Lipoprotein Biochemistry - Sahoo Flashcards
What’s the difference between a simple and mixed triglyceride? Which is more common in nature?
Simple TGs: Same fatty acid in all 3 positions. Mixed TGs: 2 or 3 different fatty acids. Most naturally-occurring TGs are Mixed.
What can an elevated TG level predict independent of other risk factors?
-Risk of CV disease -Pancreatitis if several elevated (>1000mg/dL)
Name 5 functions of cholesterol.
1) Essential cell membrane component 2) Important and enriched in lipid rafts 3) Reduces membrane fluidity* 4) Precursor for bile acids and steroid hormones 5) Covalent modification of embryonic signaling proteins *From what I can find, this helps make the cell membrane a little more structurally rigid (in a good way), and makes it less permeable to small water-soluble compounds that would otherwise diffuse into the cell.
Name 5 classes of compounds derived from cholesterol and at least one specific compound in each class.
1) Androgens - Androsterone, Testosterone 2) Estrogens - Estradiol, Estriol, Estrone 3) Mineralocorticoids - Aldosterone, Corticosterone 4) Glucocorticoids - Cortisol 5) (Primary & Secondary) Bile Acids - Cholic acid (1°), Deoxycholic acid (2°)
Name 5 ways in which excessive cholesterol is cytotoxic.
1) Cholesterol crystal formation 2) Triggering apoptotic pathways 3) Forming toxic oxysterols 4) Disruption of functional & signaling membrane domains 5) Promotes atherosclerosis
Name the 4 major steps of cholesterol synthesis and the number of carbon atoms in each major compound
1) 3x Acetate (2C) –> Mevalonate (6C) 2) Mevalonate –> phosphorylated Isoprene (5C) 3) 6x Isoprene –> Squalene (30C) 4) Squalene –> Cholesterol (27C)
Name 3 substeps in the formation of mevalonate from acetyl-CoA and the enzymes that catalyze them.
1) 2 Acetyl-CoA → Acetoacetyl-CoA
* via acetyl-CoA acyl transferase*
2) Acetoacetyl-CoA + Acetyl-CoA → HMG-CoA
* via HMG-CoA synthase*
3) HMG-CoA + 2 NADPH → Mevalonate
* via HMG-CoA reductase**
** **Rate-Limiting Step of Cholesterol Synthesis
Name 3 substeps in the conversion of mevalonate to isoprene.
1) Stepwise transfer of 3 PO43- from ATP to mevalonate.
2) Decarboxylation and hydrolysis forms the 5C isoprene
- Introduces a double bond
3) There are actually 2 isoprenes, which can isomerize back and forth
- Difference is location of double bond
Name 3 substeps in the formation of squalene from isoprene units.
1) 2 isoprene → geranyl pyrophosphate
* -one of each isoprene isomer is needed*
2) geranyl pyrophosphate + isoprene → farnesyl pyrophosphate
3) 2 farnesyl pyrophosphate → squalene
* -squalene is phosphate-free*
Name 3 substeps in the conversion of squalene to cholesterol and the enzymes that perform each step.
1) squalene + NADPH + O2 → squalene 2,3-epoxide
* via squalene monooxygenase*
2) squalene 2,3-epoxide → lanosterol
* via cyclase*
3) lanosterol → cholesterol
* multistep - specifics not listed*
Where does cholesterol synthesis diverge between animals and plants and fungi?
The fate of squalene 2,3-epoxide differs.
Animal: Lanosterol → Cholesterol
Plants, Fungi: Stigmasterol, Ergosterol
1) Where is most cholesterol synthesized in the body?
2) In what forms?
3) What forms are later converted from cholesterol in other tissues?
1) Liver
2) Bile acids, Biliary Cholesterol, Cholesteryl Esters
3) Other tissues form steroid hormones, some others
How do bile acids work?
They surround fat droplets and help to emulsify them. This increases the surface area available for attack by lipases.
Which are more non-polar: cholesterol or cholesterol esters? What is a consequence of this?
Cholesterol esters. The added hydrophibicity makes then unable to enter membranes.
Which LP class contains the most:
1) Protein
2) Phospholipids
3) Free Chol
4) Chol esters (CEs)
5) TGs
1) Protein: HDL
2) Phospholipids: HDL
3) Free Chol: VLDL/LDL
4) Chol esters (CEs): LDL
5) TGs: Chylomicrons
What is the surface of a lipoprotein particle composed of?
What is the interior composed of?
Surface: apolipoproteins, phospholipid monolayer
Interior: cholesterol, cholesterol esters, TGs
A lipoprotein’s density is [directly, inversely] related to its size.
Inversely
Name the major subclasses of lipoproteins in order of increasing density.
1) Chylomicrons
2) VLDLs
3) VLDL remnants
4) IDLs
5) LDLs
6) Lp(A)
7) HDLs
Name the identifying apolipoprotein (apoLP) and a major function/characteristic of:
1) Chylomicrons
2) VLDLs
3) IDLs
4) LDLs
5) Lp(A)
6) HDLs
1) Chylomicrons: apoB-48, C, E; delivers chol & TGs from gut to tissues & liver
2) VLDLs: apoB-100, C, E; made in liver and delivers TG to tissues as fatty acids
3) IDLs: apoB-100, some C, E; short-lived LP between VLDL and LDL
4) LDLs: apoB-100 ONLY; stays in circulation longest
5) Lp(A): apo(a), apoB-100; an odd LDL-like particle - apo(A) is structurally sim(ilar to plasminogen
6) HDLs: apoA-I & apoA-II, C, E; generally good
Which LP class contains the least:
1) Protein
2) Phospholipids
3) Free Chol
4) Chol esters (CEs)
5) TGs
1) Protein: Chylomicrons
2) Phospholipids: Chylomicrons
3) Free Chol: Chylomicrons/HDL
4) Chol esters (CEs): Chylomicrons
5) TGs: HDL
Name 4 functions of apolipoproteins.
1) Help solubilize the LP particle in the circulation
2) Change conformation to adjust to changing lipid contents, compositions, and metabolic states
3) Can activate or inhibit plasma enzymes
4) Serve as ligands for cell surface receptors
Name the function(s) of:
1) ApoA-I
2) ApoA-II
3) ApoB-48
4) ApoB-100
1) ApoA-I: Activates LCAT, interacts with ABC transporter
2) ApoA-II: Inhibits LCAT, structural
3) ApoB-48: Chol & TG transport and clearance
4) ApoB-100: Binds LDL receptor to deliver endogenous chol
Which ApoLPs are most strongly associated with
1) increased risk of atherosclerosis?
2) decreased risk of atherosclerosis?
Increased risk: apoB-100, apo(a)
Decreased risk: apoA-I
How are triacylglycerols taken up by the gut? Where is this process mirrored?
In short, they are broken down, absorbed, then reformed.
In detail: bile salts emusify the fats, forming mixed micelles that are attacked by lipases. The lipases degrade TGs into fatty acids (FAs), which are taken up by the mucosa and converted back into TGs.
The process is mirrored in the capillaries: LP lipase converts TGs into FAs + glycerol, which are taken up by cells. Cells can resesterify these back into TGs (or utilize them as fuel).
