Digestion and absorption of lipid ط Digestion of lipid, Lingual and gastric lipase ط Pancreatic lipase and formation of micelle ط Role of bile salts and bile acids, emulsification of fat ط Absorption of lipid from intestinal cells and release as Chylomicron into lymphatic system D

Introduction · Source of lipids: diet (plant & animals) and biosynth (excess carbohydrates, prt & other FAs) · Dietary fat consist of 90% TG and 10% PL, C, CE, FA · Lipids are soluble in organic solvents, but not in aqueous solutions (hydrophobic) => no Enz acess · If lipids are hydrolyzed => aggregates (poor absorption) · Five phases for dietary lipids digestion and absorption:

Dietary Lipids Digestion 1. fig26.28, Hydrolysis: Oil Phase  Lingual / Gastric Lipase (stomach- slow)  Emulsion Droplets (TG / DG / MG / FAs) 2. Solubilisation: a) Emulsion Droplets (Intestine)  · Pancreatic Lipase (activated by colipase) & BS / BA (duodenum) for TG / DG => MG · Pancreatic Esterase for CE => C · Pancreatic Phospholipase (activated by trypsin) & BS / BA for PL  Mixed Micelles (MG / FAs / C / PL) b) Micelles (intestinal lumen)  BS / BA  Micelles (cell surface) …

Dietary Lipids Absorption 3. fig26.27, Epithelial cell (enterocytes) uptake: a) Medium-chain FAs (6-12C) => pass through cell => capillaries (bld) => bind to Albumin => Liver b) Long-chain FAs (>12C) / MG => diffuse through membrane (gradient) => cytosol => bind to I-FABP => transport to End Retic … Unabsorbed lipids reach lower small intestine / colon and metab by bact. or excreted (Steatorrhea) 4. Packaging: End Retic (LC-FAs + MG) => re-synth TG => form a globule (TG) => absorbed by Apo LP & PL (Chylomicron: TG >85%) => through Golgi => reach plasma membrane … 5. Exocytosis: Plasma membrane (Chylom) => release into intracellular space => fusion into intestinal lymph nodes … Through Lymph vessels, Chylom drain into veins via thoracic duct and reach lung through capillaries then transport to peripheral tissues (AT, muscle) for FA storage as TG or to liver for metab.

BA Solubilisation 1. fig26.33, BAs solubilise fat in micelles (small lipid aggregates) that is smaller than emulsion droplets 2. fig26.34, BAs are arranged in micelles where they occupy the edge: · so that its hydrophilic groups are exposed to water soluble enzyme (lipases) · this cause constrains of a polar hydrophobic group of lipids (PL, FAs, C) 3. BAs provide major vehicle for lipids and lipid soluble vitamins (A, D, E, K) 4. fig26.35, Types of BAs and BS: Main primary BAs: Cholic / Chenodeoxycholic Secondary BAs: Deoxycholic / Lithocholic 5. BSs are conjugates of BAs (to glycine or taurine): Glycocholic or Cholyglycine 6. fig26.36, Released BA to intestine are reabsorbed back to liver via enterohepatic circulation

: Storage and mobilization of fatStorage and mobilization of fat ط Sites and synthesis of TAG : Liver and adipose tissues ط Steps and regulation of storage of fat ط Lipolysis : Steps and key enzyme ط Hormone sensitive lipase, regulation of lipolysis D

Storage of TG 1. fig9.14, Biosynthesis: most tissues can synth TG from DHAP through excess protein & carbohydrates Glc ==> GAP + DHAP a) DHAP  Reductase (–NADH)  G3P  Acyl transferase (–FACoA)  LPA b) LPA  Acyl transferase (–FACoA)  PA i. ==> other complexed lipids (phospholipids) ii.  Phosphotidate Phosphatase (+Pi)  DG c) DG i. Other complexed lipids (phospholipids) ii.  Acyl transferase (–FACoA)  TG * GAP ==> Pyr * DHAP  Acyl transferase (–FACoA)  ADHAP => i. ==> Ether lipids ii.  Reductase (–NADPH)  LPA * Glycerol  Glycerol Kinase (phosphorylation)  G3P (w.AT has no enzyme)

* fig, FA  Acyl CoA Synthatase (–CoA/ATP/+H2O)  FACoAfig

2. Liver & w.AT synth, store & hydrolyze TG 3. Skeletal & cardiac muscle store TG for local consumption 4. TG is stored in the cytoplasm as liquid droplets (½ life few days) 5. Intestinal mucosa does not require PA to synth TG: MG  DG

Mobilization of TG Hydrolysis sequence (1st step) of stored TG depends on HSL. This balance control is to avoid obesity. TG  HSL  FA + DG figfig, HSL “inactive”  Kinase (–INS/+Glg)  HSL-P “active” HSL-P  P-tase  HSL DG  Lipase  FA + MG MG  Lipase  FA + Glycerol FA binds to albumin (transporter) in capillaries Glycerol => DHAP => glycolysis / gluconeogenesis

figfig, HSL “inactive”  Kinase (–INS/+Glg)  HSL-P “active” HSL-P  P-tase  HSL