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Biochemistry- Unit Three
Cholesterol Metabolism (T Pierce)
24
Medical
Post-Graduate
04/16/2009

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Cards

Term
Effect of saturated and unsaturated fat on membrane properties?
Definition
  • saturated fat- more solid membrane
  • unsaturated fat- more fluid membrane
Term
Effect of cholesterol on membrane
Definition
  • essential for membrane function
  • allows the membrane to have a fluid-crystal transition buffer
Term
Define annular lipids
Definition
more structured lipids that form an immovable ring around the membrane due to strong association with membrane bound proteins
Term
Membrane phospholipid that is the backbone for all phospholipids
Definition
phosphatidate
Term
Three major classes of phospholipid attached to polar groups
Definition
  • phosphatidyl serine
  • phosphatidyl ethanolamine
  • phosphatidyl choline
Term
Location of various phospholipids
Definition
  • phosphatidyl ethanolamine and phosphatidyl serine found on inside leaflet of membrane
  • phosphatidyl choline usually on exterior membrane leaflet
Term
How to caspases act on phospholipids
Definition
  • destroys the balance of the various phospholipids on inside and outside
    • may cause equal concentrations of serine/ethanolamine and choline on inside and outside
Term
Process of forming spingolipids
Definition
  1. sphingosine combine with acetyl CoA to form CoA and ceramide
    1. too much ceramide is a very strong signal for apoptosis
  2. Two options
    1. ceramide and UDP glucose form UDP and cerbroside
      1. eventually combine with activated sugars to form gangliosides
    2. ceramide and phosphatidylcholine forms DAG and sphingomyelin
Term
Structure of lipid rafts
Definition
  • rich in saturated FA's
  • much higher proportion of cholesterol in this region
  • lot of semi crystalline phospholipids and sphingolipids
  • many proteins (GF's, TF's) are found in these lipid raft regioins
    • GF's want to bind here and they can become activated
Term
Effect of increase cholesterol on lipid rafts
Definition
  • increase size and number of lipid rafts
  • recruit more proteins in this area (where these proteins shouldnt be)
Term
Process of cholesterol biosynthesis
Definition
  1. synthesis isopentenyl pyrophosphate
  2. condensation of six molecules of isopentenyl pyrophosphate to form squalene
  3. squalene cyclizes
  4. tetracyclic product converted to cholesterol

All carbon atoms from acetyl CoA.

Term
Fate of acetyl CoA and acetoacetyl CoA within the cytosol
Definition
  1. acetyl CoA and acetoacetyl-CoA and water form CoA and 3 HMG CoA
  2. 3 HMG and 3 NADPH's will form NADP and mevalonate via HMG CoA reductase
    1. rate limiting step (site of pharmaceutical intervention)
  3. mevalonate and ATP form                        5-phosphomevalonate
  4. 5 phosphomevalonate and ATP form            5-pyrophosphomevalonate
  5. use ATP and add another phosphate
  6. hydrolyze of CO2 and phosphate to form     3-isopentenyl pyrophosphate
Term
Competitive inhibitor of HMG CoA reductase (statins)
Definition
  • Lovastatin (any analog of 3 HMG-CoA)
  • Pravastatin
  • Simvastatin
  • Fluvastatin
  • Atorvastatin
  • Cerivastatin

Some have fluorine on it to prevent drug from being eliminated via glycosylation, etc. (half life is longer)

Term
 Fate of Dimethyleliyl pyrophosphate and isopentanyl pyrophosphate forming squalene
Definition
  1. dimethylelily pyrophosphate and isopentenyl pyrophoshate make geranyl pyrophosphate
  2. geranyl pyrophosphate combine with isopentenyl pyrophosphate to form farnesyl pyrophosphate
  3. Two farnesyl pyrophosphates combine to form 2 PPi, NADP, H, and squalene
Term
Location of cholesterol synthesis
Definition
ER (this is a membrane based biosynthesis system) (so you make it in the membrane and it modifies membrane fluidity on the spot)
Term
Fate of squalene
Definition
  1. squalene, NADPH, O2 form H2O, NADP, and squalene epoxide
  2. epoxide form protosterol cation
  3. cation form lanosterol
  4. lanosterol undergoes steps to form 2 CO2 and finally cholesterol
Term
Organ that makes cholesterol
Definition

liver (sometimes intestines)

Term
Regulation of cholesterol biosynthesis
Definition
  • rate of synthesis of reductase mRNA
    • control via sterol regulatory element binding protein (SREBP) (if it binds, synthesize gene)
  • rate of translation of reductase mRNA
    • inhibited by nonsteroid metabolites of mevalonate (ex: isoprenoids)
    • dietary cholesterol
  • degradation of reductase
    • via bipartite
      • cytosolic domain carries out catalysis
      • membrane domain senses signals that lead to its degredation
  • phosphorylation decreases activity of reductase (PKA dependent)
Term
Describe SREBP Mech of action
Definition
  1. moves to the Golgi
  2. cut twice
  3. one of the fragments formed is a TF that will allow synthesis of HMG CoA reductase
Term
Role of SCAP (SCREB cleavage activating protein)
Definition
  • SCAP bind cholesterol
  • in presence of cholesterol, SCAP binds SCREBP
  • this causes them to stay in the ER (SCREB cannot be cut, so now we cant make our TF)
Term
Effect of SCAP w/o cholesterol
Definition
  • they are united together, but since the cholesterol is eliminating the structure
  • the two go together to the Golgi, allowing for activation of the TF that makes HMG CoA reductase
Term
chylomicrons (major core lipids, apoproteins, mech. of lipid delivery)
Definition
  • major core lipids- dietary triglycerides
  • apoproteins- B48, E
  • mech. of delivery- hydrolysis by lipoprotein lipase
Term
chylomicron remnant (major core lipids, apoproteins, mechanism of lipid delivery)
Definition
  • major core lipids- dietary CE's
  • apoprotein- B48, E
  • mech. of lipid delivery- receptor mediated endocytosis by liver
Term
Role of flipases and flopases in membrane
Definition
Keep phosphatidylcholine on exterior membrane leaflet and serine/ethanolamide on the interior membrane leaflet
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