lipids- digestion & absorption

LIPIDS : DIGESTION AND ABSORPTION: 

LIPIDS : DIGESTION AND ABSORPTION

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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

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

IN STOMACH: 

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

IN SMALL INTESTINE: 

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

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

Hydrolysis of lipids: 

Hydrolysis of lipids Triglycerides (TG ) TG + H2O → Diglyceride + fatty acid (FA ) Diglyceride + H2O → Monoglyceride (MG ) + FA + 2 H +

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Cholesterol esters & phospholipids* (PL) ↓ esterase ↓ phospholipases FA + cholesterol ( chol ) FA + lyso PL In all cases, products are more polar than reactants * biliary & dietary

Physiologically important lipases: 

Physiologically important lipases Lipase Site of action Preferred substrate Product(s) Lingual / acid stable lipase Mouth , stomach TAG S with med chain FA S FFA+DAG Pancreatic lipase + co-lipase Small intestine TAG S with long chain FA S FFA+2MAG Intestinal lipase with bile acids Small intestine TAG S with med chain FA S 2FFA+glycerol Phospholipase A 2 + 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

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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

Bile salts: synthesis, secretion: 

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

Biliary Lipid Secretion: 

Biliary Lipid Secretion Sinusoidal Membrane Blood Hepatocyte Canalicular Membrane Bile Salt ABCG5/G8 Cholesterol ABCB4 Phospholipid ABCB11 Bile

Biliary Lipids: 

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

Structure of Biliary and Intestinal Micelles: 

Structure of Biliary and Intestinal Micelles Cholesterol Bile Salt Phospholipid

Biliary Lipid Transport: 

Biliary Lipid Transport Duodenum Jejunum Ileum Colon Biliary Transport and Storage Liver

Fat Digestion: 

Fat Digestion Duodenum Jejunum Ileum Colon Biliary Transport and Storage Liver

Fat Digestion: 

Fat Digestion I I I I I I I I I I I I I I I I Fatty Acids + Lysophospholipid Phospholipids I I I Triglycerides Fatty Acids + Monoglycerides I I I I I I I I I I I I I I I I I I I I Dietary Cholesterol ester I I I I I I Fatty acids + cholesterol

Fat Absorption: 

Fat Absorption Duodenum Jejunum Ileum Biliary Transport and Storage Colon Liver

Absorption from lumen : 

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

Absorption: role of micelles: 

Absorption: role of micelles Unstirred layer 200-500 μ m 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

Cholesterol Absorption: 

Lymph Enterocyte Intestinal Lumen Cholesterol Absorption Cholesteryl Ester ACAT Cholesterol I T NPC1L1 ABCG5/G8

Triglyceride Absorption: 

Lymph Enterocyte Intestinal Lumen Triglyceride Absorption 2 Fatty Acid + Monoglyceride DGAT Triglyceride T I

Phospholipid Absorption: 

Lymph Enterocyte Intestinal Lumen Phospholipid Absorption Phospholipid Fatty Acid + Lysophospholipid I

Chylomicron Formation: 

Lymph Enterocyte Intestinal Lumen Chylomicron Formation With apoB48 Cholesteryl Ester Triglyceride Phospholipid

Enterohepatic circulation (bile salt recycling): 

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 cholesterol bile salts Sherwood, Fig.16-17

Formation and secretion of (A) chylomicron in intestinal and (B) VLDL in Hepatic cell.: 

Formation and secretion of (A) chylomicron in intestinal and (B) VLDL in Hepatic cell.

Packaging for transport: 

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 Lehninger et al., 2nd ed., Fig. 16-2 PL Lehninger et al., 3rd ed., Fig. 17-2

Fate of dietary lipids:: 

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 ) C hylomicron 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

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Stomach gastric mobility Small intestine Dietary lipids Degradation of dietary lipids cholecytokinin - Gut Endocrine cells (enlarged) + Secretin (in blood) pancreas + bicarbonate secretes Pancreatic lipase secretes bile Gall bladder secretes + Hormonal control +

Abnormalities of maldigestion/malabsorption: 

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

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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

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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 .

Summary of lipid digestion & absorption: 

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 18 4ATPs/TG Enterocyte oil drop TG