Lecture 24: ABSORPTION AND TRANSPORTATION OF FATS Flashcards
What do bile acids do?
Solubilize fats in the gastrointestinal tract by intercalating non-covalently
How are bile acids synthesised?
From cholesterol in the liver and stored in the gall bladder as bile
Where are bile acids secreted?
Into the small intestine in response to cholecystokinin
What are bile salts described as?
Powerful detergents with hydrophobic and hydrophilic surfaces
What do bile salts form?
Micelles with triacylglycerols to increase surface area for digestion
What does bile contain?
Water, bile acids, electrolytes, phospholipids, cholesterol and bile pigment (bilirubin)
What are examples of bile acids?
Glycocholic acid and taurocholic acid
What is the result of increased cholesterol?
Gall stones
What are hormones involved in regulation of digestion?
Cholecystokinin, gastrin and secretin
What is the source of cholecystokinin?
Duodenum
What is the major stimulus for production for cholecystokinin?
Fats and amino acids in the duodenum
What are the major actions of cholecystokinin?
Stimulates release of pancreatic enzymes and release of bile from the gall bladder
What is the source of gastrin?
Stomach
What is the major stimulus for production of gastrin?
Protein-containing food in the stomach, also parasympathetic nerves to the stomach
What are the major actions of gastrin?
Stimulates secretion of gastric juices
What is the source of secretin?
Duodenum
What is the major stimulus for production of secretin?
HCl in the duodenum
What are the major actions of secretin?
Stimulates secretion of alkaline bile and pancreatic juices
What happens with lipids?
They are emulsified by bile salts to form micelles
What does the pancreatic lipase/colipase enzyme system do?
Bonds to lipid/aqueous interface of micelles and hydrolyses triacylglycerols
What does pancreatic lipase do?
Hydrolyses fatty acids at position 1 and 3 of backbone of triacylglycerol to give free fatty acids and 2-monoacylglycerol
What is the result of pancreatic lipase hydrolysing fatty acids?
Smaller micelles form containing bile salts, free fatty acids, monoacylglycerol (and glycerol)
What happens with micelles?
They are absorbed across the intestinal cell membrane
What does the small intestine have?
Specialised structures that create a vast surface area for absorption
What are the specialised structures of the small intestine?
Villi and microvilli
What does fat malabsorption lead to?
An excess of fat and fat soluble vitamins in the faeces
What is fat malabsorption caused by?
Conditions that interfere with bile or pancreatic lipase secretion - pancreatitis, gall bladder or liver diseases
What is a potent inhibitor of the pancreatic lipase active site?
Xenical (orlistat)
How does xenical inhibit pancreatic lipase?
By forming a covalent bond
What do lipoproteins help?
Solubilise lipids for transport in blood to tissues
What do lipoproteins provide?
A delivery system for transporting lipids into and out of cells
What are the important functions of apoproteins?
Structural for assembly (apoB), ligands for cell surface receptors (apoE and apoB) and enzyme cofactors (appCII for lipoprotein lipase)
What is the general lipoprotein structure?
Phospholipids, unesterified cholesterol, esterfied cholesterol and apoproteins with hydrophobic interior and hydrophilic exterior. Triacylglycerides found inside
What are the four main lipoprotein classes (from high lipid content to low)?
Chylomicrons, very low density (VLDL), low density (LDL), high density (HDL)
What is the process of TAG synthesis?
2-monoacylglycerol + free fatty acids in activated coenzyme form»_space;> diacylglycerol + free fatty acids in activated coenzyme form»_space;> triacylglycerol + apoproteins + other lipids»_space;> chylomicrons
What are the lipid transport pathways?
Exogenous chylomicron pathway (uptake of dietary fat) and endogenous VLDL/LDL pathway (endogenously synthesised fat)
What do triacylglycerols and other lipids combine with?
apoB int he ER to form chylomicrons
Where are chylomicrons secreted?
From intestinal epithelial cells and enter the bloodstream via the lymphatic system
What appearance do chylomicrons give plasma?
A milky appearance after a fat-rich meal
What is lipoprotein lipase?
An enzyme found on endothelial surfaces
What does lipoprotein lipase do?
Hydrolyses TAG in lipoproteins to glycerol and fatty acids
Where is lipoprotein lipase the most active?
In the heart, skeletal muscle and adipose tissue
What is lipoprotein lipase activated by?
apoCII
What do defects (by mutation) in either apoCII or lipoprotein lipase lead to?
Elevated levels of chylomicrons and plasma triacylglycerol
How is LDL determined?
total cholesterol - triaclyglyceride/5 - HDL
How is VLDL determined?
triacylglyceride/5
What are some inherited lipid disorders?
Familial ApoCII deficiency and familial hypercholesterolaemia
What is familial hypercholesterolaemia?
A common form of hyperlipidaemia which leads to premature atherosclerosis
What is familial hypercholesterolaemia cause by?
Defect in LDL receptor gene (many different mutations)
What type of disorder is familial hypercholesterolaemia?
Dominant
What do LDL (‘bad’ cholesterol) levels in familial hypercholesterolaemia do?
Are 2-3x higher than normal
What is familial hypercholesterolaemia treated with?
Statins to lower LDL and increase HDL (‘good’ cholesterol)
What is a symptom of familial hypercholesterolaemia?
Xanthomas - fatty growths under the skin
What can patients with high blood triglyceride levels be treated with?
Tricor (fenofibrate)
What are high blood triglyceride levels indicated by?
Milky plasma in centrifuged blood
