HO-CH
HO-CH
CH2-OH R2-COOH
CH2-OH
Glycerol 1-Monoacylglycerol
Dr. N.Sivaranjani
The major end products of the digestion of TAG :
2-MAG (78%),
1-MAG (6%),
Glycerol and FFA (14%).

Dr. N.Sivaranjani
 Procolipase
Trypsin
Colipase 5 a.a Enterostatin
Colipase

• secreted by the pancreas as a zymogen

• activated in the intestine by Trypsin
• binds with the lipase at a ratio of 1:1
• Colipase binds at the lipid-aqueous interface
and helps to anchor and stabilize lipase to its
substrate TAG.
• Enterostatin – acts as satiety signal for lipids.

Dr. N.Sivaranjani
Pancreatic Cholesterol ester hydrolase
or Cholesterol esterase

Activity of the enzyme is increased in the

presence of bile salts
Dr. N.Sivaranjani
 O Phospholipase-A2 O
=

=
O CH2-O-C-R1 CH2-O-C-R1
=

R2-C-O-CH HO-CH
CH2-O-P-N-base CH2-O-P-N-base

Glycerophospholipid H2O R2-COOH Lysophospholipid

Fatty acid

requires bile salts for optimum activity

Enzyme is secreted as Zymogen form and activated by

Trypsin

Dr. N.Sivaranjani
 Lysolecithin or

Dr. N.Sivaranjani
• C2 FA-is frequently Arachidonic acid in cell
membrane – synthesis of Eicosinoids

• Lysolecithin - is a detergent and hemolytic agent.

• The Phospholipase-A2 enzyme is present in the venom

of viper snakes.

• In viper poisoning -hemolysis and consequent renal

failure is seen.

Dr. N.Sivaranjani
 Site of action of phospholipases
Phospholipase-A1
Phospholipase-A2 O

=
O CH2-O-C-R1
=

R2-C-O-CH O
CH3
+
CH2-O-P-O-C-C-N-CH3

=
Glycerophospholipid O
CH3
H2 H 2
Phospholipase-C
Phospholipase-D

Dr. N.Sivaranjani
• Micelles are molecular aggregate, having a disk /
spherical shape containing :
Interior (hydrophobic) – 2 MAG, LCFA,
cholesterol & phospholipids (hydrophobic part)
Exterior (hydrophilic) - bile salts and
hydrophilic part of cholesterol and PL.

• SCFA & MCFA do not require the assistance of

mixed micelles for absorption by the intestinal
mucosa.
Dr. N.Sivaranjani
Bile salts are reabsorbed in lower part of SI and return
to the liver by portal vein for resecretion into bile –
Enterohepatic circulation
Dr. N.Sivaranjani
Mixed micelles serve as the major vehicles for
the Absorption of lipids from the intestinal
lumen to the intestinal cells

Essential for the absorption of fat-soluble

vitamins such as vitamin A, D and K.

Dr. N.Sivaranjani
• Digestion – Emulsification
by bile salts,
pancreatic enzymes

• Absorption – by micelle
formation with bile salts

• Post-absorption –
re-esterification inside Transport
Intestinal cells
• Transport – chylomicrons
Dr. N.Sivaranjani
Re-esterification Inside the Intestinal mucosal
Cell
2-MAG

Thiokinase
Long chain
Fatty acids

Cholesterol

Short chain
Fatty acids
& glycerol

Portal circulation Lymphatic system

Carried by Albumin Blood

Dr. N.Sivaranjani
Peripheral tissues
 Interior (hydrophobic) –
2 MAG, LCFA, cholesterol
& Phospholipids

Exterior (hydrophilic) - bile

salts and hydrophilic part
of cholesterol and PL

Chylomicrons composed of:

Triacylglycerols (85-90%)
Cholesterol & ChE (5%)
Phospholipids (7%)
Apolipoprotein-B48 (1-2%)

ApoB48

Dr. N.Sivaranjani
• Lipids that are resynthesized in the intestinal
cells are hydrophobic in nature, so surrounded
by Apolipoproteins (apoA and B-48) and
phospholipids at the exterior to form
Chylomicrons.

• This formation stabilizes the droplets and

increases their solubility.

Dr. N.Sivaranjani
 The chyle (milky fluid) from the intestinal
mucosal cells loaded with chylomicrons are
transported through the lacteals into the
thoracic duct and then emptied into lymph
circulation.

Postprandial Lipemia - The serum may appear

milky after a high fat meal due to the presence
of chylomicrons in circulation.

Normally the lipemia clears within a few hours

by the uptake of chylomicrons by tissues by LPL
(lipoprotein lipase enzyme) .
Dr. N.Sivaranjani
 Lipemia sample

Dr. N.Sivaranjani
• Fate of the Chylomicrons:

• Chylomicrons are the transport form of dietary

triglycerides from intestines

• Adipose tissue - storage

• Muscle and Heart - for their energy needs.

Dr. N.Sivaranjani
• Fate of free fatty acids –
• Carried by Albumin
• Taken by Muscle or Adipocytes,
• Oxidized to produce energy

• Fate of glycerol –
• Taken by liver to produce glycerol 3-phosphate
• Which enters Gluconeogenesis / Glycolysis or
used for TAG / PL synthesis in liver.

Dr. N.Sivaranjani
Abnormalities in lipid digestion &
absorption

Dr. N.Sivaranjani
 Steatorrhoea – Greek word, "stear", means fat

large amount of fat or FA excreted in feces >6g \ day.

Most common cause :

Defective digestion - Pancreatic enzyme deficiency
– pancreatitis \ cystic fibrosis

Defective absorption – Celiac disease, Surgical

removal of intestine, Bile salt deficiency – liver
disease \ obstruction in bile duct due to gall stones or Ca head
of pancreas.
Defective chylomicron synthesis – congenital
abetalipoproteinemia Dr.– N.Sivaranjani
defect in ApoLP synthesis.
 In pancreatic deficiency:
unsplit fat is present in
stools.

When bile is not available -

Absorption is defective;
split fat is present in stools;
defective absorption of
vitamin K leads to prolonged
prothrombin time.

Dr. N.Sivaranjani
 Steatorrhea – Rx

Pancreatin / Enzyme Supplements -Trypsin + Lipase

Dr. N.Sivaranjani
• Chyluria - Abnormal connection b/w urinary tract
& lymphatic drainage system of intestine.
• Urine appears milky due to lipid droplets.

• Chylothorax - Abnormal connection b/w the pleural

cavity and thoracic duct - Milky pleural effusion.

Dr. N.Sivaranjani
 Drugs used in Obesity

• Orlistat is a powerful inhibitor of pancreatic

lipase,hence prevents fat digestion and absorption.

• Olestra is a synthetic lipid, produced by

esterification of natural fatty acids with sucrose
(instead of glycerol).
Olestra tastes like a natural lipid.
However, it cannot be hydrolysed and therefore,
gets excreted.
Dr. N.Sivaranjani
 Gall stones
Supersaturation of cholesterol in bile

Due to high conc. of cholesterol to PL & Bile Salts

Cholesterol crystallise out

Gall stones

Small GS – no complication
- pass easily from CBD into intestine
Large GS – block opening of GB or CBD
- inhibits secretion of bile
- impaired dig & abs of fats
- bilirubin accumulate
- jaundice

Treatment
- Chenodeoxycholic acid – dissolve Gall Stones
- Removal of inflamed GB / stones
Dr. N.Sivaranjani
Dr. N.Sivaranjani
Dr. N.Sivaranjani
 Steps of lipid digestion and absorption
Step Location Enzymes
1. Minor digestion
Mouth and stomach lingual/ gastric lipase
(TAGs  DAGs + FFA)
Bile salts, PL,
2. Emulsification Duodenum
Peristalsis
3. Major digestion Pancreatic lipase
TAG  MAG + 2FFA (PL) lumen of the small (+colipase)
CE  chol. + ester (CE) intestines Cholesterol esterase
PL  FA + lysoPL (PLA) Phospholipase A2
4. Formation of mixed
lumen of the small Bile salts , 2MAG,
micelles and passive
intestines PL, chE
absorption
Intestinal epithelial
5. Re synthesis of lipids
cell
6. Assembly and export from Intestinal cells Apolipoproteins and
of chylomicrons to the Lymphatics TAG, chE, PL
Dr. N.Sivaranjani
 Important lipases for digestion of lipids

Lipases Site of action Preferred Products

substrate

Lingual lipase Mouth TAGs with SCFA FFA + DAG

Gastric lipase Stomach / MCFA

Pancreatic lipase Small intestine TAGs with LCFA FFA + 2MAG

+ colipase

Intestinal lipase Small intestine TAGs with 3 FFA+ glycerol

with bile acids MCFA

Phospholipase Small intestine PLs with PUFA LysoPL + FFA

A2 + bile acids at 2nd C

Dr. N.Sivaranjani
Dr. N.Sivaranjani