Cholesterol and Serol Derivatives Flashcards
describe the structure of cholesterol
hydrophobic compound consisting of four hydrocarbon rings. “steroid nucleus”
rings A, B, and C are 6 carbon rings, while ring D is 5 carbon
there is an eight carbon hydrocarbon branched chain attached on ring D, and theres a hydroxyl group on ring A
what is the structure of sterols?
steroids w/ 8-10 C on the hydrocarbon side chain and a hydroxyl group are classified as sterols. cholesterol is the major sterol in animal tissues.
plant sterols are poorly absorbed in humans
what is plasma cholesterol?
cholesterol in plasma is in an esterified form, with a fatty acid attached to the hydroxyl group on ring A.
d/t hydrophobicity, cholesterol must be transported w/ protein in a lipoprotein particle, or w/ phospholipids and bile salts
what tissues synthesize cholesterol
liver, intestine, adrenal cortex, reproductive tissues, and brain
describe the cholesterol synthesis pathway
occurs in the cytosol, w/ cytosolic enzymes and ER membrane enzymes. begins with the production of HMG-CoA
2 Acetyl CoAs are joined via thiolase, and 1 CoA leaves forming Acetoacetyl-CoA
Acetoacetyl-CoA is joined to Acetyl-CoA via HMG-CoA (6 carbon)
next, HMG CoA reductase uses NADPH to reduce HMG CoA to Mevalonic acid
Mevalonic acid is converted to 5-pyrophosphomevalonate in 2 steps that require ATP
decarboxylation of pyrophosphomevalonate forms 5-C isopentenyl pyrophosphate (IPP) (requires ATP).
IPP is iosomerized to DPP
IPP and DPP condense to form GPP (10-C)
Another IPP condenses w/ GPP forms 15-C FPP
2 FPPs combine, forming a 30-C compound squalene
Squalene is converted to cyclic lanosterol
lanosterol is converted to cholesterol
describe the importance of the phosphorylation that occurs from 5-pyrophophomevalonic 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 the synthesis of cholesterol synthesis?
HMG CoA reductase is the rate limiting enzyme
describe genetic regulation of sterols
expression of HMG CoA reductase is controlled by the transcription factor SREBP2, which binds at the sterol regulatory element (SRE).
SREBP2 is embedded in the ER membrane, but is released via proteolytic cleavage under low cholesterol levels. high cholesterol levels inhibit this cleavage
independent of genetic regulation, how else is HMG CoA reductase affected by cholesterol levels
increased cholesterol decreases the stability of HMG CoA reductase
describe the regulation via AMP of cholesterol
HMG CoA reductase is can be deactivated by a protein kinase (phosphorylation), or activated by phosphoprotein phosphatase (dephosphorylation). the kinase is activated by AMP, so cholesterol synthesis decreases w/ energy decreases
describe hormonal regulation of cholesterol synthesis
HMG CoA reductase increases w/ insulin and decreases w/ glucagon
describe pharmacokinetic regulation of cholesterol synthesis
stain drugs (simvastatin, lovastatin, and mevastatin) are competitive inhibitors of HMG CoA reductase and lower cholesterol synthesis
describe cholesterol degradation
converted to bile acids and salts b/c cannot be converted to CO2 and H2O. excreted w/ feces. sometimes bacteria help by modifying before excretion
cholestanol and coprostanol
bacteria made cholesterol based compounds for excretion
oxysterols
derived from cholesterol precurors, oxysterols are important regulators of cellular cholesterol homeostasis
