Riggs Flashcards
MOA of hmg COa reductase inhibitors
Blocks conversion of hmg co a into melavonic acid
MOA of bas
1 removal of bile acids from gi tract via ionic and van der Wals interactions
2 90-95% of bile acids are recycled via enterohepatic loop
3 loss of bile acids means that more has to be made from cholesterol
Enzyme responsible for conversion of hmg COa to melavonate is what?
Hmg COa reductase
Rate limiting
More lipophilic a statin, the what?
Higher risk of myopathy
SAR statin
Business end is dihydroxyacid of statin
Lactone ring can open to the acid form
Acid mimic hmg portion of hmg COa reductase
Other end binds COa binding site, doesn’t occupy all of binding site , to increase affinity target hydrophobic regions and h binding of COa site
MOI is initially slow onset followed by tight competitive inhibition
Indicative of transient state inhibitor
ADR of statins is due to what?
Inhibition of hmg co a and loss of isoprene id intermediates (decreased syn of isoprenylyl pyro phosphate)
Proteins are prenylated by what? Role?
By geranylgeranyl and farnesly groups
Anchor cell signaling enzymes to membrane and or nuclear membrane
If not anchored then no function
Cell signaling enzymes
Ras and rab
Ras and rab
Involved in cell growth
Ras mutation is found in what?
50% of cancers
Pre-lamin a protein
Bound to nuclear membrane
Involved in muscle tissue organization and function
What occurs to post transcription with decreased isoprenoids?
Mod of selenocysteine t RNA is inhibited
Loss of selenoproteins
Results in hepatotoxicity
Dolichol
Biosynthesis from farnsenyl pp
Anchor for sugar units in glycosylated proteins
What happens to coq10 formation due to decreased isoprenoids?
Decrease levels because of decreased isoprenylyl pp
Normal role of coq10
Found in mitochondria
Integral role in electron transport chain
