1. Digestion of Dietary Lipids

2. Objectives of the Lecture
Understanding the overall process of dietary lipids digestion, the organs involved, the enzymes required and the end products.
Recognizing the biochemical explanation for the clinical manifestations of diseases that involve defective lipids digestion and/or absorption

3. Digestion of Dietary Lipids
Adult ingestion of lipids per day is about grams Components of dietary lipids: 90% Triacylglycerol (TAG) 10% Phospholipids (PL) Cholesterol (C) Cholesterol esters (CE) Free fatty acids (FFA) with fat soluble vitamins Stages of Digestion of Dietary Lipids In mouth (limited) In stomach 3- In small intestine : Emulsification of lipids (by bile acids & peristalsis) Degradation of lipids by pancreatic enzymes

4. Digestion of lipids In the Mouth & Stomach
Lingual lipase: secreted by glands at the back of the tongue.
Gastric lipase: secreted by gastric mucosa
Both enzymes are relatively stable of pH 4-6 (so they are called acid lipases)
Their primary target is triacylglycerol (TAG) containing less than 12 carbon fatty acids i.e. short or medium chain length fatty acids (found in milk fat)
These two enzymes are particularly important in:
- Neonates whose milk fat is the primary source of calories
Patients with pancreatic insufficiency as in cystic fibrosis (with absence of
pancreatic lipase)

5. Emulsification of Dietary Lipids in the Small Intestine
Emulsification increase of the surface area of the hydrophobic lipid droplets so that the digestive enzymes can act effectively
Emulsification is performed by two complementary mechanisms:
1- Detergent property of bile salts
2- Mechanical mixing due to peristalsis
Bile salts are made in the liver & stored in the gall bladder
Bile salts interact with the dietary lipid & the aqueous duodenal contents thus stabilizing the particles & preventing them from coalescing

6. Bile salts are made in the liver & stored in the gall bladder
Bile salts interact with the dietary lipid & the aqueous duodenal contents thus stabilizing the particles & preventing them from coalescing

7. Degradation of Dietary Lipids by Pancreatic Enzymes
The dietary lipids are enzymically degraded by pancreatic enzymes , whose secretion is hormonally controlled

8. Triacylglycerol (TAG) Degradation
Pancreatic lipase
is found in high concentration in pancreatic secretion
Acts on TAG by removing fatty acids at carbon 1 & 3 forming 2-monoacylglycerol & two FAs
Only severe pancreatic deficiency as cystic fibrosis results in maldigestion malabsorption of fat
Colipase
Secreted in 1:1 ratio, as zymogen [ procolipase] by pancreas activated in intestine by trypsin
Anchors the lipase at lipid aqueous interface
Orlistat an antiobesity drug , inhibits gastric & pancreatic lipases causing decreased fat digestion & hence absorption resulting in weight loss

9. Phospholipid (PL) Degradation
PL are degraded at the position 2 by pancreatic phospholipase A2 releasing a free fatty acid & lysophospholipid.
Phospholipase A2 is secreted
as proenzyme, activated by trypsin & requires bile salts for optimum activity
This is followed by removal of
fatty acids at position 1 of lysophospholipid by the action of lysophospholipase leaving glycerylphosphoryl base

10. Cholesteryl Ester (CE) Degradation
15-20% of dietary cholesterol is esterified
Cholesterol ester hydrolase (cholesterol esterase) activity is greatly increased in the presence of bile salts

11. Overview of Digestion of Dietary Lipids
Mouth CE
Stomach PL
Small
Intestine
TAG
Primary products of lipids digestion
2- monoacylglycerol
Free FA
Free cholesterol

12. Absorption of Lipids by Intestinal Mucosal Cells
In the jejunum, the primary products of lipids digestion (2- monoacylglycerol , Free FA & Free cholesterol ) together with bile salts form mixed micelles then absorbed at the brush border membrane
Mixed micelles are disc shaped clusters of amphipathic lipids that coalesce with their hydrophilic groups on the outside of the cluster & their hydrophobic groups on the inside
Short & medium chain length fatty acids
do not require mixed micelles for absorption
So, considered for dietary therapy for individuals
with malabsorption of other lipids.

13. Resynthesis of TAG, CE & PL inside intestinal cells
Long-chain fatty acids entering enterocytes are used to form TAG, PL & CE
Short & medium –chain fatty acids are not converted to their CoA derivative & are not re-esterified to 2-monoacylglycerol They are released directly into the portal circulation by serum albumin

14. Formation of Chylomicrons inside intestinal cells
Inside intestinal mucosal cells:
Newly synthesized triacylglycerol (TAG) & cholesterol esters (CE) are very hydrophobic & therefore are packaged as lipid droplets surrounded by a thin layer of phospholipids (PL), free cholesterol (C) & a protein molecule (apolipoprotein B-48 or apo B-48) forming the chylomicrons.
The outer layer (apo B-48) stabilizes the particle & prevents it from coalescing
Chylomicrons are released by exocytosis from villi of intestine into the lacteals to the thoracic duct of the lymphatic system to left subclavian vein to blood
Lacteals: are lymphatic vessels originating in villi of small intestine

15. Use of Dietary Lipids by the Tissues (Chylomicron Metabolism)
Type I
Hyperlipoproteinemia

16. Lipid Malabsorption
Lipid malabsorption result in increased lipids in the feces (steatorrhea) Steatorrhea can be caused by disturbances of: 1- Lipid digestion 2- Lipid absorption 3- Both
Liver causes:
Def. of bile acids production
Obstruction of CBD
Pancreatic causes:
as: cystic fibrosis
Intestinal causes
as: infection