2. Introduction to Lipids and Lipoprotein Metabolism (Part I) Flashcards
What is the endogenous source of body cholesterol? Which cells are capable of making cholesterol?
- De novo synthesis from Acetyl-CoA
- All cells in the body are capable of making cholesterol
What are exogenous sources of cholesterol?
- Diet
- Dietary sources are really “excess” cholesterol, as all cells can make cholesterol
What justifies that there is an important need for cholesterol?
- Cholesterol is a very energetically expensive molecule
- But, it cannot be oxidized (can’t get ATP back)
What are statins?
Class of drugs that are competitive inhibitors of HMG-CoA reductase
What metabolites does the synthesis of cholesterol produce?
- Various
- They are not solely dedicated to the synthesis of cholesterol
What happens in liver cells after HMG-CoA reductase makes cholesterol?
Cholesterol is released into the blood by hepatocytes
How do statin drugs work?
- Inhibit HMG-CoA reductase by competing with its natural substrate (HMG-CoA)
- Cholesterol synthesis is blocked, lowering levels of cholesterol
How do statins vary?
They look very different, but they are all capable of inhibiting the activity of HMG-CoA reductase
What did this study discover: “Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks of clusters of risk”?
- Child and maternal malnutrition and dietary risks are among the highest risk factors for metabolic disorders
- Cardiovascular diseases, neoplasms, diabetes
- Ample evidence for causation, but people still abuse of certain foods
What transports TG through the bloodstream?
Chylomicrons
Where are certain fatty acids used?
Muscles, liver, heart
What happens when the liver receives TG?
- Repackages it
- TG are transported through the bloodstream via VLDL
What are the two functions of bile acids?
- Emulsification of fats and fat-soluble nutrients
- Activator of bile-salt activated lipase
Where are bile acids found? Where are lipases found?
- Bile acids: small and large intestines
- Lipases: small intestine
What is the function of lipases? Be specific.
Digestion of lipids acquired from the diet (cholesteryl esters, acylglycerols, phospholipids)
What are the four steps to the conversion of cholesterol to bile acids?
- Hydroxylation of the steroid nucleus
- Epimerization of the 3-Beta hydroxyl group
- Saturation of the steroid nucleus
- Side chain cleavage
What happens overall when cholesterol is converted to bile acids?
- Converts the shape of cholesterol from chair-type to a more flat configuration, rendering it POLAR
- Bile acids are amphipathic
- Charged functional groups are on one face of the molecule, uncharged are unable to act with water
Describe the fate of diet-derived lipids in the lumen, when they are absorbed, and they are resynthesized in enterocytes.
- TG –>FA + MG –> TG
- CE –> CH + FA –> CE
- PC –> LysoPC + FA –> PC
- They will bind to transporters for absorption, and will be reassembled in the enterocytes
What is the function of phospholipases?
Breaking down a phospholipid to give you a lysophopholipid and a fatty acid
What transporter brings in free cholesterol?
NPC1L1
What transporters bring in free fatty acids?
- FATP4
- CD36
What transporter is thought to bring in free phospholipids?
MFSD2A
Why are we selective concerning absorption of nutrients?
Because absorption of dietary lipids requires SPECIFIC membrane-bound transporters that are on the surface of enterocytes
Where does the ER process lipids?
- In a specialized compartment in the cell because it is hydrophobic
- In the lumen of ER
What is ACAT? What is its function?
- Lipid-metabolizing enzyme
- Acyl:cholesterol acyl transferase
- Responsible for creating cholesteryl esters from cholesterol in cells
What is MTP? What is its function?
- Lipid carrier protein
- Microsomal triglyceride transfer protein
- Exists at junctions of the ER and other organelles that are involved in the assembly of chylomicrons
Which protein is involved in the assembly of chylomicrons?
MTP
Which enzyme is responsible for creating cholesteryl esters from cholesterol?
ACAT
What are lipoproteins?
Non-covalent complexes of lipids and proteins
Without ______, we can’t form HDL.
Apo A-I
What is Apo B-100 responsible for?
- Extremely large
- Only 48% (from the N-terminal) is found in chylomicrons
- The remaining 52% (C-terminus) is responsible for limiting the size of VLDL-like proteins
What do you need to remove from Apo B-100 to allow the size of the lipoprotein to increase?
52% of Apo B-100 from the C-terminus
What is LCAT?
- Activator of the LCAT enzyme
- Esterifies the cholesterol with a fatty acid in blood (becomes cholesteryl esters)
Differentiates LCAT and ACAT.
- LCAT: creates cholesteryl esters in blood from cholesterol
- ACAT: creates cholesteryl esters in cells from cholesterol
What is particular about Apo E?
- Exchangeable protein
- It can jump to any of the other lipoproteins
Which apolipoprotein can be taken away without affecting their structure?
Apo E
Which lipoproteins are related to Apo A-I? What is their function?
- CM, HDL
- Structure, LCAT activator
Which apolipoproteins serve as an LCAT activator?
Apo A-I, Apo A-IV
Which lipoproteins are related to Apo A-II?
CM and HDL
Which lipoproteins are related to Apo A-IV? What is their function?
- CM, HDL
- LCAT activator
- Satiety?
Which lipoproteins are related to Apo B-48? What is their function?
- CM
- Structure of CM
Which lipoproteins are related to Apo B-100? What is their function?
- VLDL, IDL, LDL
- Structure
- VLDLR and LDLR ligand
Which lipoproteins are related to Apo C and Apo E lipoproteins?
CM, VLDL, IDL, LDL
Which apolipoprotein serves as a lipoprotein lipase activator?
Apo C-II
Which apolipoprotein serves as a lipoprotein lipase inhibitor?
Apo C-III
Which apolipoproteins serve as a ligand for LDLR and VLDLR?
- Apo B-100
- Apo E