Lipid digestion and absorption for medical school

BIOCHEMISTRY

1. LIPIDS :
DIGESTION AND ABSORPTION
V.S.RAVIKIRAN, MSc.

2. V.S.RAVIKIRAN, MSc.,
Department of Biochemistry,
ASRAM Medical college,
Eluru-534005.AP, India.
[email protected]

4. DIETARY FAT :
- 90% is normally triglycerides.
- Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.
Average Normal Indian Diet: 20-30 gm/day
Western Diet: 2 or 3 times of this

5. Challenges
Lipids are not water soluble
Triglycerides too large to be absorbed
Digestive solution
Triglycerides mix with bile and pancreatic secretions
Emulsification and digestion

6. 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

7. 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

8. 2. Digestion:
Pancreatic juice:
- Pancreatic lipase
- Cholesterol estarase
- Phospholipase A2
- Colipase
Lipolytic enzymes
colipase
lipase
TG particle

9. Hydrolysis of lipids
Triglycerides (TG)
TG + H2O → Diglyceride + fatty acid (FA)
Diglyceride + H2O → Monoglyceride (MG) + FA
2+
2 H2O
lipase
O
O
O
O
R
R
OR
O
OH
O
OH
R
O R
O
O
–
+ 2 H
+

10. Cholesterol esters & phospholipids* (PL)
↓ esterase ↓ phospholipases
FA + cholesterol (chol) FA + lyso PL

In all cases, products are more polar than reactants
O
O
O
P
O
R
OR
O
O
OR
–
** biliary & dietary biliary & dietary

11. Physiologically important lipases
Lipase Site of action Preferred substrateProduct(s)
Lingual / acid stable
lipase
Mouth , stomach TAGS with med
chain FAS
FFA+DAG
Pancreatic lipase +
co-lipase
Small intestine TAGS with long
chain FAS
FFA+2MAG
Intestinal lipase with
bile acids
Small intestine TAGS with med
chain FAS
2FFA+glycerol
Phospholipase A2 +
bile acids
Small intestine PLs with unsat. FA
on position 2
Unsat FFA
lysolecithin
Lipoprotien lipase
insulin (+)
Capillary walls TAGs in chylomicron
or VLDL
FFA+glycerol
Hormone sensitive
lipase
Adipose cell TAG stored in
adipose cells
FFA+glycerol

12. 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

13. Bile salts: synthesis, secretion
 Synthesized in the liver.
cholesterol
Bile acid
Bile acyl-CoA
+ amino acid ( glycine / taurine )
Bile salt

14. Biliary Lipid Secretion
Sinusoidal Membrane
BloodBlood HepatocyteHepatocyte
Canalicular Membrane
Bile SaltBile Salt
ABCG5/G8
Cholesterol
ABCB4
Phospholipid
ABCB11
BileBile

15. Biliary Lipids
Daily Secretion (g)Daily Secretion (g)Lipid ClassLipid Class
Bile salts
Phospholipids
Cholesterol
24
11
2

16. Structure of Biliary and Intestinal Micelles
Cholesterol
Bile Bile
SaltSalt
PhospholipidPhospholipid

17. Biliary Lipid Transport
DuodenumDuodenum
JejunumJejunum
IleumIleum
ColonColon
Biliary
Transport
and
Storage
Liver

18. Fat Digestion
DuodenumDuodenum
JejunumJejunum
IleumIleum
ColonColon
Biliary
Transport
and
Storage
Liver

19. Fat Digestion
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
Fatty Acids +Fatty Acids +
LysophospholipidLysophospholipid
PhospholipidsPhospholipids
I
I
I
TriglyceridesTriglycerides
Fatty Acids +Fatty Acids +
MonoglyceridesMonoglycerides
I
I
II
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
DietaryDietary
Cholesterol esterCholesterol ester
III
I
I
I
Fatty Fatty
acids acids
+ +
cholestecholeste
rolrol

20. Fat Absorption
DuodenumDuodenum
JejunumJejunum
IleumIleum
Biliary
Transport
and
Storage
ColonColon
Liver

21. Absorption from lumen
brush border
membrane
microvillus
diffusion
of micelles
through
unstirred
layer
well-mixed
luminal
contents
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
Absorption
also occurs
via fatty acid
transfer protein
(FATP)
Microvilli
provide very
large absorbing
surface, but
convolutions &
glycocalyx
produce
unstirred layer
Adapted from
Fig. 34 -14 (B & L)
FATP

22. Absorption: role of micelles
Unstirred layer
 200-500 μm thick
Prevents peristaltic
mixing from moving
luminal contents close
to 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

23. LymphLymph EnterocyteEnterocyte
IntestinalIntestinal
LumenLumen
Cholesterol Absorption
Cholesteryl
Ester
ACAT
Cholesterol
II
TT
NPC1L1
ABCG5/
G8

24. LymphLymph EnterocyteEnterocyte IntestinalIntestinal
LumenLumen
Triglyceride Absorption
2 Fatty Acid
+
Monoglyceride
DGAT
Triglyceride
TT
II

25. LymphLymph EnterocyteEnterocyte
IntestinalIntestinal
LumenLumen
Phospholipid Absorption
Phospholipid
Fatty Acid
+
Lysophospholipid
II

26. LymphLymph EnterocyteEnterocyte
IntestinalIntestinal
LumenLumen
Chylomicron Formation
With
apoB48
Cholesteryl
Ester
Triglyceride
Phospholipid

27. 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

28. Formation and secretion of (A) chylomicron in intestinal and

(B) VLDL in Hepatic cell.

29. Packaging for transport
chylomicrons
 Particles for
transport of lipids
to liver &
adipocytes
 Size: 0.1–1 µm
 Average
composition:
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

31. 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

32. Stomach
gastric
mobility
Small
intesti
ne
Dietary
lipids
Degradation of
dietary lipids
cholecytokinin
-
Gut
Endocrine
cells
(enlarged)
+
Secretin
(in blood)
pancreas
+
bicarbonate
s
e
c
r
e
t
e
s
Pancreatic
lipasesecretes
bile
Gall bladder
secretes +
Hormonal control
+

33. triglycerides

34. 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 pancreatitis
Cystic fibrosis
Pancreatic cancer
c) Bile acid deficiency Disease/resection of terminal ileum
Small bowel bacterial over growth.
a) Generalised disorders due to
reduction in absorptive surface area.
Celiac disease
Tropical sprue
b) Specific disorders Hypolactasia
Vit B12 in pernicious anemia
Zn in acrodermatitis enteropathica

35. 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 lymphoma
Primary lymphangiectasia
b) Inherited disorders A-β-lipoprotienemia
Chyluria Chylothorax

36. 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.

37. Summary of lipid digestion
& absorption
TG
MG
FA
MG
FA
(>10C)
FA
(<12C)
chylomicron
BILE
SALTS
chylomicron
mixed
micelle
albumin
BILE
SALTS
FA
lipase-
colipase
lipase-
colipase
apolipoproteins
phospholipids
emulsion
droplet
BILE
SALTS
1818
4ATPs/TG
EnterocyteEnterocyte
oil
drop
TG

38. THE END
THANKS FOR YOUR
ATTENTION