lipid- digestion & absorption
TRANSCRIPT
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DIETARY FAT :- 90% is normally triglycerides.
- Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.
Average Normal Indian Diet: 20-30 gm/dayWestern Diet: 2 or 3 times of this
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Challenges Lipids are not water soluble
Triglycerides too large to be absorbed
Digestive solution
Triglycerides mix with bile and pancreatic secretions
Emulsification and digestion
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IN STOMACH Lingual lipase:
- Active at low ph (pH 2.5 – 5)
- Short chain TGS.
- In milk, butter and ghee.
Gastric lipase:
- Up to 30% of TGS
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IN SMALL INTESTINE
1.Emulisification:
Dispersion of lipids into small droplets
- Bile salts ( detergent action )
Function to transport cholesterol in the digestive system
- Peristalsis ( mechanical mixing )
- phospholipids
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2. Digestion:
Pancreatic juice:
- Pancreatic lipase
- Cholesterol estarase
- Phospholipase A2
- Colipase
Lipolytic enzymes
colipaselipase
TG particle
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Hydrolysis of lipids
Triglycerides (TG)
TG + H2O → Diglyceride + fatty acid (FA)
Diglyceride + H2O → Monoglyceride (MG) + FA
2+
2 H2O
lipase
OO
O
O RR
O R
OOH
OOH
RO R
OO
–
+ 2 H+
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Cholesterol esters & phospholipids* (PL)↓ esterase ↓ phospholipases
FA + cholesterol (chol) FA + lyso PL
In all cases, products are more polar than reactants
OO
O
P OR
O R
OO
OR
–
* biliary & dietary
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Physiologically important lipases
Lipase Site of action Preferred substrate Product(s)
Lingual / acid stablelipase
Mouth , stomach TAGS with medchain FA S
FFA+DAG
Pancreatic lipase +
co-lipase
Small intestine TAGS with long
chain FA SFFA+2MAG
Intestinal lipase withbile acids
Small intestine TAGS with med chainFA S
2FFA+glycerol
Phospholipase A 2 +
bile acids
Small intestine PLs with unsat. FA
on position 2
Unsat FFA
lysolecithin
Lipoprotien lipaseinsulin (+)
Capillary walls TAGs in chylomicronor VLDL
FFA+glycerol
Hormone sensitive
lipase
Adipose cell TAG stored in
adipose cells
FFA+glycerol
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3. Absorption: Bile: Produced in liver, stored in gallbladder
Alkaline solution composed of:
Bile salts
Cholesterol Lecithin
Bilirubin
Bile secretion stimulated by
secretin (target: liver)
CCK (target: liver & gall bladder)
Absorbed bile salts
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Bile salts: synthesis, secretion
Synthesized in the liver.
cholesterol
Bile acid
Bile acyl-CoA
+ amino acid ( glycine / taurine )
Bile salt
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Biliary Lipid Secretion
Sinusoidal Membrane
Blood Hepatocyte
Canalicular Membrane
Bile Salt
ABCG5/G8
Cholesterol
ABCB4Phospholipid
ABCB11
Bile
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Biliary Lipids
Daily Secretion (g)Lipid Class
Bile salts
Phospholipids
Cholesterol
24
11
2
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Structure of Biliary and Intestinal Micelles
Cholesterol
BileSalt
Phospholipid
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Biliary Lipid Transport
Duodenum
Jejunum
Ileum
Colon
BiliaryTransport
andStorage
Liver
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Fat Digestion
Duodenum
Jejunum
Ileum
Colon
BiliaryTransport
and
Storage
Liver
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Fat Digestion
I I
II
III
III II
I
Fatty Acids +
Lysophospholipid
Phospholipids
III
Triglycerides
Fatty Acids +
Monoglycerides
I I
II
III
III
DietaryCholesterol ester
Fattyacids+cholesterol
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Fat Absorption
Duodenum
Jejunum
Ileum
BiliaryTransport
and
Storage
Colon
Liver
Ab ti f l
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Absorption from lumen
brush bordermembrane
microvillus
diffusionof micelles
throughunstirredlayer
well-mixedluminalcontents
monoglycerides
lysophos-pholipids
chol
fatty acids
unstirred layer
cytosol
Movement of lipid digestion products (FA, MG, etc) across mucosal
plasma membrane by simple diffusion of monomers
Absorptionalso occursvia fatty acid transfer protein (FATP)
Microvilliprovide verylarge absorbingsurface, butconvolutions &glycocalyxproduceunstirred layer
Adapted from
Fig. 34
-14 (B & L
)
FATP
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Absorption: role of micelles
Unstirred layer
200-500 μm thick
Prevents peristalticmixing from movingluminal contents closeto cell surface
Crossed by micelle diffusion
because of very low solubility of
lipid molecules & very large distance,
absorption would be very slow
without micelles
Mixed micelles act as:
carriers of lipid monomers (FA, MG, chol, vit. A, D, E, K)
reservoirs: as monomers absorbed, they are rapidly replaced by dissociation
from micelles
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Lymph Enterocyte
Intestinal
Lumen
Cholesterol Absorption
CholesterylEster
ACAT
Cholesterol NPC1L1
ABCG5/
G8
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Lymph Enterocyte IntestinalLumen
Triglyceride Absorption
2 Fatty Acid+
Monoglyceride
DGAT
Triglyceride
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Lymph Enterocyte
IntestinalLumen
Phospholipid Absorption
Phospholipid
Fatty Acid+
Lysophospholipid
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Enterohepatic circulation(bile salt recycling)
Bile salts absorbed
toward end of ileum
Absorption by Na+ – driven cotransport
Na+ – bile salt symport
Carried in portal blood
bound to albumin
Added to bile again by
liver & secreted again
Typically make 3-4
roundtrips during
average meal
cholesterolbile salts
Sherwood, Fig.16-17
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ormation and secretion of (A) chylomicron in intestinal and
(B) VLDL in Hepatic cell.
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Packaging for transport
chylomicrons Particles for
transport of lipids
to liver &
adipocytes
Size: 0.1 – 1 µm
Averagecomposition:
TG (84%)
chol (2%)
cholE (4%)PL (8%) apolipoproteins (2%)
apolipo-proteins
cholE, TG
chol PL
PL
Lehninger et al.,3rd ed., Fig. 17-2
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Fate of dietary lipids:
TGs: FFA + glycerol
FFA:
- FFA from TGs muscle (energy production)
adipocytes( re esterified to TGs)
Glycerol : Glycerol from TGs in liver forms glycerol 3 phosphate ( glycolysis,
gluconeogenesis)
Chylomicron remnants:
Endocytosed into liver and are hydrolysed to their component parts and recycled by
the body.
- If this process is decreased due to impaired binding to the receptor on liver, they
accumulate in the plasma leading to type III hyperlipoproteinemia
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Stomach
gastric mobility
Smallintesti
ne
Dietary lipids
Degradation of dietary lipids
cholecytokinin
-
GutEndocrine
cells(enlarged)
+
Secretin(in blood)
pancreas
+
bicarbonate
Pancreaticlipase
bile
Gall bladder
+
Hormonal control
+
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Abnormalities of maldigestion/malabsorption
The main causes of malabsorption ( STEATORRHEA ) under 3 catagories:
1. Disorders of intraluminal digestion:
2.Disorders of transport into mucosal cells:
a) Altered gastric function Post gastrectomy syndrome
b) Pancreatic insufficiency Chronic pancreatitisCystic fibrosis
Pancreatic cancerc) Bile acid deficiency Disease/resection of terminal ileum
Small bowel bacterial over growth.
a) Generalised disorders due toreduction in absorptive surface area.
Celiac diseaseTropical sprue
b) Specific disorders Hypolactasia Vit B12 in pernicious anemiaZn in acrodermatitis enteropathica
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3. Disorders of transport out of the mucosal cell:
Clinical presentation of the patient suffering from malabsorption /mal digestion
classically includes the following features:
- Evidence of general ill health
- Isolated nutritional deficiencies
- Abdominal symptoms- Watery diarrhea and possibly steatorrhea
a) Blockage of the lymphatics Abdominal lymphomaPrimary lymphangiectasia
b) Inherited disorders A-β-lipoprotienemia
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Tests for assessing fat absorption and malabsorption:1.Fat globules ( fecal microscopy )
2. Mixed chain triglyceride breath test
3. Measurement of fecal fat
Tests for pancreatic function:
Pancreaolauryl test , fecal elastase.
S f li id di ti
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Summary of lipid digestion
& absorption
TGMGFA
MG
FA (>10C)
FA (<12C)
chylomicron
BILESALTS
chylomicron
mixedmicelle
albuminBILESALTS
FA
lipase-
colipase
lipase-colipase
apolipoproteinsphospholipids
emulsiondroplet
BILESALTS
18
4ATPs/TG
Enterocyte
oildrop
TG