MCP Flashcards
clinical correlation: rare, inherited, mutations that encode sterolin transporters, increased phytosterols in blood and tissues, tuberous xanthomas, coronary atherosclerosis
sitosterolemia
clinical correlation: low bile salts or high cholesterol, treat with laproscopic cholesystectomy
cholelithiasis
bile (acids/salts) are better detergents because they are more amphipathic
conjugated ionized bile salts are better detergents
bile salts lost in feces daily is (more than/less than/equal to) the bile salts made daily by liver
equal to
how do statins lower cholesterol
they are structural analogs of HMG and competitively inhibit HMG CoA R-ase, inhibiting cholesterol synthesis
RDS in cholesterol synthesis (substrate, product, enzyme)
HMG CoA to mevalonate by HMG CoA Reductase
8 steps from mevalonate to cholesterol. Number the carbons in each intermediate
mevalonate has 6C > 5PPmevalonate has 6C > IPP has 5C >DMPP has 5C > GPP has 10C > FPP has 15C > squalene has 30C > lanosterol has 30C > cholesterol has 27C
in the synthesis of cholesterol, what is the purpose of release of pyrophosphate
makes reactions irreversible
in the synthesis of cholesterol, what is the purpose of phosphorylation
makes intermediates more soluble in water
which intermediates in synthesis of cholesterol need carrier proteins
squalene, lanosterol, cholesterol
(insulin/glucagon) upregulates HMG CoA R-ase activity
insulin (HMG CoA R-ase=synthesis of cholesterol=anabolic)
(phosphorylation/dephosphorylation) INACTIVATES HMG CoA R-ase
phosphorylation
high cholesterol (increases/decreases) HMG CoA R-ase activity
decreases (binds sterol sensing domain on the enzyme which triggers ubiquitination>proteasomal degradation, also binds sterol sensing domain on SCAP so SCAP-SREBP2 can’t migrate to golgi to cleave SREBP to increase txn)
Apo _: Structural protein (HDL); LCAT activator; Involved in RCT; ligand for ABCA1 and SR-B1
A-I
Apo _: structural protein HDL, inhibits LCAT,
A-II
Apo _: structural protein (VLDL, LDL), VLDL assembly, LDLR binding, one copy for each VLDL
B-100
Apo _: structural protein (LDL, VLDL), VLDL assembly, LDLR binding, produced in intestine, chylomicron metab
B-48
Apo _: can be exchanged freely among lipoprotein particles, important for TG metab bc they interfere with recognition of ApoE by LP receptors or displace ApoE from lipoproteins
C’s
Apo C (I/II/III): LCAT activator
I
Apo C (I/II/III): lipoprotein lipase activator
II
Apo C (I/II/III): inhibits lipoprotein lipase
III
Apo E (2/3/4): normal
3 edited
Apo E (2/3/4): risk for type III hyperlipidemia
3
Apo E (2/3/4): Alzheimer’s
4