Lipids and Atherosclerosis Flashcards
1
Q
Fatty Acid Synthesis
A
- FAs are synthesized in various tissues through a lipogenic pathway
- Tissues: liver, intestine, & adipose cells from glucose
- Pathway: regulated by the hormones insulin, glucagon, & somatostatin
- Availability of initial substrates & products of this pathway influence lipogenesis
2
Q
Lipid Metabolism
- Lipids
- Most important simple lipids
- Most important complex lipids
A
- Lipids
- Structural & bioregulatory components o fhuman cells & plasma lipoproteins
- Simple or complex
- Complex: derived from simple by covalent association
- Most important simple lipids
- Fatty acids
- Sphingosine
- Cholesterol
- Most important complex lipids
- Cholesteryl esters
- Triacylglycerol (TG)
- Phosphatidylcholine (lecithin)
- Phosphatidylethanolamine (cephalin)
- Sphingomyelin
3
Q
Three Main Lipids
A
- Triacylglycerol
- Main constituent of dietary fats used for energy storage
- Phospholipids
- Major structural component in membranes
- Cholesterol & cholesteryl esters
- Cell membrane components
4
Q
Lipoproteins
- Plasma lipoproteins
- Plasma lipoprotein characteristics
- Lipids in core
- Lipids on surface
A
- Plasma lipoproteins
- Complexes of lipids & proteins
- Classified according to their densities & electrophoretic mobilities
- Plasma lipoprotein characteristics
- Inner droplet of neutral (water-insoluble) core lipids
- Solubilizing surface layer
- Specific proteisn (apolipoproteins) attached to the outer layer through their specific lipophilic domains
- Lipids in core
- Hydrophobic: triacylglycerol (TG), cholesteryl esters (CE)
- Lipids on surface
- Hydrophilic: phospholipids (PL), unesterified cholesterol (UC)
5
Q
Lipoprotein Structure
- General
- Potentially atherogenic lipoproteins contain…
- Potentially protective lipoproteins (HDL) contain…
A
- General
- Water soluble carriers of hydrophobic elements (ex. cholesterol, triglyceride) through the circulatory system
- Potentially atherogenic lipoproteins contain…
- Apolipoprotein B on their surface (B = bad)
- Potentially protective lipoproteins (HDL) contain…
- Apolipoprotein A (A = want to get an A)
6
Q
Lipoprotein Functions
A
- Transport lipid-soluble (water-insoluble) compounds b/n tissues
- Substrates for energy metabolism (TG)
- Essential componetns for cells (PL, UC)
- Precursors for hormones, eicosanoids, & bile acids
- Ex. eicosanoids: thromboxane & prostacyclin
- Lipid soluble vitamins
7
Q
3 Lipoprotein Metabolism Pathways
A
- Exogenous / chylomicron pathway
- Dietary fat
- Characterized by chylomicron mobilization
- Endogenous pathway
- Lipids synthesized by the liver
- HDL metabolism
- Apolipoprotein transfer
- Cholesteryl ester transfer
- Reverse cholesterol transport
8
Q
Exogenous Lipid Metabolism
- Where absorbed cholesterol goes
- Where intestinal cholesterol comes from
A
- Where absorbed cholesterol goes
- Most –> liver via intestinally derived Apo B (48) containing lipoproteins
- Some –> extrahepatic tissues & plaques
- Free –> absorbed via the NPC1L1 transporter mechanism
- Remaining –> eliminated from body
- B/c some biliary cholesterol is reabsorbed & returned to the liver, elimination is incomplete
- Where intestinal cholesterol comes from
- Partially from diet
- Mostly from liver via the biliary system
9
Q
Chylomicrons
- General
- Synthesis
- Functions
- Surface lipoprotein
A
- General
- Largest lipoproteins
- Contain >90% triglycerides
- Synthesis
- Synthesized by the intestine
- Functions
- Transport dietary fat to peripheral tissues for metabolism & storage
- Surface lipoprotein
- Apolipoprotein B (48)
- A = good
- B = bad
- 8 = what you ate
10
Q
Chylomicron Metabolism
A
- Long chain FAs are re-esterified into triglycerides in the gut
- They’re transfered to apoB48 containing chlyomicrons
- These chylomicrons are synthesized in the gut & secreted into the blood via the lymphatic system
- apoC-II activates lipoprotein lipase
- Catalyzes the hydrolysis of the triacylglycerols
- Chylomicron remnant either…
- Is taken back up by the liver via the apoB48 / remnant receptors in the liver
- Can infilitrate hte endothelium & contribute to atherosclerotic plaque formation
11
Q
Endogenous Lipid Metabolism
- Liver & cholesterol
- VLDL remnants
A
- Liver endogenously synthesizes cholesterol
- Liver secretes cholesterol into the circulation via hepatically derived apoB100 lipoproteins
- Liver excretes cholesterol into the intestine as free cholesterol or bile acids via the biliary system
- VLDL remnants (IDL & LDL) are apoB100 containing lipoproteins that can penetrate the arterial endothelium
- LDL is taken up by the lvier by the LDL receptor
12
Q
VLDL
- General
- Biogenesis
- Function
- Metabolism
- Remnant uptake
A
- General
- Contain 60-70% triglycerides
- Biogenesis
- Nascent VLDL particles are assembled in the liver where apoB100 & triglycerides are synthesized
- Function
- Transport endogenously synthesized triglycerides to peripheral tissues
- Metabolism
- apoC-II, apoC-III, apoE, & cholesteryl ester are acquired from HDL in circulation
- apoC-II activates lipoprotein lipase
- Catalyzes the hydrolysis of triglycerides
- FAs, complexed w/ albumin, are transported to muscle for enegy, to adipose tissue for storage, & to liver for further metabolism
- Apolipoproteins are transferred back to the HDL
- Triglyceride poor (cholesterol ester rich) VLDL remants (intermediate density lipoprotein, IDL) is further processed
- Can contribute to the subendothelial atherosclerotic plaque
- Remnant uptake
- VLDL remnant particle (IDL) can be taken up by hepatic apoE / remnatn receptors or can undergo further hydrolysis by hepatic triglyceride lipase to form LDL
13
Q
LDL
- General
- Synthesis
- Function
- Metabolism
- Uptake by tissues
A
- General
- Major cholesterol carrying lipoprotein
- 2/3 to 3/4 of serum cholesterol is carried by LDL
- 50% of mass is cholesterol
- Synthesis
- Produced as a product of VLDL metabolism
- Function
- Delivers cholesterol to peripheral tissues for biosynthesis & steroid hormone production
- Metabolism
- LDL is removed by apoB100 receptors which are mainly expressed in the liver
- Uptake by tissues
- Defects in the LDL receptor –> familial hypercholesterolemia
- Increased nonreceptor mediated uptake of LDL in the liver & non-hepatic tissues
14
Q
A
Tendon Xanthoma
15
Q
A
Corneal Arcus