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The Small Intestine: Absorption 2 Lecture 5

The Small Intestine: Absorption 2 Lecture 5. Professor John Peters. Lipid A bsorption (1). Free Fatty acids and monoglycerides. Transfer between mixed micelles and the apical membrane of enterocytes entering by the cell by passive diffusion. Fatty acids Monoglycerides.

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The Small Intestine: Absorption 2 Lecture 5

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  1. The Small Intestine: Absorption 2Lecture 5 Professor John Peters

  2. Lipid Absorption (1) Free Fatty acids and monoglycerides • Transfer between mixed micelles and the apical membrane of enterocytes entering by the cell by passive diffusion Fatty acids Monoglycerides • Short chain (i.e. 6 carbon) and medium (i.e. 8-12 carbon ) fatty acids diffuse through the enterocyte, exit through the basolateral membrane and enter the villus capillaries • Long chain fatty (i.e.  12 carbon) fatty acids and monoglycerides are resynthesized to triglycerides in the endoplasmic reticulum and are subsequently incorporated into chylomicrons

  3. Lipid Absorption (2) – Chylomicron Formation Carried in lymph vessels to systemic circulation (subclavian vein) via the thoracic duct Monoglyceride Triglyceride synthesis Cholesterol esters Free fatty acid Nascent chylomicron Chylomicron Endoplasmic reticulum Phospholipid synthesis Apolipoprotein (ApoB-48) Exocytosis Central lacteal

  4. Lipid Absorption (3) – Chylomicron Processing • Chylomicron enters systemic circulation into the subclavian vein via the thoracic duct and distributed to tissues • Chylomicron triglyceride metabolised in capillaries (particularly muscle and adipose tissue) by lipoprotein lipase present on endothelial cells • Free fatty acids and glycerol released initially bind to albumen and are subsequently taken up by tissues • Remainder of chylomicron is a chylomicron remnant, enriched in phospholipids and cholesterol • Chylomicron remnant undergoes endocytosis by hepatocytes – cholesterol released to: • be stored • secreted unaltered in bile • oxidised to bile salts

  5. Lipid Absorption (4) – Cholesterol Absorption • Once thought to be passive (similar to free fatty acids and monoglycerides) • Now appreciated to be mainly due to transport by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 (NPC1L1) protein • Ezetimibe binds to NPC1L1, prevents internalization, and thus cholesterol absorption. Used in conjunction with statins in hypercholesterolaemia

  6. Absorption of Ca2+ • Occurs by passive (i.e. paracellular; whole length of small intestine) and active (i.e. transcellular; mainly duodenum and upper jejunum) transport mechanisms Ca2+ (high lumenal Ca2+) Ca2+ Ca2+-calbindin-D Ca2+ (low lumenal Ca2+) • With [Ca2+] in chyme  5 mM absorption is mainly active 3Na+ Ca2+ • Active Ca2+ absorption is regulated by 1,25-dihydroxyvitamin D3 (calcitriol) and parathyroid hormone (increases 1,25-dihydroxyvitamin D3 synthesis) Ca2+ (high lumenal Ca2+) Ca2+ channel (TRPV6) – expression increased by 1,25- dihydroxyvitamin D3 Ca2+-ATPase (PMCA1) – expression increased by 1,25-dihydroxyvitamin D3 Sodium/calcium exchanger (NXC1)

  7. Absorption of Iron • Iron – important constituent of haemoglobin, myoglobin, many enzymes Ferratin (storage form of iron) • 12-15 mg ingested daily – only 3-10 % absorbed (female more than male) Fe3+Fe2+ Apoferratin + Fe2+  Fe3+ (Vit C) Fe2+ Fe2+ + Transferrin e.g. haemoglobin synthesis Haem oxidase Transferrin-Fe2+ Haem Divalent metal transporter 1 (DMT1) Haem carrier protein 1 Ferroportin (negatively regulated by the hormone hepcidin released from liver when body iron levels are high) – major control on iron absorption

  8. Absorption of Vitamins Fat soluble vitamins (i.e. A, D, E and K) • Incorporated into mixed micelles • Usually passively transported into enterocytes • Incorporated into chylomicrons, or VLDLs • Distributed by intestinal lymphatics Water soluble vitamins (i.e. B vitamins (but not B12), C, H • Transport processes in the apical membrane are similar to those described for monosaccharides, amino acids and di- and tri-peptides For example: • Vitamin B9 – the Na+-independent proton-coupled folate transporter 1; FOLT) • Vitamin C – the Na+-dependent vitamin C transporters (SVCT1 and 2) • Vitamin H – the Na+-dependent multivitamin transporter (SMVT)

  9. Absorption of Vitamin B12 (cobalamin) • Present in minute amounts in the diet (5-15 g day – daily requirement approximately 6 g per day, hence efficient and selective absorption required Vitamin B12 ingested in food Salivary glands secrete haptocorin Stomach acid releases vitamin B12 from food Haptocorin binds vitamin B12 released in stomach Stomach parietal cells release intrinsic factor Pancreatic proteases digest haptocorin in small intestine, vitamin B12 released Vitamin B12 binds to intrinsic factor in small intestine Vitamin B12-intrinsic factor complex absorbed in terminal ileum by endocytosis

  10. Summary • After this lecture and personal study, you should be able to • Describe how free fatty acids and monoglycerides are absorbed in the small intestine • Indicate how the absorption of free fatty acids and monoglycerides differs from that of cholesterol • Explain how chylomicrons are formed, transported and processed • Explain how the absorption of Ca2+ and iron are regulated processes • Outline the mechanisms that underlie the absorption of water- and fat- soluble vitamins • Explain why the absorption of vitamin B12 is a special case that requires a complex series of events

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