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Lipid digestion and absorption for medical school

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Lipid digestion and absorption for medical school

  2. 2. V.S.RAVIKIRAN, MSc., Department of Biochemistry, ASRAM Medical college, Eluru-534005.AP, India. vsravikiran2013@gmail.com
  3. 3. 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
  4. 4. Challenges Lipids are not water soluble Triglycerides too large to be absorbed Digestive solution Triglycerides mix with bile and pancreatic secretions  Emulsification and digestion
  5. 5. 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
  6. 6. 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
  7. 7. 2. Digestion: Pancreatic juice: - Pancreatic lipase - Cholesterol estarase - Phospholipase A2 - Colipase Lipolytic enzymes colipase lipase TG particle
  8. 8. Hydrolysis of lipids  Triglycerides (TG) TG + H2O → Diglyceride + fatty acid (FA) Diglyceride + H2O → Monoglyceride (MG) + FA 2+ 2 H2O lipase O O O O R R O R O OH O OH R O R O O– + 2 H+
  9. 9. Cholesterol esters & phospholipids* (PL) ↓ esterase ↓ phospholipases FA + cholesterol (chol) FA + lyso PL In all cases, products are more polar than reactants O O O P O R O R OO OR – ** biliary & dietarybiliary & dietary
  10. 10. Physiologically important lipases Lipase Site of action Preferred substrate Product(s) Lingual / acid stable lipase Mouth , stomach TAGS with med chain FAS FFA+DAG Pancreatic lipase + co-lipase Small intestine TAGS with long chain FAS FFA+2MAG Intestinal lipase with bile acids Small intestine TAGS with med chain FAS 2FFA+glycerol Phospholipase A2 + 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
  11. 11. 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
  12. 12. Bile salts: synthesis, secretion  Synthesized in the liver. cholesterol Bile acid Bile acyl-CoA + amino acid ( glycine / taurine ) Bile salt
  13. 13. Biliary Lipid Secretion Sinusoidal Membrane BloodBlood HepatocyteHepatocyte Canalicular Membrane Bile SaltBile Salt ABCG5/G8 Cholesterol ABCB4 Phospholipid ABCB11 BileBile
  14. 14. Biliary Lipids Daily Secretion (g)Daily Secretion (g)Lipid ClassLipid Class Bile salts Phospholipids Cholesterol 24 11 2
  15. 15. Structure of Biliary and Intestinal Micelles Cholesterol BileBile SaltSalt PhospholipidPhospholipid
  16. 16. Biliary Lipid Transport DuodenumDuodenum JejunumJejunum IleumIleum ColonColon Biliary Transport and Storage Liver
  17. 17. Fat Digestion DuodenumDuodenum JejunumJejunum IleumIleum ColonColon Biliary Transport and Storage Liver
  18. 18. Fat Digestion I I I I II I II I II I II I Fatty Acids +Fatty Acids + LysophospholipidLysophospholipid PhospholipidsPhospholipids I I I TriglyceridesTriglycerides Fatty Acids +Fatty Acids + MonoglyceridesMonoglycerides I I II II I II I I I I I I I I I I I DietaryDietary Cholesterol esterCholesterol ester I I I II I FattyFatty acidsacids ++ cholestecholeste rolrol
  19. 19. Fat Absorption DuodenumDuodenum JejunumJejunum IleumIleum Biliary Transport and Storage ColonColon Liver
  20. 20. 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
  21. 21. Absorption: role of micelles Unstirred layer  200-500 μm 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
  22. 22. LymphLymph EnterocyteEnterocyte IntestinalIntestinal LumenLumen Cholesterol Absorption Cholesteryl Ester ACAT Cholesterol IITT NPC1L1 ABCG5/ G8
  23. 23. LymphLymph EnterocyteEnterocyte IntestinalIntestinal LumenLumen Triglyceride Absorption 2 Fatty Acid + Monoglyceride DGAT Triglyceride TTII
  24. 24. LymphLymph EnterocyteEnterocyte IntestinalIntestinal LumenLumen Phospholipid Absorption Phospholipid Fatty Acid + Lysophospholipid II
  25. 25. LymphLymph EnterocyteEnterocyte IntestinalIntestinal LumenLumen Chylomicron Formation With apoB48 Cholesteryl Ester Triglyceride Phospholipid
  26. 26. 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 cholesterolbile salts Sherwood, Fig.16-17
  27. 27. Formation and secretion of (A) chylomicron in intestinal and (B) VLDL in Hepatic cell.
  28. 28. 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 PL Lehninger et al., 3rd ed., Fig. 17-2
  29. 29. 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)  Chylomicron 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
  30. 30. Stomach gastric mobility Small intesti ne 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 +
  31. 31. triglycerides
  32. 32. 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
  33. 33. 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 Chyluria Chylothorax
  34. 34. 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.
  35. 35. 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 1818 4ATPs/TG EnterocyteEnterocyte oil drop TG