Lipids and Lipoproteins Flashcards
gain of function mutatiosn in PCSK9 lead to
reduced LDL receptor levels > high LDL in plasma + increased CHD
expressed in spleen, tymus, lung, brain, liver, macrophages, promotes cholesterol efflux to HDL (and not lipid free apaA-1)
ABCG1
role of CETP
exchange lipids between LDL and HDL
role of Endotehlial lipase
hydrolyzes HDL PLs, > smaller, more-quickly catabolized particles
VLDL produced by the ___ when ___
produced by liver when TG production stimualted by influx of FFA or increased de novo synth of FA by liver
ACAT 2 found in
intesines and liver
role of PCSK9
serine protease that decreases steady state level of LDL receptor expression on hepatocytes >
ApoB-48 synthesized by ____, unique to chylomicrons
intestinal epithelial cells
most effective way to modulate plasma LDL-C levels
manipulation of hepatic LDL receptor gene expression
promotes efflux of cellular phospholipid and cholesterol to lipid free ApoA-1 but not tos pherical HDL
expressed in liver, intestine, macrophages, brain
ABCA1
gonad synthesized steroids
progesterone
estrogens
androgens
step 3 cholesterol synth
2 isoprenes join to form ____
which joins isopentenyl purophosphate > ___
2 of which join to form ___
2 iosoprenes > geranyl pyrophosphate
+1 isopentenyl purophosphate > farnesyl pyrophosphate
2 of which form > squalene
role of ApoC-II
activates lipoprotein lipase to allow FFA release for fuel in aidose, heart and skeletal muscle
rate limiting step of cholesterol synth
(in formation of mevalonate)
HMG-CoA + 2NADPH > mevolonate
(as catalyzed by HMG-Coa Reductase)
adrenal gland synthesized steriod
mineral corticoids
glucocorticoids
store form of cholesterol
cholesteryl esters
role of ABCG5 ABCG8, on apical PM of enterocytes
export plant sterols back into intestinal lumen
endocytosis of depleted chylomicron remants requires ___ as a ligand for hepatic receptors like LDL receptor and LRP
apoE
synthesized in liver, delivers TG to tissues as FA via lipoprotein lipases
VLDL
______ is required for delivery of FA derived from TG of chylomicrons and VLDL to tissues
Lipoprotein lipase mediated hydrolysis (LPL)
impact on HL expression, estrogens and androgens
androgens increase HL acivity
estroens reduces
___ and ___ enahnce LDL receptor gene expression, leading to LDL-C lowering
thyroixine and estrogen
role of PLTP
catalyzes transfer of PL between lipoprotein classes
needed for maximal activity of mCAT
major role in generating pre-BHDL
promotes PL efflux to preformed HDL
4 steps of cholesterol synth
1) 3 acetate > (6C) mevalonate
2) phosphorylated 5-C isoprene
3) (30C) Squalene
4) Squalene cyclizes > 4 ringed cholesterol
pts with dysfxnl MTP fail to make
Chylomicrons, VLDL, LDL
(any of the apoB containing lipoproteins)
most abundant proteins on HDLs
ApoA-1
ApoA-II
activate transcription of HMG-CoA reductase and LDL receptor when cellular sterol levels decrease
SREBPs
esterfies free cholesterol to form cholestryl esters
ACAT
TG transfer by ____ to site where newly synthesized apoB-100 is available to form new VLDL
microsomal triglyceride transfer protien (MTP)
monophospholipid monolayer covering surface of lipoproteins
apolipoproteins
backup receptor responsible for apoE-enriched remants of chylomicrons and VLDL
LDL receptor reated protein (LRP)
apolipoprotein roles
help solubolize lipoprotein in circulation
activate or inhibit plasma enzymes
ligands for cell surface receptors
2 fates of VLDL remnants
cleared from plasma by liver via LDL receptors and LRP
LPL and Hepatic lipase convert to LDL by removal of additional TG (virtually all LDL particles are derived from VLDL)
role of NPCL1
mediates intestinal cholesterol absorption
because TG is removed, LDL (from VLDL) is enriched in
cholesterol and cholesteryl esters
mutations, pathology of sitosterolemia
mutation of ABCG5 and ABCG8
over absorption of of plant sterols, failure to secret sterols into bile
tendon+subQ xanthomas, increased risk of CHD
cholesterol converted to bile acids via pathway intiated by
cholesterol 7a-hydroxylase
during prolonged fasting and diabetic ketoacidosis, ____ of adipose tissue falls
LPL activity - preventing storage of FAs
mutation in Tangier disease
loss of function in ABCA1 > low levels of HDL and CE accumulation
ABCA1 mediated transfer of phospholipid and FC to apoA-1 results in formation of
nascent HDL (pre betaHDL)
lipoprotein lipase LPL is activated by
presence of apoC-II on CMs and VLDL
___ is a cofactor for LPL > when given IV, LPL activity is displaced into plasma, allowing its measurement
Heparin
(Apo- C-II is also an abligatory cofactor)
role SR-BI
HDL receptor
in liver, ovaries, testes, adrenalglands
ACAT 1 found in
macrophages (including foam cells, adrenocoritcal cells, sebaceous glands)
interior of lipoproteins contain
cholesterol
TG
choelsteryl esters
