digestion of dietary lipids digestion of dietary lipids

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Digestion of Dietary Lipids

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Page 1: Digestion of Dietary Lipids Digestion of Dietary Lipids

Digestion of Dietary Lipids

Page 2: Digestion of Dietary Lipids Digestion of Dietary Lipids

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

Page 3: Digestion of Dietary Lipids Digestion of Dietary Lipids

Adult ingestion of lipids per day is about 60-150 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 1- In mouth (limited) 2- In stomach 3- In small intestine : Emulsification of lipids (by bile acids & peristalsis) Degradation of lipids by pancreatic enzymes

Digestion of Dietary Lipids

Page 4: Digestion of Dietary Lipids Digestion of Dietary Lipids

Digestion of lipids In the Mouth & Stomach

Lingual lipase: secreted by glands at the back of the tongue.Gastric lipase: secreted by gastric mucosaBoth 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)

Page 5: Digestion of Dietary Lipids Digestion of Dietary Lipids

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 salts2- 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

Page 6: Digestion of Dietary Lipids Digestion of Dietary Lipids

• 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

Page 7: Digestion of Dietary Lipids Digestion of Dietary Lipids

Degradation of Dietary Lipids by Pancreatic Enzymes

The dietary lipids are enzymically degraded by pancreatic enzymes , whose secretion is

hormonally controlled

Page 8: Digestion of Dietary Lipids Digestion of Dietary Lipids

Triacylglycerol (TAG) Degradation

Pancreatic lipaseis 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 trypsinAnchors the lipase at lipid aqueous interface

Orlistat an antiobesity drug , inhibits gastric & pancreatic lipases causing decreased fat digestion & hence absorption resulting in weight loss

Page 9: Digestion of Dietary Lipids Digestion of Dietary Lipids

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

Phospholipid (PL) Degradation

Page 10: Digestion of Dietary Lipids Digestion of Dietary Lipids

Cholesteryl Ester (CE) Degradation

15-20% of dietary cholesterol is esterifiedCholesterol ester hydrolase (cholesterol esterase) activity is greatly increased in the presence of bile salts

Page 11: Digestion of Dietary Lipids Digestion of Dietary Lipids

Overview of Digestion of Dietary Lipids

CE

PL

TAG

Primary products of lipids digestion 2- monoacylglycerol Free FA Free cholesterol

Mouth

Stomach

Small Intestine

Page 12: Digestion of Dietary Lipids Digestion of Dietary Lipids

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 acidsdo not require mixed micelles for absorptionSo, considered for dietary therapy for individuals with malabsorption of other lipids.

Page 13: Digestion of Dietary Lipids Digestion of Dietary Lipids

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

Page 14: Digestion of Dietary Lipids Digestion of Dietary Lipids

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 bloodLacteals: are lymphatic vessels originating in villi of small intestine

Page 15: Digestion of Dietary Lipids Digestion of Dietary Lipids

Use of Dietary Lipids by the Tissues(Chylomicron Metabolism)

Use of Dietary Lipids by the Tissues(Chylomicron Metabolism)

Type IHyperlipoproteinemia

Page 16: Digestion of Dietary Lipids Digestion of Dietary Lipids

Lipid Malabsorption

Lipid malabsorption result in increased lipids in the feces (steatorrhea)Steatorrhea can be caused by disturbances of:1- Lipid digestion2- Lipid absorption3- Both

Pancreatic causes:as: cystic fibrosis

Intestinal causesas: infection

Obstruction of CBD

Liver causes:Def. of bile acids production