Metabolism - Lecture Twenty-Five Flashcards
Absorption and Transport of Fats includes the absorption of fats in the gastrointestinal tract, plasma lipoproteins and pathways of lipid transport and disorder of fat digestion and transport
Where do bile acids (bile salts) solubilise fat?
In the gastrointestinal tract
Synthesis of bile salts
Bile salts are synthesised from cholesterol in the liver and stored in the gall bladder as bile
Secretion of bile salts
The secretion of bile salts are in proportional to the amount of lipid and are secreted into the small intestine in response to cholecystokinin
Bile salts (in terms of detergents)
are powerful detergents with hydrophobic and hydrophilic surfaces
Bile salts (in terms of digestion)
form micelles with triacylglycerols to increase surface area for digestion
What does bile contain?
Water, bile acids, electrolytes, phospholipids, cholesterol and bile pigments
Increase in cholesterol
results in gall stones
Three examples given for regulation of digestion by polypeptide hormones
Gastrin, secretin and cholecystrokinin
Gastrin source
Stomach
Secretin source
Duodenum
Cholecystokinin source
Duodenum
Gastrin major stimulus for production
Protein-containing food in the stomach and also para-sympathetic nerves to stomach
Secretin major stimulus for production
HCl in duodenum
Cholecystokinin major stimulus for production
Fats and amino acids in the duodenum
Gastrin major actions
Stimulates secretion of gastric juices
Secretin major actions
Stimulates secretion of alkaline bile and pancreatic fluids
Cholecystokinin major actions
Stimulates release of pancreatic enzymes and stimulates release of bile from gallbladder
How are lipids emulsified?
By bile salts to form micelles (complex lips and protein structures)
What does the pancreatic lipase/co-lipase enzyme system bind to?
Lipid/aqueous interface of micelle and hydrolyses triacylglycerols
What do pancreatic lipase hydrolyse?
Fatty acids at positions 1 and 3 of glycerol backbone of triacylglycerol to form smaller micelles
What do small micelles contain?
Bile salts, free fatty acids, monoacylglycerol (and cholesterol)
Where a micelles absorbed?
Across the intestinal cell membrane
What does pancreatic lipase hydrolyses triacylglycerols into?
Free fatty acids and 2-monoacylglycerol
Fat malabsorption
leads to excess fat and fat soluble vitamins in faeces
How is fat malabsorption caused?
By conditions that interfere with bile or pancreatic lipase secretion, ie. pancreatitis, gall bladder or liver diseases
Example given of fat malabsorption
Orlistat
Orlistat
Makes a covalent linkage with a side chain near the co-lipase active site which forms a stable complex that blocks the active site of the lipase resulting in no hydrolysis of tracylglycerol and not available as free fatty acids
Lipoproteins
Help ‘solubilise’ lipids for transport in blood to tissues and provide a ‘delivery system’ for transporting lipids into and out of cells
Important functions of apoproteins
structural for assembly (apoB) and ligands for cell surface receptors (apoE and apoB) - enzyme cofactors (apoCII for lipoprotein lipase)
Four main lipoprotein classes
Chylomicrons, VLDL, LDL and HDL
Two major lipid transport pathways
Exogneous chylomicron pathway and endogenous VLDL/LDL pathway
Exogneous chylomicron pathway
Dietary fat
Endogenous VLDL/LDL pathway
Endogenously synthesised fat
Chylomicron assembly
Triacylglycerols and other lipids combine with apoB in the ER to form chylomicrons. Chylomicrons secreted from intestinal epithelial cells enter the bloodstream via the lymphatic system.
Chylomicrons
Can give plasma a ‘milky’ appearance after a fat-rich meal
Lipoprotein lipase enzyme location
Found on the endothelial surface
What does the lipoprotein lipase do?
Hydrolyses TAG in lipoproteins to glycerol and fatty acids highest activities in heart and skeletal muscle and adipose tissue
What is the lipoprotein lipase activated by?
ApoCll
Defects (by mutation) in either apoCII or lipoprotein lipase
Lead to elevated levels of chylomicrons and plasma triacylglycerol
Familial hypercholesterolmia (FH)
Common form of hyperlipidaemia which leads to premature atherosclerosis and is a dominant disorder
How is familial hypercholesterolmia caused?
By defect in LDL receptor gene (many different mutations)
LDL levels in familial hypercholesterolmia
2-3x higher than normal
How is familial hypercholesterolmia treated?
With ‘statins’ to lower LDL and increase HDL (‘good’ cholesterol)
Treatment for patients with high blood triglyceride levels?
Tricor (fenofibrate)
