• saturated fat- more solid membrane
• unsaturated fat- more fluid membrane

• essential for membrane function
• allows the membrane to have a fluid-crystal transition buffer

• phosphatidyl serine
• phosphatidyl ethanolamine
• phosphatidyl choline

• phosphatidyl ethanolamine and phosphatidyl serine found on inside leaflet of membrane
• phosphatidyl choline usually on exterior membrane leaflet

• destroys the balance of the various phospholipids on inside and outside
  • may cause equal concentrations of serine/ethanolamine and choline on inside and outside

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

• 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

• increase size and number of lipid rafts
• recruit more proteins in this area (where these proteins shouldnt be)

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.

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

• 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)

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

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

liver (sometimes intestines)

• 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)

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

• 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)

• 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

• major core lipids- dietary triglycerides
• apoproteins- B48, E
• mech. of delivery- hydrolysis by lipoprotein lipase

• major core lipids- dietary CE's
• apoprotein- B48, E
• mech. of lipid delivery- receptor mediated endocytosis by liver