Download Biochemistry Ch 32 585-596 [4-20

Biochemistry Ch 32 585-596
Digestion and Transport of Dietary Lipids
Digestion of Triacylglycerols – triacylglycerols are the major fat in human diet; they contain a
glycerol backbone + 3 fatty acids
-digestion involves hydrolysis to fatty acids and 2-monoacylglycerol in the intestine
-depends on the length of fatty acid chains
-lingual/gastric lipases hydrolyze short + medium chain fatty acids (<12C)
-mammary gland produces milk, which contains long-chain fatty acids
Action of Bile Salts – fat enters small intestine and is emulsified by bile salts, which are
amphipathic compounds synthesized by liver and secreted by gallbladder
-CCK stimulates contraction of gallbladder and bile salt secretion
-bile salts bind globules of fat as they are broken up by peristalsis in intestine
-emulsified fat is attached by digestive enzymes from pancreas
Action of Pancreatic Lipase – secreted along with another protein, colipase in response to CCK
-secretin is released by intestine in response to acidic materials
-secretin signals liver, pancreas, and intestinal cells to secrete HCO3 to raise pH of intestine for
action of intestinal digestive enzymes
-Bile salts INHIBIT pancreatic lipase by coating substrate and not allowing access to enzyme
-Colipase binds dietary fat and to lipase to relieve inhibition and enhances lipase activity
-Pancreatic lipase then hydrolyzes fatty acids of ALL chain lengths from positions 1 and 3 of
glycerol to produce free fatty acids and 2-monoacylglycerol w/ fatty acid at position 2
-pancreas also produces esterases that remove fatty acids from compounds and PLA2 that
digests phospholipids to a free fatty acid and lysophospholipid
Absorption of Dietary Lipids – fatty acids and 2-monoacylglycerols, also cholesterol, vitamins,
etc. are packaged into micelles and emulsified by bile salts (concentration needs to be 5-15mM)
-micelles travel through layer of water to microvilli on surface of intestinal cells, where the fatty
acids, 2-monoacylglycerol, and other lipids are absorbed, but bile salts are NOT ABSORBED
-Bile salts are reabsorbed in the ILEUM and travel back to liver, which secretes them again
-short/medium chain fatty acids (C4-12) do NOT NEED bile salts for absorption
-transported to liver bound to serum albumin
Synthesis of Chylomicrons – inside intestinal epithelium, fatty acids and 2-monoacylglycerols
are converted back to triacylglycerols in sER enzymatic reactions
-fatty acids are activated to fatty acyl-CoA and reacts with 2-monoacylglycerol  diacylglycerol,
which reacts with another fatty acyl-CoA to form a triacylglycerol
-triacylglycerols are transported in lipoproteins because they are insoluble in H2O, and so
intestine cells package triacylglycerols with proteins and phospholipids into chylomicrons which
contains cholesterol and fat-soluble vitamins, but MAJOR COMPONENT is triglyceride
-protein component of lipoproteins are known as apoproteins
-Major apoprotein in chylomicrons is apoB-48, which is related to B-100 which is synthesized in
liver and is found in VLDLs; both encoded by same gene, apoB-48 undergoes RNA editing to 48%
of the size of B-100
-protein component of lipoproteins synthesized in rER, and lipids in sER
-Olestra is fat substitute without calories from fat (sucrose with fats), and cannot be digested
Transport of Dietary Lipids in Blood – chylomicrons secreted by intestinal epithelial cells into
chyle of lymphatic system enter blood through thoracic duct
-chylomicrons enter blood 1-2 hours after start of a meal
-they are called nascent chylomicrons until receiving proteins from HDL, becoming “mature”
-HDLs transfer proteins such as apoE and apoCII
-apoE is recognized by membrane receptors on liver cells for endocytosis/degradation
-apoCII activates lipoprotein lipase (LPL), an enzyme on capillary endothelial cells within
muscle and adipose to digest triacylglycerols on chylomicrons and VLDL in blood
-chylomicrons are the least dense of all of the lipoproteins
Fate of Chylomicrons – triacylglycerols on chylomicrons are digested by LPL attached to
proteoglycans in basement membranes of endothelial cells that line capillary walls
-LPL is produced by adipose cells, muscle, and lactating mammary gland
-adipose LPL has higher Km than muscle, therefore adipose LPL is more active after a meal,
when chylomicron levels are elevated in the blood
-INSULIN increases levels of LPL synthesis from adipose after a meal to facilitate digestion
-fatty acids released from triacylglycerols by LPL are not soluble, but become attached to
albumin
-major fate of fatty acids is storage as triacylglycerol in adipose tissue, but can also be oxidized
for energy in muscle and other tissues
-since muscle LPL has lower Km, muscle obtains fatty acids from blood whenever they
are needed for energy, even if concentration of lipoproteins is low
-glycerol released from chylomicron triacylglycerols by LPL used for liver triacylglycerol synthesis
-portion of chylomicron that remains in blood after LPL action is known as a chylomicron
remnant, which has LOST apoC molecules, which exposes apoE and binds to liver for
degradation by lysosomes
-People can lose weight by inhibiting pancreatic lipase which results in fat digestion and
absorption
-orlistat is a drug that is derivative of lipstatin, a lipase inhibitor in bacteria
-Heparin is polysaccharide component of proteoglycans used as an anticoagulant by binding to
antithrombin III and activating to inhibit clotting factors
-heparin binds LPL on capillaries to dislodge it, and loss of activity increases blood lipids
Microsomal Triglyceride Transfer Protein – required for assembly of chylomicrons within ER of
enterocyte
-a subunit called Protein Disulfide Isomerase (PDI) has a role that is not known
-bigger subunit contains triglyceride transfer activity, and MTP accelerates transport of
triglycerides, cholesterol esters, and phospholipids across membranes of subcellular organelles
-lack of this enzyme leads to abetalipoproteinemia – affects chylomicron assembly in
the intestine and VLDL assembly in the liver
-both particles require B apoprotein for assembly (B-48 and B-100), since MTP binds B
apoproteins
-MTP activity is necessary to transfer triacylglycerol formed within ER to apoB protein
-symptoms of abetalipoproteinemia include lipid malabsorption, caloric deficiencies, etc..
-MTP inhibitors have been investigated for their role on circulating lipid and cholesterol levels