Lipids
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Why are lipids important?
• Cell membrane constituents • Absorption of fat-soluble vitamins • Maintain membrane fluidity • Thermal insulator and cellular metabolic regulator • Hormone synthesis • Organ padding • Transporters
Lipids are mostly made from which source? Exceptions?
• Mostly made from carb sources • Except essential FAs must be eaten (found in plants)
How many esterified FAs does a triglyceride have?
3
Saturated fats
• NO bends in structure, pack tightly • Solid at RT • Animal sources • Neutral charge
Unsaturated fats
• Bends in structure, don’t pack tightly • Oil at RT • Plant sources • Neutral charge
Phospholipids
• Hydrophilic head group and hydrophobic tails • Amphipathic (hydrophilic/hydrophobic) • Synthesized in all organs, esp liver
Cholesterol
• Unsaturated steroid alcohol • Amphipathic • Animal sources • Plants - phytosterols • Synthesized in most tissues • Not readily catabolized • Small amt used for Vit D
Use of bile acid (cholic acid)?
Detergent to allow fat to be taken up and used
General lipoprotein structure + function
• Spherical • Size: 10 nm to more than 1 micron • Protein + lipids present • Function: Deliver fuel
Lipoproteins Apo A1 and Apo A2 are exclusively found where?
HDL
Lipoprotein Apo B 100 is exclusively found where?
LDL
Lipoprotein Apo B48 is exclusively found where?
Chylomicrons
Lipoprotein Apo(a) is exclusively found where?
Lipoprotein A
Function of apolipoproteins
Structural integrity and ligands
Chylomicrons Made when? Produced by? Function? How size affects plasma? Hydrophobic core composition?
• Made when we eat triglycerides • Produced by intestine • Functions to transport exogenous triglycerides (ones we eat) to the liver • Big so cause turbid/milky appearance of plasma, reflect lots of light • Hydrophobic core composition: 84% triglyceride + 7% cholesteryl esters
VLDL Produced by? Function? How size affects plasma? Hydrophobic core composition?
• Produced by liver • Functions to transport endogenous (hepatic-derived) triglycerides, mostly during fasting • Smaller than chylos, can cause some turbidity but not as buoyant so won’t float on top. Account for most turbidity during fasting hyperlipidemic plasma samples • Core comp: 65% triglycerides, 8% cholesteryl esters
LDL Produced by? Function? How size affects plasma? Hydrophobic core composition?
• Produced from lipolysis of VLDL in blood circulation • Function not given, but it gets uptaken by cells via LDL receptor and can cause foamy macrophages. LDL can build up on vessel wall and cause plaques. Macrophages come to clean them up • Super small so can go to extracellular space of vessel wall • More cholesteryl ester than triglyceride. Most cholesterol rich particle
HDL Produced by? Function? Hydrophobic core composition?
• Produced by liver and intestine • Functions to reverse cholesterol transport/remove LDL in arteries bc LDL irritates arteries • More cholesteryl ester than triglyceride
Lipoprotein (a) Similar to which particle? Elevate levels increase risk of? Used for what?
• LDL-like particles • Elevated levels increase risk of premature congenital heart disease (CHD) and stroke • Used to stratify risk in family history of CHD
Intermediate-Density Lipoproteins (ILDLs)
• Normally only transiently present between VLDL->LDL conversion • Elevated in rare inborn metabolic errors
Lipoprotein X
Abnormal lipoprotein found in patients with biliary cirrhosis or cholestasis
Name the 4 major pathways of lipoprotein metabolism
• Absorption • Exogenous • Endogenous • Reverse cholesterol pathway Pathways 1-3 transport lipids to peripheral cells. Pathway 4 tries to ta
Lipid absorption pathway during digestion
• Pancreatic lipase converts dietary lipids into more polar compounds with amphipathic properties by cleaving off fatty acids • Triglycerides -> mono/diglycerides • Cholesterol esters - free cholesterol • Phospholipids -> lysophospholipids
Exogenous pathway
• Chylomicrons initially go to lacteals (small intestine lymph vessels) and then to lymphatic ducts, eventually entering circ by thoracic duct • Apo C2 is a key protein in triglyceride metabolism, which is found on VLDL and critical to the activation of LPL • In liver, lysosomal enzymes break down fat and release free FAs, free cholesterol, and aa