Cholesterol Flashcards
What is an isoprene?
5C branched chain initiating unit for cholesterol synthesis
What are terpenoids?
Isoprenoid with the presence of ring structures
What is prenylation?
Attachment of farnesyl or geranylgeranyl groups to proteins to anchor them to the membrane
E.g. Ras
Farnesyl = 3 isoprene unites
Geranylgeranyl = 2x 2 isoprene unites
What are some functions of cholesterol?
Stabilize cell membranes
Synthesize bile acids
Synthesize steroid hormones – Vit. D
What is the nucleus of cholesterol?
Steroid 4-ring structure
What two molecules combine to initiate cholesterol synthesis?
Acetoacetyl CoA and acetyl CoA
What is the committed step of Cholesterol formation?
Synthesis of mevalonate via HMG-CoA reductase
What is the role of squalene?
Intermediate in cholesterol synthesis that cyclizes to form the ring nucleus
Converted to cholesterol via many more steps
Under what condition is cholesterol synthesized?
When energy is in excess
What are the four mechanisms of HMG-CoA reductase regulation?
Sterol dependent
Sterol independent
Hormonal regulation
Inhibition by drugs
Describe sterol dependent regulation
SCAP is bound to SREBP on the ER
Proteolytic cleavage via two proteases releases SREBP, which migrates to the nucleus and binds to DNA, initiating transcription of HMG CoA reductase
When cholesterol is present, it prevents migration of SCAP and SREBP to the golgi for processing
Describe sterol independent regulation
Phosphorylation of HMG-CoA reductase inactivates it
Kinase is activated by glucagon, epinephrine, and AMP
What type of drugs affect HMG-CoA reductase and how?
Statins - inhibit HMG-CoA reductase
What is the physiological role of Chylomicrons?
Dietary fat transport
What is the physiological role of VLDL?
Endogenous fat transport
What is the physiological role of IDL?
LDL precursor
What is the physiological role of LDL?
Cholesterol transport
What is the physiological role of HDL?
Reverse cholesterol transport
What is apoprotein B100?
Recognition molecule for the LDL receptor
How are triglycerides and lipoprotein density related?
TG amount decreases as density increases
What are the three isoforms of Apo E?
E2 - rarest form, one copy reduces risk of Alzheimer’s
E3 - most common, no influence
E4 - 20% of population, increases risk for Alzheimer’s
How is cholesterol taken up by tissues?
LDL particle receptor mediated endocytosis
The receptor is a negatively charged glycoprotein concentrated in clathrin pits
How is cholesterol degraded?
Sterol nucleus converted to bile acids
Cholesterol secreted into gall bladder
Used for synthesis of sterol hormones
What is the rate-limiting step in steroid synthesis from cholesterol?
Formation of Prenenolone via Desmolase P450 enzyme
What is formed from prenenolone during steroid synthesis?
Progestagens
