Lipids Flashcards
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
Endogenous pathway
- Most triglycerides packaged into VLDL are derived from diet and small fraction is made de novo in liver from dietary carbs
- IDL taken up by liver via Apo E and LDL receptor
- IDL triglycerides removed by hepatic triglyceride lipase on hepatic endothelial cells, thus making LDL
- LDL receptor abnormalities -> LDL elevation in blood -> hypercholesterolemia + premature artherosclerosis
Reverse cholesterol transport pathway
- HDL-mediated
- HDL maintains cholesterol equilibrium by removing excess cholesterol from cells
National cholesterol education program recommendation
Adults 20+ years have fasting lipoprotein profile performed once every 5 years (total chol, LDL-C, HDL-C, triglycerides)
Dyslipidemia in children 9-11 y/o
Abnormally low HDL-C or elevated non-HDL-C
Arteriosclerosis definition
Group of conditions that thickens arteries
Artherosclerosis definition
Specific type of arteriosclerosis
Arteriosclerosis
Cause?
General mechanism?
Diagnostic lab eval?
- Deposition of lipids, mainly esterified cholesterol causes heart disease/dyslipidemia
- Repeated cell injury -> plaques -> infiltration/cell proliferation to repair the site
- LDL central role in initiating/promoting plaque formation
- Key to do full lipid panel (total chol, HDL-C, LDL-C, and triglycerides)
Dyslipidemia two categories
- Hyperlipoproteinemia
- Hypolipoproteinemia
Hypercholesterolemia
- Strong correlation btwn hypercholesterolemia and heart disease mortality
- Familal hypercholesterolemia is genetically increased cholesterol levels
Hypertriglyceridemia
- 150-200 mg/dL = borderline high trig
- Influenced by insulin, glucagon, pituitary growth hormone, ACTH, thryotropin, epinephrine, and norepinephrine
- Treat through diet change, fish oil, and/or trig-lowering drugs
Combined hyperlipidemia
Elevated serum levels of total cholesterol and trig
Lp(a) elevation
- Elevated serum Lp(a) levels, esp in conjunction with LDL elevation
- Increased risk of CHD and CVD
Non-HDL cholesterol
Elevated levels associated with increased CVD risk even if LDL-C levels are normal
Triglyceride measurement
- Lipases cleave fatty acids and free glycerol to participate in one of many enzymatic sequences
- Second sequence: glycerol kinase and glycerophosphate oxidase coupled to same peroxidase color rxn
HDL methods
- HDL used to be chemically ppt to separate out
- Replaced with new class of direct/homogenous methods - automate quantification (can lack specificity for HDL in unusual specimens)
LDL methods + calculation
Calculate using Friedewald eqn
LDL-C = Total chol - HDL - (Trig/5)
