lecture 24 - fat absorption & transport Flashcards
What are the 2 key molecules associated with fat metabolism?
triacylglycerol, cholesterol ester
What solubilises fat in the GI tract?
Bile salts
What are bile salts synthesised from, and where?
Cholesterol, in the liver
What hormone triggers the release of bile from the gall bladder?
CCK - cholecystokinin
What are the 2 purposes of micelle formation?
Bile salts aid in solubilising fats in an aqueous environment, Decrease size to increase surface area for digestion
What are the components of bile?
Water, bile acids, electrolytes, phospholipids, cholesterol, bile pigments
What are the 3 key hormones that regulate digestion?
Gastrin, Secretin, Cholecystokinin
What is the source of gastrin?
Stomach
What is the source of secretin?
Duodenum
What is the source of cholecystokinin?
duodenum
What is the major stimulus for the production of gastrin?
Protein containing food in the stomach
What is the major stimulus for the production of secretin?
HCl in duodenum - due to entry of acidic chyme
What is the major stimulus for the production of cholecystokinin?
Fats and amino acids in the duodenum
What is the action of gastrin?
Stimulates the secretion of gastric juices
What is the action of secretin?
Stimulates the secretion of alkaline bile (HCO3- and pancreatic fluids
What is the action of cholecystokinin?
Stimulates the release of pancreatic enzymes and bile from the gall bladder
How are triacylglycerols hydrolysed in micelles?
Pancreatic lipase and colipase enzyme system binds to the lipid/aqueous interface of the micelle and performs hydrolysis
What enzyme hydrolyses TAGs in micelle form in the small intestine?
Pancreatic lipase
On a chemical level, how does pancreatic lipase hydrolyse TAG, and what is the product?
Hydrolyse the bonds with fatty acids at positions 1 and 3 of the glycerol backbone, leaving 2-monoacylglycerol
What is the result of fat malabsorption in the GI tract?
Excess of fat and fat-soluble vitamins in the faeces
What is Xenical/Orlistat?
A potent inhibitor of pancreatic lipase that prevents TAG breakdown by forming a covalent bond with the lipase active site
What is the potent inhibitor of pancreatic lipase that prevents TAG breakdown?
Xenical/Orlistat
what is the function of lipoproteins?
Help to solubilise lipids for transport to tissues via the blood, and then provide a delivery system for lipid entry and exit of cells
What are the 5 key components of general lipoprotein structure?
Phospholipid capsule, unesterified cholesterol, esterified cholesterol, triglycerides, accessory proteins (apoproteins)
What are the 3 functions of apoproteins in lipoproteins?
Structure for assembly, ligands for cell surface receptors, act as enzyme cofactors
What apoprotein is used for structure in lipoprotein assembly?
apoB
What apoproteins are used as ligands for cell surface receptors?
apoE, apoB
What apoprotein is used as an enzyme cofactor?
apoCII (for lipoprotein lipase)
What apoprotein acts as a cofactor for lipoprotein lipase>
apoCII
What are the 4 main classes of lipoprotein?
Chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL)
What type of lipoprotein has the lowest density?
Chylomicrons
What type of lipoprotein has the highest proportion of protein?
High density lipoprotein (HDL)
What type of lipoprotein has the highest TAG proportion?
Chylomicron
What type of lipoprotein has the highest proportion of cholesterol?
low density lipoprotein (LDL)
What type of lipoprotein has the highest proportion of phospholipids?
High density lipoprotein (HDL)
How many lines should be seen on normal blood plasma gel electrophoresis, indicating the different types of lipoprotein present?
4
What are the 2 major lipid transport pathways?
Exogenous chylomicron pathway (dietary fat), endogenous VLDL/LDL pathway (endogenously synthesised fat)
Dietary fat is involved in which lipid transport pathway?
Exogenous chylomicron pathway
How are chylomicrons assembled?
TAGS and other lipids combine with apoB in the endoplasmic reticulum of intestinal epithelial cells to form chylomicrons
How do chylomicrons secreted from intestinal epithelial cells enter the blood stream?
Via the lymphatic system
Where is lipoprotein lipase found?
On the endothelial surface (inner surface) of capillaries
Where does lipoprotein lipase have the highest activity of TAG hydrolysis?
In heart, skeletal muscle and adipose tissue
What are the products of TAG hydrolysis by lipoprotein lipase?
fatty acids and 2-monoacylglycerol
What is the fucntion of hormone sensitive lipase?
Mobilises TAG stored in adipose tissue by hydrolysing TAG to glycerol and free fatty acids
What activates lipoprotein lipase?
apoCII (apoprotein)
If there are mutations to apoCII or lipoprotein lipase, what are the consequences?
Elevated levels of chylomicrons and plasma triacylglycerol
What is the disease caused by a defect to apoCII?
Familial apoCII deficiency
What is the disease caused by defects to apoE and LDL receptors?
Familial hypercholesterolaemia (FH)
What is the ‘bad’ cholesterol?
LDL
What is the ‘good’ cholesterol?
HDL
What is the affect of familial a hypercholesterolemia (FH) on blood cholesterol levels?
Increase 2 or 3 fold of LDL
What is the inheritance pattern of familial hypercholesterolemia (FH)?
Dominant - heterozygotes affected
What is familial hypercholesterolemia treated with?
Statins - which lower LDL and increase HDL
What are xanthomas?
Fatty growths under the skin
