describes the sources of lipids. enzymes and stages of digestion in detail. absorption form , transport form and disorders of digestion & absorption included.
HỌC TỐT TIẾNG ANH 11 THEO CHƯƠNG TRÌNH GLOBAL SUCCESS ĐÁP ÁN CHI TIẾT - CẢ NĂ...
Dig and abs of lipids
1. Dr . N. Sivaranjani
Asst. Prof
Dr. N.Sivaranjani
2. • 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
3. • 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
4. 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
5. • 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
6. 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
7. 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
8. • 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
10. Emulsification is favored by
Bile salts – detergent action
Phospholipids – Surfactant action
Peristalsis - mechanical mixing
Dr. N.Sivaranjani
11. • 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
12. • Most effective biological emulsifying agent
• Helps in digestion and absorption of lipids
• stabilize the smaller particles by preventing
them from coalescing.
Emulsification Micelle formation
Dr. N.Sivaranjani
14. • 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
15. • Pancreatic lipase – TAG
• Cholesterol esterase - Cholesteryl esters
• Phospholipase A2 - Phospholipids
Dr. N.Sivaranjani
16. • 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
18. The major end products of the digestion of TAG :
2-MAG (78%),
1-MAG (6%),
Glycerol and FFA (14%).
Dr. N.Sivaranjani
19. 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.
Procolipase
Colipase
5 a.a Enterostatin
Trypsin
Dr. N.Sivaranjani
20. Activity of the enzyme is increased in the
presence of bile salts
Pancreatic Cholesterol ester hydrolase
or Cholesterol esterase
Dr. N.Sivaranjani
23. • 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
25. • 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
26. 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
27. 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
28. • Digestion – Emulsification
by bile salts,
pancreatic enzymes
• Absorption – by micelle
formation with bile salts
• Post-absorption –
re-esterification inside
Intestinal cells
• Transport – chylomicrons
Transport
Dr. N.Sivaranjani
29. Long chain
Fatty acids
2-MAG
Cholesterol
Short chain
Fatty acids
& glycerol
Portal circulation Lymphatic system
Blood
Peripheral tissues
Thiokinase
Carried by Albumin
Re-esterification Inside the Intestinal mucosal
Cell
Dr. N.Sivaranjani
30. 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
31. • 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
32. 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
34. • 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
35. • 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
37. 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 – defect in ApoLP synthesis.Dr. N.Sivaranjani
38. 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
40. • 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
41. 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
42. 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 / stonesDr. N.Sivaranjani
45. Steps of lipid digestion and absorption
Step Location Enzymes
1. Minor digestion
(TAGs DAGs + FFA)
Mouth and stomach lingual/ gastric lipase
2. Emulsification Duodenum
Bile salts, PL,
Peristalsis
3. Major digestion
TAG MAG + 2FFA (PL)
CE chol. + ester (CE)
PL FA + lysoPL (PLA)
lumen of the small
intestines
Pancreatic lipase
(+colipase)
Cholesterol esterase
Phospholipase A2
4. Formation of mixed
micelles and passive
absorption
lumen of the small
intestines
Bile salts , 2MAG,
PL, chE
5. Re synthesis of lipids
Intestinal epithelial
cell
6. Assembly and export
of chylomicrons
from Intestinal cells
to the Lymphatics
Apolipoproteins and
TAG, chE, PL
Dr. N.Sivaranjani
46. Lipases Site of action Preferred
substrate
Products
Lingual lipase
Gastric lipase
Mouth
Stomach
TAGs with SCFA
/ MCFA
FFA + DAG
Pancreatic lipase
+ colipase
Small intestine TAGs with LCFA FFA + 2MAG
Intestinal lipase
with bile acids
Small intestine TAGs with
MCFA
3 FFA+ glycerol
Phospholipase
A2 + bile acids
Small intestine PLs with PUFA
at 2nd C
LysoPL + FFA
Important lipases for digestion of lipids
Dr. N.Sivaranjani