Lipids and Lipoproteins

Question 1

gain of function mutatiosn in PCSK9 lead to

Answer 1

reduced LDL receptor levels > high LDL in plasma + increased CHD

Question 1

expressed in spleen, tymus, lung, brain, liver, macrophages, promotes cholesterol efflux to HDL (and not lipid free apaA-1)

Answer 1

ABCG1

Question 1

role of CETP

Answer 1

exchange lipids between LDL and HDL

Question 1

role of Endotehlial lipase

Answer 1

hydrolyzes HDL PLs, > smaller, more-quickly catabolized particles

Question 2

VLDL produced by the ___ when ___

Answer 2

produced by liver when TG production stimualted by influx of FFA or increased de novo synth of FA by liver

Question 2

ACAT 2 found in

Answer 2

intesines and liver

Question 3

role of PCSK9

Answer 3

serine protease that decreases steady state level of LDL receptor expression on hepatocytes >

Question 4

ApoB-48 synthesized by ____, unique to chylomicrons

Answer 4

intestinal epithelial cells

Question 5

most effective way to modulate plasma LDL-C levels

Answer 5

manipulation of hepatic LDL receptor gene expression

Question 5

promotes efflux of cellular phospholipid and cholesterol to lipid free ApoA-1 but not tos pherical HDL

expressed in liver, intestine, macrophages, brain

Answer 5

ABCA1

Question 7

gonad synthesized steroids

Answer 7

progesterone

estrogens

androgens

Question 8

step 3 cholesterol synth

2 isoprenes join to form ____

which joins isopentenyl purophosphate > ___
2 of which join to form ___

Answer 8

2 iosoprenes > geranyl pyrophosphate

+1 isopentenyl purophosphate > farnesyl pyrophosphate

2 of which form > squalene

Question 9

role of ApoC-II

Answer 9

activates lipoprotein lipase to allow FFA release for fuel in aidose, heart and skeletal muscle

Question 10

rate limiting step of cholesterol synth

Answer 10

(in formation of mevalonate)

HMG-CoA + 2NADPH > mevolonate

(as catalyzed by HMG-Coa Reductase)

Question 11

adrenal gland synthesized steriod

Answer 11

mineral corticoids

glucocorticoids

Question 13

store form of cholesterol

Answer 13

cholesteryl esters

Question 14

role of ABCG5 ABCG8, on apical PM of enterocytes

Answer 14

export plant sterols back into intestinal lumen

Question 15

endocytosis of depleted chylomicron remants requires ___ as a ligand for hepatic receptors like LDL receptor and LRP

Answer 15

apoE

Question 16

synthesized in liver, delivers TG to tissues as FA via lipoprotein lipases

Answer 16

VLDL

Question 17

______ is required for delivery of FA derived from TG of chylomicrons and VLDL to tissues

Answer 17

Lipoprotein lipase mediated hydrolysis (LPL)

Question 18

impact on HL expression, estrogens and androgens

Answer 18

androgens increase HL acivity

estroens reduces

Question 19

___ and ___ enahnce LDL receptor gene expression, leading to LDL-C lowering

Answer 19

thyroixine and estrogen

Question 20

role of PLTP

Answer 20

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

Question 21

4 steps of cholesterol synth

Answer 21

1) 3 acetate > (6C) mevalonate
2) phosphorylated 5-C isoprene
3) (30C) Squalene
4) Squalene cyclizes > 4 ringed cholesterol

Question 22

pts with dysfxnl MTP fail to make

Answer 22

Chylomicrons, VLDL, LDL

(any of the apoB containing lipoproteins)

Question 22

most abundant proteins on HDLs

Answer 22

ApoA-1

ApoA-II

Question 23

activate transcription of HMG-CoA reductase and LDL receptor when cellular sterol levels decrease

Answer 23

SREBPs

Question 25

esterfies free cholesterol to form cholestryl esters

Answer 25

ACAT

Question 27

TG transfer by ____ to site where newly synthesized apoB-100 is available to form new VLDL

Answer 27

microsomal triglyceride transfer protien (MTP)

Question 28

monophospholipid monolayer covering surface of lipoproteins

Answer 28

apolipoproteins

Question 28

backup receptor responsible for apoE-enriched remants of chylomicrons and VLDL

Answer 28

LDL receptor reated protein (LRP)

Question 29

apolipoprotein roles

Answer 29

help solubolize lipoprotein in circulation

activate or inhibit plasma enzymes

ligands for cell surface receptors

Question 30

2 fates of VLDL remnants

Answer 30

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)

Question 31

role of NPCL1

Answer 31

mediates intestinal cholesterol absorption

Question 33

because TG is removed, LDL (from VLDL) is enriched in

Answer 33

cholesterol and cholesteryl esters

Question 34

mutations, pathology of sitosterolemia

Answer 34

mutation of ABCG5 and ABCG8

over absorption of of plant sterols, failure to secret sterols into bile

tendon+subQ xanthomas, increased risk of CHD

Question 35

cholesterol converted to bile acids via pathway intiated by

Answer 35

cholesterol 7a-hydroxylase

Question 36

during prolonged fasting and diabetic ketoacidosis, ____ of adipose tissue falls

Answer 36

LPL activity - preventing storage of FAs

Question 37

mutation in Tangier disease

Answer 37

loss of function in ABCA1 > low levels of HDL and CE accumulation

Question 37

ABCA1 mediated transfer of phospholipid and FC to apoA-1 results in formation of

Answer 37

nascent HDL (pre betaHDL)

Question 38

lipoprotein lipase LPL is activated by

Answer 38

presence of apoC-II on CMs and VLDL

Question 39

___ is a cofactor for LPL > when given IV, LPL activity is displaced into plasma, allowing its measurement

Answer 39

Heparin

(Apo- C-II is also an abligatory cofactor)

Question 41

role SR-BI

Answer 41

HDL receptor

in liver, ovaries, testes, adrenalglands

Question 42

ACAT 1 found in

Answer 42

macrophages (including foam cells, adrenocoritcal cells, sebaceous glands)

Question 43

interior of lipoproteins contain

Answer 43

cholesterol

TG

choelsteryl esters