1. Lipid digestion and inter-organ transport Russian National Research Medical University Maxim A. Abakumov Moscow, 2014

2. Lipids Large group of organic compounds containing long hydrocarbon chains or rings Poorly sooluble in water Well soluble in organic solvents Usually large size molecules

3. Lipid functions Structural component of biological membranes Energy storage Hormones and vitamins Lipophilic bile acids important for lipid solubilization

4. Lipid classification Lipids Glycerides Fatty acids SaturatedUnsaturated Neutral glycerides Phospho glycerides Nonglyceride lipidsComplex lipids WaxesSphingolipidsSteroids Lipoproteins

5. Lipid classification Lipids Glycerides Fatty acids SaturatedUnsaturated Neutral glycerides Phospho glycerides Nonglyceride lipidsComplex lipids WaxesSphingolipidsSteroids Lipoproteins

6. Fatty acids Carboxylic acids with long (C 8 -C 20 ) hydrocarbon «tail» Saturated fatty acids contain only σ-bonds (single bonds) Unsaturated fatty acids contain also π-bonds (double bonds)

7. Fatty acids

8. Saturated fatty acids Have even number of carbon atoms Contain maximum hydrogen atoms Hydrocarbon chains (HC) are full length straight Have high melting point

9. Unsaturated fatty acids Have even number of carbon atoms Contain less hydrogen atoms then saturated FAs Each doble bond bent HC for 30° Have low melting point

10. Fatty acids

11. Trans- and cis-fatty acids Oleic acidElaidic acid Cis double bond Trans double bond

12. Fatty acids nomenclature

13. Fatty acids

14. Essential fatty acids

15. Lipid classification Lipids Glycerides Fatty acids SaturatedUnsaturated Neutral glycerides Phospho glycerides Nonglyceride lipidsComplex lipids WaxesSphingolipidsSteroids Lipoproteins

16. Triglycerides

17. Phospholipids X X Fatty acid chain GlycerolPhosphate

18. Lipid classification Lipids Glycerides Fatty acids SaturatedUnsaturated Neutral glycerides Phospho glycerides Nonglyceride lipidsComplex lipids WaxesSphingolipidsSteroids Lipoproteins

19. Sphingolipids Sphingosine RSphingolipid HCeramide PhosphocholineSphyngomyelin SugarGlycosphingolipid

20. Glycolipids

21. Fat digestion Most fat is presented as TGs Low water solubility Large size Low accebility for enzymes Bile acids create fat emulsion Size of fat drops decreases Surface increases Accebility for enzymes increases TGs are hydrolized Lipase Colipase Micells are formed Fatty acids are transported into cells

22. Fat digestion Most fat is presented as TGs Low water solubility Large size Low accebility for enzymes Bile acids create fat emulsion Size of fat drops decreases Surface increases Accebility for enzymes increases

23. Fat emulsification TGs are hydrophobic- solubilization is needed. Key players – bile acids Bile acids are cholesterol derivatives Synthesized in liver from AcCoA Amphiphilic molecules

24. Fat emulsification Nonpolar region Polar (charged) region Bile salt Emulsification Fat droplets coated with bile salts are suspended in water

25. Bile acids

26. Primary bile acids Synthesized in liver from cholesterol

27. Secondary bile acids Bacteria in gut

28. Conjugated bile salts Occurs in liver Both with primary and secondary bile acids Glycine or taurin are conjugated To carboxylic group on bile acid tale Glycine Taurine

29. Conjugated bile salts Glycoholic acid Tauroholic acid Cholic acid

30. Enterohepatic circulation of bile acids

31. Pancreatic lipase Hydrolyse TGs into 2 fatty acids and monoacylglyceride Extracellular enzyme Secreted by pancreas Esterase enzyme subclass

32. Fat digestion TGs are hydrolized Lipase Colipase Micells are formed Fatty acids are transported into cells

33. Pancreatic lipase Free fatty acids Pancreatic lipase hydrolase bonds between glycerol and fatty acids at positions 1 and 3 Position 1 Position 3

34. Colipase Small protein Cofactor for lipase Prevent lipase inactivation by bile salts Required for effecient lipase work in intestine Secreted as procolipase (inactive) Activated by trypsin

35. Colipase

36. Long chain TGs Long chain TGs (LCTG)– contain fatty acids with 14-22 carbon atoms Poor solubility in water Requires bile acids for digestion and transport Resinthesized in intestinal cells Combined with lipoproteins to form chylomicrons Transported in chylomicrons into lymphatic system Can be stored in adipose tissue prior to oxidation in liver

37. Long chain TGs

38. Medium chain TGs Medium chain TG (MCTG) – contain fatty acids with 8-10 carbon atoms Higher polarity, then LCTG Bile acids are not required for absorbtion Transported into blood in natural state Faster oxidized in liver Don’t go to adipose tissue

39. Medium chain TGs

40. Interorgan lipid transport Lipids are poorly soluble in water Special lipoprotein complexes are used for lipis solubilization Each lipoprotein complex transport lipids in one direction Main directions are 1) Intestine→Liver 2) Liver→Peripheral organs 3) Peripheral organs

41. Interorgan lipid transport Peripheral tissue Chylomicrons VLDL, LDL, IDLHDL

42. Lipoproteins in lipid transport

43. Lipoproteins

44. Lipoproteins in lipid transport

45. Chylomicrons Largest lipoprotein Contains largest amount of lipids Transport TGs from intestine to peripheral tissue Transport TGs and cholesterol to liver (remnant chilomicrons) Mostly dietary TGs Main proteins are: B-48, A, C, E Supresses cholesterol biosynthesysis

46. Chilomicrons

47. Very low density liporpotein VLDL Mostly contain endogenous TGs and cholesterol. Synthesized in liver Transport endogenous TGs from liver to peripheral tissue Main proteins are: B-100, C, E Same metabolism as chilomicrons except fact that VLDL are synthesized in liver

48. VLDL

49. Intermediate density lipoprotein IDL Contain both endogenous TGs and cholesterol esters (CE) Transport TGs and CE to peripheral tissue Synthesized from VLDL in blood stream by lipoprotein lipase (LPL) Main proteins are: B-100, E

50. Low density lipoprotein LDL Contain more CE then TG Transport CE from liver to peripheral tissue Synthesized from IDL (VLDL) in blood stream Main proteins are: B-100

51. IDL and LDL VLDL LPL Remnant VLDL (IDL) Liver internalization ApoB-100 (LDL-receptor) LPL HL LDL Liver internalization ApoB-100 (LDL-receptor) Peripheral tissue ApoB-100 (LDL-receptor) FA+cholesterol FA to peripheral tissue FA to peripheral tissue

52. Type Deficiency Lipid elevated in blood Lipoprotein elevated in blood Comments I Familial lipoprotein lipase(rare) apoC-II (rare) Triglyceride Chylomicro ns Red-orange eruptive xanthomas, Fatty liver Acute pancreatis Abdominal pain after fatty meal IIa Familial hypercholeste rolemia CholesterolLDL High risk of atherosclerosis and coronary artery disease Xanthomas of the Achilles tendon Xanthelasmas Corneal areus

53. High density lipoproteins HDL Contains largest amount of CE, less TG Transport cholesterol (CE) to liver from peripheral tissues Synthesized in liver and intestine as Apolipoprotein A1 Main protein are: A1

54. High density lipoproteins