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Digestionand Absorption Of
Lipids
Dr. Dnyanesh B. Amle
MD, DNB, CCMTD
Definition
They have the common property
of being
(1) relatively insoluble in water
(2) soluble in nonpolar solvents
such as alcohol, ether and
chloroform.
Functions
• Storage form of energy
– Concentrated storage
– 9.24kcal/g
• Bio membrane
– Structural components
– Phospholipids
– Glycolipids
• Metabolic regulator
– Steroid hormones
– Prostaglandins
• Surfactant
– Diphosphatidylcholine
(Lecithine)
• Detergent,emulsifier
• Electric insulator of
neuron
• Insulator from external
temperature
• Shape and contour to the
body
• Cushioning to internal
organs
• Fat soluble vitamins
• Taste and palatability
Vs
Dietary fatComposition
>More than 95% : TG
Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.
Dietary sources ofLipids
Overview
Digestion in Mouth
TG 1,2 DAG +FFA
Lingual lipase:
Secreted by dorsal surface of tongue
Active at low pH (pH 2.0 – 7-5)
optimum pH 4.0-4.5
Ideal substrate-Short chain TGS
Enzymatic action continues in stomach
Short chain fatty acids: absorbed directly from the
stomach wall
Enter the portal vein.
Lingual lipase
Triglyceridedegradation
Digestion inStomach
Gastric Lipase
• Optimum p H 5.4 (4-7)
• Acid stable
• Gastrin→ Chief cells
• Requires the presence of Ca++
• Short and medium chain fatty acid (30%)
Fats ingastric emptying : Satiety
Fats → Enterogastrone
↓
inhibits gastric motility
↓
↓ rate of emptying of stomach
↓
high satiety value.
Significance of Lingual & GastricLipases
• Neonates
• Pancreatic insufficiency
• Cystic fibrosis
• other pancreatic disorders
• short and medium chain fatty
Emulsification anddigestion
 Lipids
• hydrophobic
• poorly soluble in the aqueous environment
• Lipase, : water soluble
• can only work at the surface of fat globules.
 Digestion is greatly aided by
Emulsification : breaking up of fat globules into
much smaller emulsion droplets.
Emulsification anddigestion
TG digestion :
• occurs at lipid-water interfaces
• Rate α surface area
• increased by
• churning peristaltic movements of the intestine
• emulsifying action of bile salts
• Emulsification takes place in the duodenum.
Digestion in smallintestine
• Major site of fat digestion
• Effective → Pancreatic lipase and bile salts.
• Bile salts → effective emulsifying agents
• Secretion of pancreatic juice is stimulated by?
• acid gastric /Protein rich content in duodenum
• Secretin/ Cholecystokinin Pancreozymin
GI hormones
Secretin- ↑ secretion of electrolytes and HCO3-
rich fluid components of pancreatic juice
Pancreozymin of CCK –
stimulates the secretion of the pancreatic enzymes
Cholecystokinin of CCK-PZ-
Contraction of the gall bladder
Dilatation of spincture of Oddi
Hepatocrinin-
Released by intestinal mucosa
stimulates more bile formation (poor in bile acid)
Contents of PancreaticJuice
Pancreatic Lipase- triglycerides
Phospholipase A2- Phospholipids
Cholesterol esterase- Cholesteryl esters
BileSalts
• Required for the proper functioning of the
pancreatic lipase enzyme
• Combines lipase + 2 X Colipase.
• Enhances the lipase activity
• Emulsification of fats
Colipase
lipase
TG particle
BileSalts
• Synthesized in the liver
• Stored in the gall bladder
• Derivatives of cholesterol
• sterol ring + side chain + glycine / Taurine
• Na & K salts of Glycocholic & Taurocholic acid
• Entero-hepatic circulation
Emulsification by bilesalts
interact with the dietary lipid particles and the aqueous duodenal contents
stabilizing the lipid particles as smaller preventing them from coalescing
TG degradation by pancreaticlipase
• specific for I0 ester linkages
• Cant act on ‘2
• Acts on FA present at position 1 and 3
↓
α,β diglyceride
↓
β mono glyceride
TG degradation by pancreaticlipase
• β- Mono acyl glycerol ---------------→ α- Mono acyl glycerol
• α- Mono acyl glycerol ---------------→ Glycerol + FA
• Primary product
• β- Mono acyl glycerol (78%)
• α- Mono acyl glycerol (6%)
• free fatty acids
• glycerol (14%)
Isomerase
Pancreatic lipase
Emulsification andDigestion of TG
Significance ofPancreatic lipase
• High concentration in pancreas.
• severe pancreatic deficiency such
• cystic fibrosis
• malabsorption of fats
• Orlistat
• antiobesity drug
• inhibits gastric and pancreatic lipases
• decreasing fat digestion and absorption
• weight loss.
Cholesteryl esterdegradation
• Dietary cholesterol
• mainly free (Non esterified) form
• 10-15% is in esterified form
• Hydrolase : activity ↑ by bile salts
Phospholipiddegradation
Absorption ofLipids
Glycerol, short chain FA & medium chain FA
directly absorbed from the intestinal lumen →
portal vein → liver
Long chain fatty acids, free cholesterol and β- acyl glycerol
With bile salts form mixed micelles
Micelles
• Spherical
• Clusters of amphipathic lipids
• hydrophobic groups on the inside
• hydrophilic groups on the outside of clusters
• Mixed micelles : soluble in the aqueous environment of the
intestinal lumen
• Approach the brush border membrane of the enterocytes
Micelles
• Micelles constantly break down and re-form,
• MAG & FA :
• nonpolar
• diffuse across the plasma membrane of the enterocyte.
• Some : specific transport proteins
Clinical Significance of Cholesterol
Absorption
Ezetimibe
• Blocks a protein mediating cholesterol
transport across enterocytes
• Effective at reducing levels of LDL cholesterol
• Clinical trials are in progress
Resynthesis of TAG and CHE
Within the intestinal epithelium
• 1- monoacyglycerols → FA + glycerol
• 2-monoacylglycerols → TAC
(monoacylglycerolpathway)
• Lysophospholipids → phospholipids.
• Cholesterol → Cholesteryl esters
• LCFA → TGs, PL, CHE.
• SCFA & MCFA → portal circulation
• carried by serum albumin to liver.
Formation and Transportationof
Chylomicrons
Lipid Malabsorption (Steatorrhea)
• lipids loss (including fat soluble vitamins A,D E
and K) in the feces.
• Cause
• pancreatic insufficiency
• cystic fibrosis
• chronic diseases of pancreas
• surgical removal of pancreas
• Shortened bowel, Celiac diseases, sprue or
crohn’s disease
• Bile duct obstruction
• Milk and coconut oil are used therapeutically
since they contain medium chain fatty acids.
Secretion of lipidsfrom enterocytes
• Once inside the enterocyte
• monoglycerides and fatty acids → TAG.
• TAG + CH & Fat soluble vitamins → chylomicrons.
• Chylomicrons are lipoproteins, special particles that
are designed for the transport of lipids in the
circulation.
• Chylomicrons are released by exocytosis at the
basolateral surface of the enterocytes.
• too large to enter typical capillaries.
• enter lacteals
• Chylomicrons then flow into the circulation via
lymphatic vessels.
Structure ofChylomicron
 Size: 0.1–1 µm
 Average
composition
o TG (84%)
o Cholesterol(2%)
o Ester Cholesterol
(4%)
o Phospholipid (8%)
o Apo lipoproteins (2%)
Transport and Utilizationof chylomicrons
Clinical significance ofChylomicron
synthesis andutilization
• Defective synthesis- Deficiency of apo-B 48 protein.
• The triglyceride may accumulate in intestinal cells.
• Chyluria- abnormal connection between urinary tract and
lymphatic drainage system of the intestines
• forming Chylous fistula
• passage of Milky urine.
• Chylothorax- Small intestine resulting in accumulation of lymph
in pleural cavity giving Milky pleural effusion
Physiologically importantlipases
Lingual / acid
stable lipase
Mouth , stomach TAGS with
medium chain
FAS
FFA+DAG
Pancreatic lipase
+ co-lipase
Small intestine TAGS with long
chain FAS
FFA+2MAG
Intestinal lipase
with bileacids
Small intestine TAGS with
mediumchain
FAS
2FFA+glycerol
PhospholipaseA2
+ bileacids
Small intestine PLs with unsat.
FAat position2
Unsat FFA
lysolecithin
Lipoprotein
lipase insulin (+)
Capillarywalls TAGs in
chylomicronor
VLDL
FFA+ glycerol
Hormone
sensitive lipase
Adiposecell TAG stored in
adiposecells
FFA+ glycerol
Summary oflipid digestion and
Absorption
Chylomicrons deliver absorbed TAG to the body's cells. TAG
in chylomicrons and other lipoproteins are hydrolyzed
by lipoprotein lipase, an enzyme that is found in capillary
endothelial cells. Monoglycerides and fatty acids released
from
digestion of TAG then diffuse into cells.
Digestion and absorption of lipids

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Digestion and absorption of lipids

  • 1. Digestionand Absorption Of Lipids Dr. Dnyanesh B. Amle MD, DNB, CCMTD
  • 2. Definition They have the common property of being (1) relatively insoluble in water (2) soluble in nonpolar solvents such as alcohol, ether and chloroform.
  • 3. Functions • Storage form of energy – Concentrated storage – 9.24kcal/g • Bio membrane – Structural components – Phospholipids – Glycolipids
  • 4. • Metabolic regulator – Steroid hormones – Prostaglandins • Surfactant – Diphosphatidylcholine (Lecithine) • Detergent,emulsifier
  • 5. • Electric insulator of neuron • Insulator from external temperature • Shape and contour to the body
  • 6. • Cushioning to internal organs • Fat soluble vitamins • Taste and palatability Vs
  • 7. Dietary fatComposition >More than 95% : TG Cholesterol, Cholesteryl esters, Phospholipids, and Unesterified fatty acids.
  • 10. Digestion in Mouth TG 1,2 DAG +FFA Lingual lipase: Secreted by dorsal surface of tongue Active at low pH (pH 2.0 – 7-5) optimum pH 4.0-4.5 Ideal substrate-Short chain TGS Enzymatic action continues in stomach Short chain fatty acids: absorbed directly from the stomach wall Enter the portal vein. Lingual lipase
  • 12. Digestion inStomach Gastric Lipase • Optimum p H 5.4 (4-7) • Acid stable • Gastrin→ Chief cells • Requires the presence of Ca++ • Short and medium chain fatty acid (30%)
  • 13. Fats ingastric emptying : Satiety Fats → Enterogastrone ↓ inhibits gastric motility ↓ ↓ rate of emptying of stomach ↓ high satiety value.
  • 14. Significance of Lingual & GastricLipases • Neonates • Pancreatic insufficiency • Cystic fibrosis • other pancreatic disorders • short and medium chain fatty
  • 15. Emulsification anddigestion  Lipids • hydrophobic • poorly soluble in the aqueous environment • Lipase, : water soluble • can only work at the surface of fat globules.  Digestion is greatly aided by Emulsification : breaking up of fat globules into much smaller emulsion droplets.
  • 16. Emulsification anddigestion TG digestion : • occurs at lipid-water interfaces • Rate α surface area • increased by • churning peristaltic movements of the intestine • emulsifying action of bile salts • Emulsification takes place in the duodenum.
  • 17. Digestion in smallintestine • Major site of fat digestion • Effective → Pancreatic lipase and bile salts. • Bile salts → effective emulsifying agents • Secretion of pancreatic juice is stimulated by? • acid gastric /Protein rich content in duodenum • Secretin/ Cholecystokinin Pancreozymin
  • 18. GI hormones Secretin- ↑ secretion of electrolytes and HCO3- rich fluid components of pancreatic juice Pancreozymin of CCK – stimulates the secretion of the pancreatic enzymes Cholecystokinin of CCK-PZ- Contraction of the gall bladder Dilatation of spincture of Oddi Hepatocrinin- Released by intestinal mucosa stimulates more bile formation (poor in bile acid)
  • 19. Contents of PancreaticJuice Pancreatic Lipase- triglycerides Phospholipase A2- Phospholipids Cholesterol esterase- Cholesteryl esters
  • 20. BileSalts • Required for the proper functioning of the pancreatic lipase enzyme • Combines lipase + 2 X Colipase. • Enhances the lipase activity • Emulsification of fats Colipase lipase TG particle
  • 21. BileSalts • Synthesized in the liver • Stored in the gall bladder • Derivatives of cholesterol • sterol ring + side chain + glycine / Taurine • Na & K salts of Glycocholic & Taurocholic acid • Entero-hepatic circulation
  • 22. Emulsification by bilesalts interact with the dietary lipid particles and the aqueous duodenal contents stabilizing the lipid particles as smaller preventing them from coalescing
  • 23. TG degradation by pancreaticlipase • specific for I0 ester linkages • Cant act on ‘2 • Acts on FA present at position 1 and 3 ↓ α,β diglyceride ↓ β mono glyceride
  • 24. TG degradation by pancreaticlipase • β- Mono acyl glycerol ---------------→ α- Mono acyl glycerol • α- Mono acyl glycerol ---------------→ Glycerol + FA • Primary product • β- Mono acyl glycerol (78%) • α- Mono acyl glycerol (6%) • free fatty acids • glycerol (14%) Isomerase Pancreatic lipase
  • 26. Significance ofPancreatic lipase • High concentration in pancreas. • severe pancreatic deficiency such • cystic fibrosis • malabsorption of fats • Orlistat • antiobesity drug • inhibits gastric and pancreatic lipases • decreasing fat digestion and absorption • weight loss.
  • 27. Cholesteryl esterdegradation • Dietary cholesterol • mainly free (Non esterified) form • 10-15% is in esterified form • Hydrolase : activity ↑ by bile salts
  • 29. Absorption ofLipids Glycerol, short chain FA & medium chain FA directly absorbed from the intestinal lumen → portal vein → liver Long chain fatty acids, free cholesterol and β- acyl glycerol With bile salts form mixed micelles
  • 30. Micelles • Spherical • Clusters of amphipathic lipids • hydrophobic groups on the inside • hydrophilic groups on the outside of clusters • Mixed micelles : soluble in the aqueous environment of the intestinal lumen • Approach the brush border membrane of the enterocytes
  • 31. Micelles • Micelles constantly break down and re-form, • MAG & FA : • nonpolar • diffuse across the plasma membrane of the enterocyte. • Some : specific transport proteins
  • 32. Clinical Significance of Cholesterol Absorption Ezetimibe • Blocks a protein mediating cholesterol transport across enterocytes • Effective at reducing levels of LDL cholesterol • Clinical trials are in progress
  • 33. Resynthesis of TAG and CHE Within the intestinal epithelium • 1- monoacyglycerols → FA + glycerol • 2-monoacylglycerols → TAC (monoacylglycerolpathway) • Lysophospholipids → phospholipids. • Cholesterol → Cholesteryl esters • LCFA → TGs, PL, CHE. • SCFA & MCFA → portal circulation • carried by serum albumin to liver.
  • 35. Lipid Malabsorption (Steatorrhea) • lipids loss (including fat soluble vitamins A,D E and K) in the feces. • Cause • pancreatic insufficiency • cystic fibrosis • chronic diseases of pancreas • surgical removal of pancreas • Shortened bowel, Celiac diseases, sprue or crohn’s disease • Bile duct obstruction • Milk and coconut oil are used therapeutically since they contain medium chain fatty acids.
  • 36. Secretion of lipidsfrom enterocytes • Once inside the enterocyte • monoglycerides and fatty acids → TAG. • TAG + CH & Fat soluble vitamins → chylomicrons. • Chylomicrons are lipoproteins, special particles that are designed for the transport of lipids in the circulation. • Chylomicrons are released by exocytosis at the basolateral surface of the enterocytes. • too large to enter typical capillaries. • enter lacteals • Chylomicrons then flow into the circulation via lymphatic vessels.
  • 37. Structure ofChylomicron  Size: 0.1–1 µm  Average composition o TG (84%) o Cholesterol(2%) o Ester Cholesterol (4%) o Phospholipid (8%) o Apo lipoproteins (2%)
  • 39. Clinical significance ofChylomicron synthesis andutilization • Defective synthesis- Deficiency of apo-B 48 protein. • The triglyceride may accumulate in intestinal cells. • Chyluria- abnormal connection between urinary tract and lymphatic drainage system of the intestines • forming Chylous fistula • passage of Milky urine. • Chylothorax- Small intestine resulting in accumulation of lymph in pleural cavity giving Milky pleural effusion
  • 40.
  • 41. Physiologically importantlipases Lingual / acid stable lipase Mouth , stomach TAGS with medium chain FAS FFA+DAG Pancreatic lipase + co-lipase Small intestine TAGS with long chain FAS FFA+2MAG Intestinal lipase with bileacids Small intestine TAGS with mediumchain FAS 2FFA+glycerol PhospholipaseA2 + bileacids Small intestine PLs with unsat. FAat position2 Unsat FFA lysolecithin Lipoprotein lipase insulin (+) Capillarywalls TAGs in chylomicronor VLDL FFA+ glycerol Hormone sensitive lipase Adiposecell TAG stored in adiposecells FFA+ glycerol
  • 42. Summary oflipid digestion and Absorption Chylomicrons deliver absorbed TAG to the body's cells. TAG in chylomicrons and other lipoproteins are hydrolyzed by lipoprotein lipase, an enzyme that is found in capillary endothelial cells. Monoglycerides and fatty acids released from digestion of TAG then diffuse into cells.