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1/5/2024

Major steps of the digestion of dietary lipid:


I. Processing of dietary lipid in stomach:
 Fat (triacylglycerol) digestion begins in stomach to a
limited extent by lingual lipase and gastric lipase but
the extreme acidic pH of stomach is not suitable for
Lipid digestion and absorption their activity.
 Both enzymes mainly act on TAG containing short or
medium chain fatty acid (<12 carbon such as found in
milk fat).
Lingual lipase
Or
Gastric lipase
Fat (triacylglycerol) Fatty acids +
1,2-diacylglycerols

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Remember,
 Lingual lipase is secreted by Ebner’s gland on the dorsal
An adult ingests about 60-150 gm lipids/day, of which
more than 90% is TAG (Triacylglycerol). surface of the tongue. Gastric lipase is secreted from
gastric mucosa. In spite of limitations, lingual lipase and
The dietary lipids are:
gastric lipase digested around 30% of TAG.
- Triacylglycerol (TAG)- 90%
 The rate of digestion is slow by them because fat is not
- Free cholesterol yet emulsified.
- Cholesteryl ester  In case of infants, the milk fat (with short chain fatty
- Phospholipid & acids) can be hydrolyzed by gastric lipase & lingual
- Free fatty acid lipase to some extent. This is because, the stomach PH
of infants is close to neutrality, ideal for action.
 These lipases are specially important for fat digestion in
patients with pancreatic insufficiency (eg.-cystic fibrosis)
with near or complete absence of pancreatic lipase.

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Phospholipid II. In intestine:


TAG
A. Emulsification of dietary fat in duodenum:
 It is the process by which large fat or oil globules are
broken down into smaller fine particles. It increases the
surface area of fat. So water soluble lipase enzymes can
work effectively over wider surface of fat. It occurs in
duodenum.
Cholesteryl ester  Emulsification of fat is done by two complementary
mechanisms:
a. Reduction of surface tension of fat droplets by bile
Cholesterol
salts and lecithin of bile.
b. Mechanical mixing by peristaltic movement of
intestine.

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 Some of the 2-monoacylglycerol isomerizes to 1-MAG


which is then digested by pancreatic lipase to fatty acid
and glycerol. In this process about 25-30% TAG is
completely digested to fatty acid and glycerol.
isomerization
2-MAG 1-MAG
Colipase Pancreatic lipase

Fatty acid + glycerol

 So, the end products of TAG digestion are-


2-monoacylglycerol, free fatty acid and glycerol.

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Remember,
 Bile salt and lecithin are amphipathic whose polar part are
highly water soluble and apolar part are soluble in lipid. Remember,
 The polar projections which are soluble in water greatly  Colipase, a protein secreted in the pancreatic juice, is
reduced the surface tension of fat and makes it soluble as secreted as the zymogen pro-colipase which is
well. activated in the intestine by trypsin.
 Thus bile salt and lecithin make the fat globules  Colipase binds to the –COOH terminal domain of the
fragmented by agitation with water in the small intestine.
pancreatic lipase and exposes its active site for
 Agitation decreases the diameter of fat globules to less
lipolytic action.
than 1 µm which increases the total surface area of fat
about 1000 fold.
 Water soluble lipase enzyme can attack the fat globules
only on their surface.

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B. Degradation of dietary lipids by pancreatic enzymes:


ii. Dietary cholesterol degradation-
The dietary TAG, cholesteryl ester and phospholipid
are degraded by pancreatic enzymes which secretion is  Most dietary cholesterol is present in free form
hormonally controlled. with only 10-15% in ester form.
i. TAG degradation-  Dietary cholesterol ester is digested by pancreatic
 Pancreatic lipase with the help of colipase removes cholesterol esterase to fatty acid and free
the fatty acid at carbon 1 and 3 of TAG and cholesterol. Bile salts enhance the cholesterol
produces 2-monoacylglycerol (2-MAG) and free esterase activity.
fatty acid (FFA). Cholesterol esterase
Cholesterol ester Cholesterol +
Pancreatic lipase Fatty acid
TAG 2-monoacylglycerol + FFA
Colipase

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iii. Dietary phospholipid degradation- So, end products of lipid digestion are-
 Dietary phospholipid is digested by pancreatic • Free fatty acids
phospholipase A2 removing fatty acid from 2nd • Glycerol
carbon of glycerol moiety and produces • 2-MAG
lysophospholipid. Bile salts enhance the activity of • Cholesterol
this enzyme. • Lysophospholipid

pancreatic phospholipase A2
Phospholipid lysophospholipid + - All of them are amphipathic in nature having
Fatty acid hydrophobic and hydrophilic group.

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Digestion of Lipid: (in short) Absorption of lipid:


a. In stomach: I. Short & medium chain fatty acid (< 10-12 carbon atom)
Lingual lipase
and glycerol absorption:
Or
Gastric lipase  Directly absorbed to portal blood by simple diffusion
Fat (triacylglycerol) Fatty acids +
and are transported to liver in a bound form with
1,2-diacylglycerols
albumin.
II. Long chain fatty acid (>12 carbon atom) , cholesterol, 2-
b. In intestine:
MAG and lysophospholipid absorption:
Bile salts a. Formation and ferrying function of micelle:
Large Fat globule Small Fat molecule
Lecithin
(Emulsification)  They can not reach the surface of intestinal mucosal
cells as they are relatively water insoluble.

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 These products together interact with 20-40 molecules


TAG
Pancreatic lipase
2-monoacylglycerol + FFA of bile salts of bile to form globular water soluble small
Colipase spherical or cylindrical globular aggregates called
micelle.
 Micelle is water soluble because their hydrophobic
isomerization parts are pushed interior and hydrophilic parts are
2-MAG 1-MAG exposed exterior.
Colipase Pancreatic lipase
Fatty acid + glycerol

Cholesterol esterase
Cholesterol Ester Cholesterol + FFA

Pancreatic phospholipase A2
Phospholipids Lysophospholipids +
FFA
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 TAG and cholesterol ester are then coated with a


protein named apoprotein B-48, cholesterol and
phospholipid to form chylomicron.
 Chylomicron are released by exocytosis from enterocytes
into the lymphatic vessels.
 They follow the lymphatic system to the thoracic duct
and are then conveyed to the left subclavian vein where
they enter the blood.
Remember,
Fat absorption is maximum in upper small intestine and
minimum in ileum.

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 Now with micelle, the products of lipid digestion moves Fate of absorbed lipids in the intestinal mucosal cells
through the aqueous media of intestinal lumen and
reach the brush border of intestinal mucosal cells.
 The membrane of brush border of intestinal mucosal
cells is separated from the liquid contents of the
intestinal lumen by an unstirred water layer.
 Micelles facilitates the transport of hydrophobic lipid
through the unstirred water layer to the intestinal
mucosal cells.
 From mucosal cells lipids are absorbed to enterocytes by
simple diffusion.
 After absorption of lipids, bile salts come back to lumen
to form micelle again and repeat the same process.
 This function of bile salt is called ferrying function in
absorption of lipids.

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b. Fate of absorbed lipids in the intestinal mucosal cells: Absorption of lipid: in short
 Long chain fatty acid (>12 carbon) are reesterified to
TAG in the enterocytes. 1. Short Chain FA & Vit- A, D, E, K
(Within the enterocyte glucose provides glycerol 3-
phosphate which is acylated by absorbed fatty acid to From intestinal lumen
produce TAG via phosphatidic acid pathway.) by simple diffusion
 2-MAG is again acylated (addition of fatty acid) to Intestinal mucosal cells
TAG through monoacylglycerol pathway. by simple diffusion
 Lysophospholipid and most of the cholesterol are Portal Circulation
esterified to phospholipid and cholesterol ester
respectively. Liver

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2.
2-monoacyl glycerol + Long chain fatty acid +
Cholesterol + Lysophospholipid + Bile Salts
• Co-transport
Micelle formation and ferrying action of it – It is a carrier mediated energy requiring process
Intestinal brush Border where glucose is coupled to Na+ to be
transported against their concentration gradient.
simple diffusion
– It is found in intestinal epithelial cells, renal
Intestinal mucosal cells tubules, choroid plexus.
Different fate of absorbed lipids within the enterocytes
Formation of chylomicron
lymphatics
via thoracic duct enters into systemic circulation
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Abnormalities of lipid digestion and absorption:


Steatorrhea:
Definition: Excess fecal loss of lipids more than 5-7 g/day. Glucose transporters in mammals
Cause – Impaired digestion and absorption of fat due to-
1. Lipase deficiency a. Na+- glucose cotransport:
2. Lack of alkaline secretion from pancreas.
Type Function Major site
3. Defective reabsorption of bile salts from ileum
These may occur due to - SGLT 1 Glucose Small intestine,
1. Disease of pancreas absorption renal tubules
2. Biliary tract obstruction SGLT 2 Glucose Renal tubules
3. Severe liver dysfunction etc. absorption
Effect - 1. Excess passage of loose stool often diarrhoea.
2. Malabsorption of fat soluble vitamins.
Prevention- 1. Treatment of underlying cause 29

2. Fat restriction in diet.


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b. Facilitated diffusion:
Transport of glucose in different cells of body Type Functions Major site
• Facilitated transport: GLUT 1 Basal glucose Placenta, BB- barrier,
uptake RBC, kidney, colon etc.
– Glucose is transported by
facilitated diffusion along its GLUT 2 β cell glucose β cell of islets, liver,
concentration gradient, using a sensor intestinal and renal
family of fourteen glucose epithelial
transporter in the cell membrane, GLUT 3 Basal glucose Brain, placenta, kidney
designated GLUT-1 to GLUT-14 uptake
which exhibit tissue specificity. GLUT 4 Insulin stimulated Muscle, adipose tissue
– Example GLUT-4 is abundant is glucose uptake
adipose tissue and skeletal muscles GLUT 5 Fructose Jejunum, sperm
and increased by insulin, whereas transport
GLUT-1 is abundant in RBC 30

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 Apical

 Basolateral

 Basement

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Intestinal permeability

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Transepithelial or transcellular permeability:


• This consists of specific transport of solutes across
the epithelial cells.
• It is predominantly regulated by the activities of
specialized transporters that translocate specific
electrolytes, amino acids, sugars, short chain fatty
acids and other molecules into or out of the cell.
Paracellular permeability:
• It depends on transport through the spaces that
exist between epithelial cells.
• This is the main route of passive flow of water and
solutes across the intestinal epithelium.

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