B: Digestion and absorption of lipids

1. The majority of fats in the diet are triacylglycerols as well as phospholipids and cholesterols.
2. Fats = hydrophobic= emulsified to be digested.
   1. Fats droplets broken down into micelles = increase surface area.
      1. mechanical mixing and emulsifying action of bile salts
   2. Pancreatic lipase acts on droplets
      1. Chloesterol esters -> chloesterol and FA
      2. Triacylglycerol -> FA, diacylglycerols and monoaclyglycerols
      3. Phospholipids -> lysophospholipids and FA
   3. Lipase and gastric lipases important.
   4. Products of digestion, as well as fat soluble vitamins require BILE ACIDS for ABSORPTION.
      1. Excess bile salts recycled. Approx 5% in faeces.

1. Bile salts stick to fat droplets = emulsified. Lipases break down triglyceride emulsion droplets into FA and monoglycerides. These are then packaged into micelles absorped by microvilli of intestines. Inside, monoglyceride converted back to tryglyceride which aggregate to form chylomycrons. Chylomicrons move into lymph capillary, transporting them to the rest of the body.
   1. Chylomicrons in lymph fluid then drain to lymph nodes and join with larger lymph vessles.
   2. Arrows show lymph vessels draining small intestine packed with chylomicrons, giving vessel a milky appearance.
2. Blood plasma before meal = clear. After meal has cloudy appearance due to CMs scattering light.

   Annotations:

   • Plasma sample left over night, CMs form fatty band at top of liquid.

1. Mixed micelles absorbed into enterocyte. Monoglycerides and FA re-esterfiicated in SER to TAG. TAG is packed in the golgi into chylomicrons. Chylocmicrons exocytose into the draining lymph vessels. Only medium chain FAs and glycerol pass straight through enterocyte into capillary vessels. (Micelles large so longer process).

   Annotations:

   • Enterocyte - cell of intestinal lining. SER- smooth endoplasmic reticulum.  TAG- tryacylglycerol 
2. CM's transport lipids derived from diet (are exogenous)

Annotations:

• Lipoproteins are complexes of lipids, apolipoproteins and phospholipids. Apolipoproteins -  proteins that bind lipids together.

1. Lipids - insoluble. Transported in blood with proteins as LIPOPROTEIN PARTICLES.
2. Classes of lipoproteins - CM, VLDL,IDL,LDL,HDL (decreasing size/increasing density order)

   Annotations:

   • CM - chylomicrons VLDL- very low density lipoproteins IDL - intermediate density lipoprotiens   LDL- low density lipoproteins HDL - high density lipoproteins 
   1. Transport ENDOGENOUSLY synthesised triacylglycerols and chloesterol from liver to other tissues.
   2. Role/reason for transport of proteins.

      Annotations:

      • Structural, ligands for receptors, activators of enzymes, assoc. w/ lipoproteins so transported between.
   3. CMs rapidly cleared ---> HDLs present for much longer. CMs -> HDL decreasing triacyl glycerol and increasing protein and cholesterol. (CMs high in triacylglycerol, low in protein and cholesterol, hence are the largest but least dense.)

1. Pathway of delivery of exogenous fats (packaged asCMS) = SMALL INTESTINE --> LIVER --> PERIPHERAL TISSUES (smooth muscle, ovaries, testes etc)
   1. Small i. to liver = exogenous. Liver to tissue =endogenous.
   2. TG hydrolysis to deliver FAs to tissues, catalysed by lipoprotein lipase.

      Annotations:

      • TG = triglyceride
   3. CMs -> liver. VLDLs, IDLs and LDLs -> tissues (or return to liver to be reprocessed)

1. Dietary fat enters gut and is processed into NASCENT CMs. Proteins are added to nascent CMs as they mature. LPL reduces TAG content of mature CM as glycerol and FAs are proveided to muscle or adipose cells. CM remnants donate their proteins (to nascent CMs) and are transported to the liver for processing.

   Annotations:

   • NASCENT CMs- newly formed chylomicrons. Cll, E proteins added to nascent CMs LPL- lipoprotein lipase, present on lumen of BV epithelial cells.
2. LPL - on surface of capillaries, is activated by apoCll. Hydrolyse TAG to glycerol and FAs which enter cells for oxidation or storage.

1. Nascent VLDLs mature by addition of Cll and E proteins. VLDLs are converted for storage by LPL (activated by Cll) as ADIPOSE tissue. VLDL remnant donates Cll to nascent VLDLs and itself becomes an IDL. IDL is then directly recylced in the liver, or donates E protein to become LDL and then is recycled by liver. Liver recycles these into VLDLs again.

   Annotations:

   • LDL can also bind its B100 receptor as an effective way of delivering cholesterol to other peripheral tissues.

1. Functions of HDL
   1. Removes chol. from peripheral tissues. Transferred as VLDL, IDL or LDL for recirculation or directly carried back to liver for degredation or secretion.
   2. Provides apoproteins for other lipoproteins

      Annotations:

      • APOPROTEIN - the protein portion of a molecule or complex. Joins to a nonprotein protein molecule(s), such as a lipoprotein.
2. Liver makes and exports discoidal, nascent HDL particles.
3. Cholesterol is transferred from peripheral tissues to NASCENT HDL. Synthesis of cholesterol ester, CE, by lecithin acyltransferase, LCAT.

   Annotations:

   • LCAT is found within HDL.
   1. Spherical, mature HDL is formed.
4. Direct transfer of HDL cholesterol to liver, or via VLDL, IDL and LDL (through the action of cholesterol ester transfer protein, CETP).

1. Mammals cannot incorporate double bonds beyond carbon 9, need omega 3 and omega 6 fats for the synthesis of a wide range of improtant lipid molecules, eg thromboxanes, prostaglandins, leukatrienes...

   Annotations:

   • w = omega symbol omega is the methyl carbon at the end.
2. Linoleic acid, 9,12-octadecanoic acid, 18:2 w-6,9