Lipid Metabolism

Fatty acids have four major physiologic roles in the cell:
• Building blocks of phospholipids and glycolipids
• Added onto proteins to create lipoproteins, which targets them to membrane locations
• Fuel molecules - source of ATP
• Fatty acid derivatives serve as hormones and intracellular messengers


Absorption and Mobilization of Fatty Acids
• Most lipids are triacylglycerols, some are phospholipids and cholesterol.
• Digestion occurs primarily in the small intestine.
• Fat particles are coated with bile salts (amphipathic) from gall bladder.
• Degraded by pancreatic lipase (hydrolyzes C-1 and C-3 ---> 2 fatty acids and 2-monoacylglycerol).
• Can then be absorbed by intestinal epithelial cells; bile salts are recirculated after being absorbed by the intestinal epithelial cells.
• In the cells, fatty acids are converted by fatty acyl CoA molecules.
• Phospholipids are hydrolyzed by pancreatic phospholipases, primarily phospholipase A2.
• Cholesterol esters are hydrolyzed by esterases to form free cholesterol, which is solubilized by bile salts and absorbed by the cells.
• Lipids are transported throughout the body as lipoproteins.
•Lipoproteins consist of a lipid (tryacylglycerol, cholesterol, cholesterol ester) core with amphipathic molecules forming layer on outside.

Lipoproteins

•Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids and contain cell-targeting signals.
•Lipoproteins classified according to their densities:
ochylomicrons - contain dietary triacylglycerols
ochylomicron remnants - contain dietary cholesterol esters
overy low density lipoproteins (VLDLs) - transport endogenous triacylglycerols, which are hydrolyzed by lipoprotein lipase at capillary surface
ointermediate-density lipoproteins (IDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis and converted to LDLs
olow-density lipoproteins (LDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis; major carrier of cholesterol in blood; regulates de novo cholesterol synthesis at level of target cell
ohigh-density lipoproteins(HDL) - contain endogenous cholesterol esters released from d