Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Scientific Foundations > Lecture 53 > Flashcards

Lecture 53 Flashcards

Lipoproteins: Structure, Function, and Metabolism

1
Q

lipoproteins overview and classes

A
  • spherical macromolecular complexes of lipids and specific proteins (apolipoproteins)
  • their role is to transport cholesterol, fats, and fat-soluble compounds via the blood (all hydrophobic so need protein carriers)
  • 4 major classes: chylomicrons, very low density (VLDL), low density (LDL), and high density (HDL)

pg 1373-1374

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

lipid transport in the blood

A
  • as part of lipoproteins: triacylglycerols, phospholipids, steroids (cholesterol), and sphingolipids
  • bond to serum albumin: free fatty acids

pg 1375

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

cholesterol

A
  • free cholesterol: maintains fluidity in membranes
  • cholesterol ester: storage and transport form

pg 1376

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

lipoprotein core

A
  • composed of hydrophobic neutral lipids:
  • triacylglycerols (TAGs)
  • cholesterol esters (CE)

pg 1377

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

lipoprotein polar lipid surface

A
  • composed of a monolayer of amphipathic lipids:
  • phospholipids (phosphatidylcholine - PC and sphingomyelin - SM)
  • unesterified (free) cholesterol -> fluidity
  • polar head likes water, 2 hydrophobic FA tails face core

pg 1378

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

lipoprotein amphipathic apolipoproteins (Apo)

A
  • more than 11 different types of Apo proteins found in humans (ApoA, ApoB, ApoC, ApoD, etc)
  • several subclasses of each type of Apo protein
  • peripheral and integral

pg 1379

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

apolipoproteins in humans

A

from this slide -> Apo B

  • Apo B-48 from intestine, associated with chylomicrons, structural protein for chylomicrons
  • Apo B-100 from liver, associated with VLDL, IDL, LDL -> structural protein, ligand for LDL receptor

pg 1380

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

lipid composition and size of lipoproteins

A
  • chylomicrons biggest, but least dense
  • HDL smallest, but most dense

pg 1381

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

chylomicrons

A
  • size may vary depending on meal content
  • largest in size, least dense
  • contain highest percentage of fat (90%)
  • produced by gut cells

pg 1382

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

VLDL

A
  • similar to chylomicrons, but produced by hepatocytes
  • smaller and more dense
  • contain a high percentage of fat reflecting their primary role to distribute fat away from the liver to peripheral tissues
  • 20% cholesterol

pg 1382

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

LDL

A
  • contain highest percentage of cholesterol (50%)
  • reflects their role to distribute cholesterol to tissues
  • produced from VLDL via lipolysis in the bloodstream

pg 1382

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

HDL

A
  • highest percentage of protein (40%)
  • reflects one of the roles as a reservoir of Apo-s
  • second highest percentage of cholesterol reflective of their role in the reverse cholesterol transport
  • capable of exchanging Apo proteins with other lipoproteins
  • “good cholesterol”
  • take up all excess cholesterol and take back to liver for removal

pg 1383

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

understanding lipid lab values

A
  • total cholesterol: cholesterol attached to lipoproteins (chylomicrons, VLDL, LDL, IDL, HDL)
  • triglycerides: chylomicrons, VLDL, IDL
  • HDL cholesterol: HDL only
  • CHOL/HDL ratio: total cholesterol divided by HDL
  • LDL calculated (lipid panel): total cholesterol minus HDL and VLDL
  • direct LDL cholesterol: measured
  • VLDL cholesterol: VLDL only

pg 1384

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

exogenous lipoprotein metabolism

A
  • gut forms nascent chylomicron (initial large molecule released into lymph)
  • lipoprotein lipase in circulation converts to chylomicron
  • chylomicron goes through circulation and leaves chylomicron remnant behind (what is left after delivering lipids to peripheral tissues)
  • chylomicron remnant goes to liver
  • ALSO: HDL collects cholesterol from tissues, undergoes Apo exchange with chylomicrons, delivers cholesterol to liver

pg 1385

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

endogenous lipoprotein metabolism

A
  • liver produces VLDL
  • VLDL in body becomes IDL and then LDL
  • IDL and LDL go to tissues and eventually back to liver
  • HDL participates in reverse cholesterol transport (RCT) -> collects excess cholesterol from peripheral tissues

pg 1386

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

metabolism of chylomicrons

A
  1. intestinal mucosal cells secrete nascent TAG-rich chylomicrons produced from dietary (exogenous) lipids -> has apo B-48

pg 1387

17
Q

production of chylomicrons and VDL: step 1

A

synthesis of Apo B

  • B-apolipoprotein gene undergoes transcription and RNA editing to form Apo B-100 and Apo B-48
  • Apo B-100 (full length) formed in liver hepatocytes to produce VLDL
  • Apo B-48 (48% of length) formed in intestine due to early stop codon -> packages lipids from diet (in enterocytes) into chylomicrons

pg 1388

18
Q

production of chylomicrons and VDL: step 2

A

Co-translational lipidation of Apo B

  • lipids from enterocyte cross ER membrane via microsomal TAG-transfer protein (MTP) to join Apo B-48 and form the Apo B particle
  • triacylglycerols also use MTP to join Apo B particle and form larger Apo B particle

pg 1389

19
Q

lomitapide (Juxtapid)

A
  • small molecule inhibitor of MTP that has been approved for the treatment of certain patient populations
  • population: individuals that are homozygous for mutations in the LDL receptor and are not effectively treated with drugs such as alirocumab and statins

pg 1389

20
Q

production of chylomicrons and VDL: step 3

A

maturation and secretion

  • in the right conditions, the larger Apo B particle leaves the endoplasmic reticulum and goes to the golgi apparatus
  • when perfectly lipidated and packaged, it is secreted into the blood stream
  • if missing something OR not the right size and shape, it will undergo lysosomal degradation

pg 1390

21
Q

abetalipoproteinemia (Bassen-Kornzweig syndrome)

A
  • defect in the microsomal TAG-transfer protein (MTP)
  • autosomal recessive -> rare
  • near complete absence of the apo B-containing lipoproteins
  • affects the absorption of dietary fats, cholesterol, and fat-soluble vitamins

pg 1391

22
Q

abetalipoproteinemia symptoms

A
  • appear in the first few months of life
  • failure to gain weight and grow at the expected rate
  • diarrhea
  • abnormal star-shaped red blood cells
  • fatty, foul-smelling stools that may contain large chunks of fat and/or blood
  • later in childhood -> impairment of the CNS function, poor muscle coordination, progressive retina degeneration to near-blindness (due to deficiency of vitamin A, retinol)

pg 1391

23
Q

metabolism of chylomicrons pt 2

A

part of exogenous pathway
step 2. apo C-II and apo E are transferred from HDL to the nascent chylomicron (now has apo B-48, C-II, and E)
step 3. extracellular lipoprotein lipase, activated by apo C-II, degrades the TAG in chylomicrons
step 4. apo C-II is returned to HDL
step 5. CE-rich chylomicron remnants bind through apo E to specific receptors on the liver and are endocytosed

pg 1392

24
Q

metabolism of VLDL, IDL, and LDL

A

part of endogenous pathway
1. liver secrete nascent, TAG-rich VLDL particles containing primarily endogenously synthesized lipids
2. apo C-II and apo E are transferred from HDL to the nascent VLDL
3. extracellular lipoprotein lipase, activated by apo C-II, degrades the TAG in VLDL (now IDL)
4. apo C-II and apo E are returned to HDL (removed from IDL) -> some IDL with apo E attached goes back to liver
5. LDL binds to specific receptors on extrahepatic tissues and on the liver and are endocytosed

pg 1393

25
Q

fibrates

A
  • used to lower TAG levels
  • act through PPARα to…
  • increase the expression of LPL (lipoprotein lipase)
  • decrease apo C-III concentration
  • increase HDL by increasing the expression of apo A-I and apo A-II

pg 1393

26
Q

familial hyperchylomicronemia (Burger-Grutz syndrome)

A
  • deficiency of lipoprotein lipase (LPL)
  • autosomal recessive
  • more common in areas of the province of Quebec
  • symptoms: elevated plasma TAGs even in the fasted state, xanthomas (skin depositions of lipid), and pancreatitis

pg 1394

27
Q

hyperproteinemia type III (broad beta disease)

A
  • there are three common isoforms of apo E in humans -> apo Ee2, apo Ee3, and apo Ee4
  • caused by homozygosity for apo Ee2, a genetic variant that does not bind to hepatic apo E receptors
  • autosomal recessive
  • symptoms: chylomicron remnants and IDLs remain in blood, elevating both, TAGs and cholesterol; xanthomas and early cardiovascular disease are common

pg 1395

28
Q

metabolism of HDL

A

see slide

pg 1396,1398

29
Q

LCAT role in metabolism of HDL

A

lecithin:cholesterol acyltransferase (LCAT)

  • synthesized and secreted by the liver
  • acts in the circulation to transfer of a fatty acid from the 2-position of lecithin (phosphatidylcholine, PC) in the phospholipid shell of the HDL particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester
  • necessary in order to trap the cholesterol ester to the core of the HDL particle

pg 1397

30
Q

CETP role in metabolism of HDL

A

CETP (cholesterol ester transfer protein) -> acts to simultaneously transfer TAGs from VLDL/IDL to HDL and cholesterol esters from HDL to VLDL/IDL

  • the greater the concentration of triacylglycerol-rich lipoproteins in the blood, the greater the rate of these exchanges
  • the CETP reaction, under high levels of TAG-rich lipoproteins, generates elevated levels of HDL3, which are leass atheroprotective than HDL2
  • CETP inhibitors are currently being evaluated as a means of increasing HDL2 levels, with limited success

pg 1399

31
Q

Tangier disease

A
  • defect of the ABCA1 protein
  • autosomal recessive
  • very rare
  • symptoms: significantly reduced HDL, mild hypertiglyceridemia, disturbances in nerve function (neuropathy) and enlarged, orange-colored tonsil

pg 1400

32
Q

Norum disease

A
  • defect of the LCAT protein
  • total loss: familial LCAT deficiency
  • partial loss: fish-eye diseae
  • autosomal recessive, very rare
  • inability of HDl to take cholesterol from cells due to loss of esterification capability
  • symptoms: decreased levels of plasma cholesterol esters and lysolecithin; abnormal LDL (Lp-X) and VLDL; diffuse corneal opacities, swelling of optic nerve, xanthelasmas, targt cell hemolytic anemia, and proteinuria with renal failure

pg 1400

Scientific Foundations (46 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions