Cholesterol and Sterol Derivatives Flashcards
describe the structure of cholesterol
cholesterol is hydrophobic and consists of 4 hydrocarbon rings, rings ABC are 6 C’s and D is 5 C and there is an 8 C hydrocarbon branched chain attached to D, and there is a hydroxyl group on ring A
what is the structure of sterols?
steroids with 8-10 C on the hydrocarbon side chain and a hydroxyl group are classified as sterols, cholesterol is a major sterol in animal tissues, plant sterols are poorly absorbed in humans
what is plasma cholesterol?
cholesterol in plasma is an esterified form with a FA attached to the -OH group on ring A due to hydrophobicity the cholesterol must be transported with protein in a lipoprotein particle or with phospholipids and a bile salt
what tissues synthesize cholesterol?
liver, intestine, adrenal cortex, reproductive tissues, and brain
describe how cholesterol is synthesized
this occurs in the cytosol with cytosolic enzymes and ER membrane enzymes and begins with the production of HMG-CoA
2 acetyl CoAs are joined via thiolase and 1 CoA leaves forming acetoacetly CoA and this is joined to an acetyl CoA via HMG-CoA (6 Cs)
Next HMG CoA reductase uses NADPH to reduce HMG CoA to mevalonic acid and mevalonic acid is converted to 5-prophophomevaonate in 2 steps that require ATP decarboxylation of pyrophophomevalonate which forms IPP requiring ATP and IPP is isomerized to DPP, which condenses to form GPP, another IPP condenses with GPP and forms 15 carbon FPP, and 2 FPPs combine to form a 30 C compound called squalene, squalene is then converted to cyclic lanosterol and lanosterol is converted tco cholesterol
describe the importance of the phosphorylation that occurs from 5 pyrophosphomevalonic acid to squalene
all these intermediates are phosphorylated, and thus are water soluble, after squalene, a carrier is necessary to keep these intermediates in solution
what is the major control point in cholesterol synthesis?
HMG CoA reductase is rate limiting step
describe the genetic regulation of sterols
expression of HMG CoA reductase is controlled by transcription factor SREBP2, which binds at the sterol regulatory element (SRE), SREBP2 is embedded in the ER membrane and is released via proteolytic cleavage under low cholesterol levels, high cholesterol levels inhibit this cleaveage
how else is HMG CoA reductase affected by cholesterol levels besides genetic regulation?
HMG CoA reductase can be deactivated by a protein kinase (phosphorlyation) or activated by a phosphoprotein phosphatase (desphosphorylation) the kinase is activated by AMP, so cholesterol synthesis decreases with energy decreases
describe hormonal regulation of cholesterol synthesis
HMG-CoA reductase increases with insulin and decreases with glucagon
describe the phamacokinetic regulation of cholesterol synthesis
statin drugs are competitive inhibitors of HMG CoA reductase and lower cholesterol synthesis
describe cholesterol degradation
converted to bile acids and salts because it cannot be converted to CO2 and water and is excreted in the feces, sometimes bacteria assist in modification before excretion
what is cholestanol and coprostanol?
bacteria made cholesterol based compounds for secretion
what are oxysterols?
derived from cholesterol precursors, oxysterols are important regulators of cellular choleserol homeostasis
how does cholesterol get around the BBB?
it cannot, almost all cholesterol is synthesize within the brain
