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Digestive Systems, Nutrition, and Metabolism > Lipoproteins > Flashcards

Lipoproteins Flashcards

1
Q

Job of cholesterol and phospholipid concentrations

A

Too much cholesterol: phospholipid game too strong. too solid. Not enough, phospholipid concentration too loose. weak guard.

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2
Q

Besides cell membranes, what is cholesterol’s job?

A
  1. steroid hormone synth (dr. z)
  2. bile acids
  3. vitamin D synth
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3
Q

List the ways liver maintains cholesterol in the body

A
  1. Cholesterol synth (the bulk of the cholesterol pools)
  2. Diet (minor poriton)
  3. Extrahepatic tissues via HDL and LDL
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4
Q

List steps in cholesterol synth. Note that you are responsible for step 3 at the very least. Describe the rate limiting . Where does step 3 occur?

A
  1. 2 acetyl CoA (2C) converted to acetoacetyl CoA (4C) using Thiolase. CoA released
  2. acetoacetyl CoA (4C) + another acetyl CoA converted to 3-hydroxy-3-methylglutary CoA (6C…known as HMG CoA) using HMG CoA synthase. Coa released
  3. (YOU MUST KNOW THIS) HMG CoA converted to Mevalonic Acid using 2 NADPH and HMG CoA reductase. This is the rate-limiting step. CoA released. Step 3 occurs in cytosol (the enzyme HMG CoA reductase is in the SER membrane)
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5
Q

What enzyme do statins target to lower cholesterol?

A

HMG CoA reductase. note that by targeting this, statins also wreck dolichol + ubiquinone (coenzyme Q) (both these guys come from isopentyl pyrophosphate), and farnesyl pyrophosphate

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6
Q

What is required to get from mevalonic acid (C6) to cholesterol (C27)?

A
  1. 14 NADPH, fosters the reducing power for 1 cholesterol

2. 18 ATP for 1 cholesterol

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7
Q

What is IPP? What is it a precursor for?

A

IPP = isopentyl pyrophosphate (5C). Precursor for

  1. Dolichol -> used in glycoprotein synth
  2. Ubiquinone (aka coenzyme Q, which is used for electron transport)
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8
Q

What is FPP? What is it a precursor for?

A

FPP - Farnesyl pyrophosphate (15C). Farnesylation of lipid anchored proteins such as ras, lamin (nuclear protein)

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9
Q

When does cholesterol synth occur? why?

A

Energy consumption (14 NADPH and 18 ATP) leads cholesterol synth to only occur in:
1. fed state
2. have a lot of energy to begin with
Will not happen if starving for ATP.

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10
Q

What is SREBP2 and SCAP? What is the job of SCAP? What is Insig? What is COP-II

A

Sterol response element binding protein (a transcription factor). Embedded in the ER and bound to SCAP protein (SREBP2 Cleavage Activating Protein). SCAP has a sensing domain, sensing how much cholesterol is in the membrane. in cases of high cholesterol, it bind to Insig protein. The Insig-SCAP-SREBP2 complex is then rapidly degraded through ubiquitination and proteasome. COP-II is the protein SCAP binds to in cases of low cholesterol.

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11
Q

What happens in cases of lower cholesterol?

A

When Cholesterol levels are low, SCAP binds to COP-II instead of Insig. Remember that COP-II is for intracellular trafficking. This COP-II-SCAP-SREBP2 complex is then sent to the golgi. Protease 1 and 2 remove the SREBP2 complex from the COP-II-SCAP complex. SREBP2 is now free to enter the nucleus (bind to SRE) and activate HMG CoA Reductase gene, which leads to more HMG CoA reductase to make more mevalanic, increasing production of cholesterol.

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12
Q

What is special about HMG CoA reductase? What happens if there is sufficient cholesterol?

A

It is an ER protein and has a sterol sensing domain. When cholesterol levels are solid, Insig binds to HMG CoA Reductase, targets it to the proteasome, and gets wrecked. otherwise it stays in the ER

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13
Q

How does phosphorylation affect HMG CoA Reductase (HMGR from now on What enzymes are responsible for adding and removing the phophates?

A

Phosphorylaiton: HMGR is inactive
Dephosphoryaltion: HMGR is on.
AMPK (K = kinase = adds phosphates) = phosphorylates
HMGR phosphatase takes off the phosphate.

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14
Q

What is AMPK? How does this relate to HMGR regulation?

A

AMPK = AMP Kinase, which is activated in the presence of AMP. ATP is measurment of energy levels in the cell. AMP is the weakest form. If there is a lot of AMP, there is a lack of energy, causing AMPK to deactivate HMGR with a phosphorylation. AMP = allosteric regulator of AMPK

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15
Q

How does insulin affect cholesterol regulation?

A

Insulin is released when we eat, hance correlating directly with high energy levels. So, it should make sense that insulin stimulates HMGR activity by promoting dephosphorylation (through HMGR phosphatase)

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16
Q

How does glucagon affect cholesterol regulation?

A

Glucagon is released when we have not eaten. That means, it is released when our energy states are lower. As a result, it should make sense that, like AMPK itself, it too promotes phosphorylation of HMGR in order to turn it off and save energy.

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17
Q

How do statins regulate cholesterol synth?

A

They are structural analogs of substrate HMG CoA. They specifically competitively inhibit (being binding to HMGR) cholesterol synth.

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18
Q

Mice were genetically engineered to express HMG CoA reductase in which Serine 871 (a phosphorylation site) was replaced by alanine. Which one of the following statements about the mutated enzyme is most likely correct:
A.The enzyme is nonresponsive to statins
B.The enzyme is nonresponsive to the SREBP-SCAP regulatory system
C.The enzyme is nonresponsive to ATP depletion
D.The enzyme is unable to be degraded by the ubiquitin-proteasome system.

A

C.The enzyme is nonresponsive to ATP depletion

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19
Q

What is the purpose of lipoproteins?

A

Lipoproteins (VLDL, LDL, HDL) are proteins that transport esterifeid cholesterols (og form) since these cholesterols are too hydrophobic to dissolve in blood.

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20
Q

Describe lipoproteins

A

Has polar surface, monolayer made of phospholipids or cholesterol. Has apoproteins imbedded in them. the core of the lipoprotein is hydrophobic…usually mad of TAGs or the cholesterol esters.

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21
Q

How do you classify lipoproteins?

A
  1. Based on size

2. Based on what they hold

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22
Q

What is HDL? LDL? VLDL? Chylomicron? Which ones are mainly composed of lipids? Correlation between liprotein density and protein content? Which one has the shortest halflife?

A

High desnsity lipoprotein, lo desnisity, very low density lipoprotein. Chylomicron is a very giant lipoprotein. Chylomicrons and VLDLs are mainly composed of lipids. Note that the dense they get, the more protein they have? Shortest halflife = chylomicron

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23
Q

How do you analyze lipoprotein content? Which lipoprotein is likely to be at the top?

A
  1. Ultrafication
  2. Electrophoretic mobility
    Note that the least dense (VLDL) lipoproteins will be found at the top
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24
Q

Which lipoproteins are mainly made of TAGs? Have the least amount of TAGs? The most cholesterol?

A
  1. Chylomicrons annd VLDL
  2. HDL and LDL
  3. Note that because HDL and LDL have the high densities, they have the most cholesterol, but LDL carries more cholesterol than HDL
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25
Q

What are apolipoproteins? What do they do?

A

These are proteins without the lipid (apo-). These guys:

  1. Act as structural components
  2. Maintain lipid components in solution (major key)
  3. Act as recognition sites or ligands for receptors
  4. Act as activators or coenzymes (activators of enzymes) for enzymes involved in lipid metabolism
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26
Q

Where do you get chylomicrons? How are they packaged? What do they carry, specifically?

A

Found in the intestine enterocytes. They are dietary lipids that we absorb. They are packaged by ApoB48. Chylomicrons carry TAGs. They also carry cholesterol and cholesteryl esters, but 90% of their cargo are TAGs. Know this.

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27
Q

How do enterocytes absorb cholesterol?

A

NPC1L1, receptor on enterocytes, is responsible for taking up plant sterols (and cholesterol). Since plant sterols are not good for us, they are sent back into intestine transporter called ABCG5/8. The cholesterol, however, is esterified (ditches the OH that was attached initially) and is packaged into chylomicrons.

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28
Q

What is MTTP?

A

MTTP (microsomal triglyceride transfer protein) is a chaperone protein which helps package the chylomicrons.

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29
Q

What was the logic in using plant sterols to lower cholesterol?

A

Since NPC1L1 absorbs both cholesterol and plant sterols, the idea was to consume more plant sterols so that there was no opportunity to intake as much cholesterol, leading to lowered cholesterol levels. This only worked marginally.

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30
Q

Ezetimide

A

Inhibitor of NPC1L1 transporter. This eradicated both cholesterol and plant sterol absorption Used in conjunction with statins.

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31
Q

What is sitosterolemia (Phytosteryolemia)? How do you treat this?

A

Disease in which mutation of ABCG5/8 causes an accumulation of plant sterols in the body (they end up being stuck in the enterocytes). Treat with Ezetimibe, which blocks NPC1L1 channel so that neither cholesterol nor plant sterols can enter the enterocyte.

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32
Q

What is the job of MTTP and apoB48?

A

apoB48 transports TAGs to the chylopmicrons and stickes with it. MTTP is the cotransporters that allows this to happen.

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33
Q

How do chylomicrons enter our circulation?

A

Through lymphatic system, leaving through thoracic duct, which empties into subclavian vein.

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34
Q

How are chylomicrons metabolized once apoB48 enters the lymphatic system? What is special about CII?

A

After entering the lympatic system, it enters the circulation while in the circulation, the apoB48-chylomicron complex interact with apoE and apoCII. apoE and apoCII are bound to HDL. HDL releases them and binds them the the chylomicron, which still has apoB48. CII specifically activated Lipoprotein lipase (LPL). Upon getting CII, it take the TAGs stored int he chylomicrons. The apoB48-E-CII-chylomicron complex is now refered to as a remenant. The remenant returns the CII to LDL annd the rest of the remenant is picked up by the liver (apoE is the guy in charge here). they are then degraded.

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35
Q

What is lipoprotein lipase (LPL)?

A

Extracellular enzyme that lines our capillaries near peripheral tissue. Activated by CII.

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36
Q

What tissues have LPL?

A

adipose, cardiac, muscle tissues.

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37
Q

How does insuline affect lpl expression?

A

As insulin levels go up, LPL expression in adipose tissue is stimulated. Remember that insulin is released every time you eat.

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38
Q

What is exogenous method of obtaining cholesterol?

A

means to get cholesterol from diet using the chylomicrons. they are cleared from blood within a few hours, even though a specific molecule takes minutes to be cleared from the blood. Aftering fo ra night should wipe out all the chylomicrons from the bloodstream.

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39
Q

How does chylomicron look like in plasma?

A

milky appearance

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40
Q

What happens when you remove the TAGs in the chylomicrons?

A

The concentration of cholesterol in the chylomicrons go up. Remember, it carries both. Increaed levels of remnant chyromicrons = increased amount of cholesterol in the body, which contributes to atherosclerosis.

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41
Q

What is the endogenous pathway of cholesterol delivery?

A

Means to transfer synthesized cholesterols from liver to the rest of the body. Involves using VLDLs (come from the liver), which are converted to intermediate density lipoproteins (IDL), which are converted to low density lipoproteins.

42
Q

Explain the VLDL metabolism

A

VLDL from the liver (which carries synthed cholesterol and TAGs) is bound to apoB100. They are released directly into circulation (no need for lymphatic pathway because its not as big as chylomicrons). The VLDL-apoB100 complex picks up apoE and apoCLL from HDL.. Full complex goes to peripheral tissue and bindss to LPL via CII. The peripheral tissue takes up the TAGs. The now smaller VLDL is call an IDL, still bound to apoB100 and apoE, and having given apoCII up back to HDL. Now, both VLDL and IDL interact with HDL to GAIN cholesterol. IDL with the apoB100 and apoE complex gets taken up by the liver, thanks to apoB100. Alternatively, the apoE could be remodeled, converting IDL to LDL before binding back to HDL. This LDL is rich in cholesterol. LDL can either go back tot he liver or deliver cholesterol to extrahepatic tissues.

43
Q

Which apo binds to LDL receptor?

A

apoB100

44
Q

what does LDL-apoB100 complex do?

A

travels to periphery (extrahepatic tissue) to deliver cholesterol. The rest of the cholesterol is returned to the liver.

45
Q

LDL, IDL, VLDL. pick the one with highest density

A

LDL

46
Q

VLDL + apo’s E, CII, and B100

A

Synthesized in liver Transport endogenous TAG Half-life of a VLDL particle is expressed in terms of hours

47
Q

IDL + apo’s E, and B100

A

IDL synthesized from VLDL during VLDL degradation Can be cleared by liver through B100-LDL receptor interaction Precursor to LDL

48
Q

LDL and B100

A

Synthesized from IDL Hepatic lipase hydrolyzes excess TAGS and phospholipids The half-life of LDL particles is long, on the order of days. LDL particle contain the majority of blood-borne cholesterol (in a fasting blood sample).

49
Q

Difference between chylomicrons and LDLs.

A

Chylomicrons were obtained through diet. LDLs were made int he liver.

50
Q

What is VLDL?

A
  1. made by liver
  2. rich in TAGs
  3. requires MTTP (just like chylomicrons) in order to be assembled in hepatocytes
  4. They serve similar role to chylomicrons, but they transport lipids FROM liver to extrahepatic tissue instead of doing so through our diet.
  5. Relies on apoB100
  6. aquires apoE and apoCII, just like chylomicrons
  7. smaller than chylomicrons, but size is also dependent on amount of TAGs it is holding.
51
Q

why can’t apoB48 bind to LDL receptor but apoB100 can?

A

because apoB48 is 48% smaller than apoB100.

52
Q

What is job of MTTP? What happens if you screw this up?

A

chaperone protein. helps load the TAGs onto chylomicrons and VLDLs. IF MTTP takes L, you cannot load cholesterol into VLDL or chylomicrons. You essentially cannot assemble either VLDL or chylomicrons. For chylomicrons, it means oyu would not be able to assemble or absorb DIETARY lipids. Since VLDL take the L too, you cannot send out TAGs or cholesterol to the peripheral tissue.

53
Q

Abetalipoproteinemia (ABL)….and what disease are they less likely to develop?

A

Mutation of MTTP. Can’t make chylomicrons and cannot absorb their fats (hypocholesterloemia). Patients present with steatorrhea (fatty feces). Also have deficiencies in fat-soluble vitamins (ADEK). Since VLDL is not being sent from the liver (not being assembled to be sent to the extrahepatic organs), the liver gets fatty too. Oddly enough, patients are less likely to develop cardiovascular disease since they have less circulating fat and cholesterol.

54
Q

Familial hypobetalipoproteinemia (FHBL)

A

Autosomal codominant disease that’s similar to abetalipoproteinemia.=, except they have apoB gene mutation, leading to truncated apoB. Not as severe. Endogenous pathway is ok, but exogenous pathway suffers.Essentially, the issue revolves around a decrease in LDLR, decrease in apoB100, or increase in PCSK9

55
Q

What are IDLs (VLDL remenants)?

A
  1. ENRICHED in cholesterol thanks to HDL.
  2. contains apoE and apoB100
  3. Can be cleared by apoB100-LDL receptor interaction (apoB100 can touch the LDL receptor.)
  4. Fosters removal of TAGs from VLDL by peripheral tissue
56
Q

What is LDL? What correlation exists with the presence of LDL?

A

Holds the bad cholesterol. Mos to the cholesterol in our circulation is associated with LDL. LDL is still aimed to delivering the cholesterol to extrahepatic tissue. LDL can return to liver by binding to LDL receptor, with the excess cholesterol. Thank the apoB100. There is a super strong correlation between the presence of LDL and atherosclerosic cardiovascular events.

57
Q

Explain the point of the LDL receptor What happens to LDL when it binds to LDL receptor? What are the 3 things SREBP2 regulates?

A

Expressed on hepatocytes, bind apoB100, attached to LDL. Upon binding, LDL and receptor is endocytoced and the receptor is sent back to surface. The cholesterol is now int he cells. High levels of cholesterol shuts down HMG CoA reductase expression. Think back to SREBP2. So technically, SREBP2 also controls LDL receptor presence, in addition to the production of cholesterolSREBP2 also enhances ACAT (acyl CoA: cholesterol acyl tranferase) activity

58
Q

What happens if you have too much cholesterol?

A

SREBP2 will not go to the nucleus and will not activate LDL receptor gene via SRE binding, and LDL will not be binding to the hepatocytes.

59
Q 
Failure to bind LDL to its receptor results in uncontrolled synthesis of cholesterol. This occurs because synthesis of which of the following enzymes is not repressed?
A.ACAT
B.HMG-CoA reductase
C.LCAT
D.Lipoprotein lipase
A

HMGR

60
Q

What do statins do?

A

Inhibits HMGR specifically. This leads to low levels of cholesterol int he cell.

61
Q

The HMG CoA reductase inhibitors (also known as the “statins”) cause all of the following EXCEPT which ONE?
A.Decreased de novo cholesterol synthesis
B.Decreased synthesis of HMG CoA reductase
C.Decreased intracellular supply of cholesterol
D.Increased number of specific cell-surface LDL receptors on hepatocyte cell membranes
E.Increased binding and uptake of circulating LDLs into hepatocytes.

A

B.Decreased synthesis of HMG CoA reductase. You over looked this the first time you tried this question. The presence of the HMGR inhibitor lower the presence of cholesterol in the cell. SO, SREBP2 will notice this, bind to COPII, and increases HMGR production.

62
Q

What is the correlation between LDL receptors and cardiovasccular disease? Do IDL’s bind to LDL receptors? What about the precursors to LDL and the blockage of the LDL receptor?

A

An increase in the presence of LDL receptors correlates to an increase in the chances of developing cardiovascular disease. Note: IDL’s also bind to LDL receptor since they have apoB100. Also note that the blockage of the LDL receptor would increase the presence of LDL and its corresponding precursors, with the intention of replenishing the prevalance of LDL.

63
Q

What is PCSK9? What is its job?

A

Extracellular protease made in the liver. It targets the LDL receptor and brings the LDL with the LDL receptor to the lysozome to be destroyed instead of allowing the LDL receptor to be brought back to the hepatocyte resurface. In other words, an increase in the amount of PCSK9 decreases the prevalence of LDL receptors and LDL.

64
Q

List the 3 ways LDL receptor levels could be low

A
  1. Defect in LDL receptor synth or mutation sin LDLR, both preventing its proper interaction with LDL
  2. Defect in apoB100 that reduces its interaction with LDL receptor
  3. Increased activity of PCSK9
65
Q

What happens if you prescribe a drug that inhibits PCSK9? Name the drug

A

LDLR is allowed to return to hepatocyte surface, allowing for proper mediation of LDL in circulation. Drug: Repatha

66
Q

Tell me how LDL affects atherosclerosis

A
  1. LDL is circulating in plasma. Unaffected by oxidation factors in the blood, so they stay intact.
  2. When LDL is done circulating in plasma, they return to liver
  3. LDL can penetrate epithelial walls, like in arteries, especially when blood’s under higher pressures and at points of endothelial injury
  4. In the capillary wall, the antioxidants (like vitamin E) normally found in blood are not present, and the LDL gets oxidized.
  5. Ox-LDL is initiating factor for atherosclerotic plaque, as they send signals to immune cells, which now also penetrate into the weakened epithelium
  6. The immune cells (macrophages with Scavenger Receptor A) phagocytose the ox-LDL particles and form foam cells (macrophages filled with lipids). These guys accumulate and create fatty streak, forming plaque.
67
Q

What is the difference between sclerotic plaque and cap on the sclerotic fibrous cap?

A

When the smooth muscle cap on the sclerotic cap is dislodged, it impedes bloodflow and leads to death of neighboring tissue.

68
Q

What are the 2 kinds of molecules derived from LDL ? Which is more dangerous and why?

A

small dense LDL (more dangerous in terms of leading to atherosclerosis) and large buoyant LDL sdLDL are more dangerous since they can get into the epitherlium much easier, increased subendothelial penetration, increased subepithelial binding, increased propensity for being oxidized, and they have a reduced LDL receptor binding, so they are less likely to be cleared by PCSK9.

69
Q

what is Lp(a)? how does it relate to heart disease?

A

Protein surrounding LDL. attached to the surface of LDL. Has homology to the proteins that form clots Lp(a) likely accelerates clot formation. Increase in LP(a) is with heart disease.

70
Q

In 2005, Cohen et al. identified the nonsense mutation C676X in PCSK9 in the Dallas Heart Study population. The mutant PCSK9 protein exhibits lower activity as compared to the wildtype protein (i.e. loss-of-function mutation). Would you expect this mutation to be associated with:
A.Increased LDL-C
B.Decreased LDL-C
C.No impact on LDL-C

A

B.Decreased LDL-C
You may have been overthinking this again. if you decreased the think killing the LDL receptors, you would have more receptors present. an increase in receptors will decrease the amount of LDL-C, where C = cholesterol. Side note, those with this mutation have lower risk of heart disease.

71
Q

Describe HDL’s make-up. Where is it made? What does it do when it enters circulation? What does LCAT do, and what activates it?

A
  1. apo A protein synthesized in the liver and intestine (and secreted into circulation)
  2. Made mainly of apo AI (activator LCAT) and apo AII (activator hepatic lipase). remaining parts are phospholipids. This group is called nascent HDL.
  3. When it hits circulation, it picks up free, used cholesterol in circulation with ABCA1 membrane transporter (which is why it is the good cholesterol) and LCAT (activated by apo A1) converts the free cholesterol to cholesterol esters, changing name to HDL3
  4. HDL2 is the final stage, after it accumulates enough cholesterol esters.
72
Q

What protein does HDL2 use to tranfer cholesterol and to IDL/LDL and TAGs back to HDL2?

A

CETP. note that it is also involved in remodeling IDL to LDL.

73
Q

What happens after HDL2 Cholesterol esters and TAGs are gathered?

A

Drops contents off at liver using hepatic lipase (takes the TAGs) and SRB1 (scavenger receptor on hepatocytes, which prefers to take cholesterol off HDL2). upon removal of cholesterol and TAGs, and becomes HDL3 again.

74
Q

List functions of HDL

A
  1. reservoir of apo CII and apoE for chylomicrons and VLDL/IDL
75
Q

What is LCAT? What happens if it is not available?

A

Lecithin-cholesterol acyltransferase. Literally links lecithin with cholesterol to make cholesterol ester. If into present, the cholesterol cannot be esterified, and thus cannot go into the HDL core. It would just stay on HDL surface, limiting the amount of cholesterol HDL can pick up.

76
Q

What is CETP? What happens if it is not available?

A

Cholesterol ester transfer protein. sends cholesterol esters from HDL to VLDL/IDL, and takes TAGs from VLDL/IDL into HDL. Need to remember transfer directions.

77
Q

What is reverse cholesterol transport? What enzyme is involved in this transfer?

A

Concept of HDL picking up cholesterol from peripheral tissues and bringing them back to liver. ABCA1 protein sends cholesterol from the peripheral proteins into nascent HDL (HDL1). Note that HDL still uses LCAT to convert aquired cholesterol to cholesterol esters to achieve final form (HDL2), which then drops cholesterol and TAGs to liver via hepatic lipase and SRB1. Excess cholesterol becomes bile in liver.

78
Q

T/F HDL can transfer cholesterol to steroid-producing cells.

A

True. Relevant for the testes.

79
Q

How does HDL transfer cholesterol from foam cells/macrophages?

A

Foam cells express ABCA1, which is the key receptor needed to transfer cholesterol from peripheral tissues to nascent and mature HDL cells. The cholesterol is still then sent liver via SRB1 receptor.

80
Q

foam cell

A

macrophage with oxidized LDL inside them

81
Q

equation for total cholesterol

A

Total cholesterol = LDL cholesterol + HDL cholesterol + VLDL cholesterol

82
Q

equation for LDL cholesterol

A

LDL cholesterol= Total cholesterol – HDL cholesterol – VLDL cholesterol

83
Q

Equation for VLDL cholesterol

A

VLDL cholesterol = Triglycerides / 5

84
Q

Friedewald equation?

When does this equation hold true?

A

Friedewald equation:
LDL cholesterol = Total cholesterol – HDL cholesterol – (Total triglycerides/5). Only holds true after fasting, since you need to ditch the chylomicrons in circulation. Also assumes that VLDL’s are at a 5:1 normal ratio. It also assumes that majority of cholesterol is transported by LDL, HDL, and VLDL in fasting plasma.

85
Q 
Reference standards for:
Total cholesterol: 200
LDL-C:
TAGs:
HDL-C:
A

LDL-C: below 100
TAGs: below 150
HDL-C: above 40

86
Q

A 62-year old woman presents for an annual physical examination. She has fasted for 12 hours and a blood sample is drawn for measurement of plasma lipid levels. The clinical chemistry laboratory reports the following: Total cholesterol: 275 mg/ dL Triacylglycerides: 300 mg/dL HDL cholesterol: 40 mg/dL In accord with standard procedure, the laboratory calculates a value for LDL - cholesterol level from these measurements. Into which of the following National Cholesterol Education Program categories does this patient’s LDL - cholesterol level fit?

A 
A.Optimal ( < 100 mg/ dL)
B.Near optimal (100 - 129 mg/dL)
C.Borderline high (130 - 159 mg/dL)
D.High (160 - 189 mg/dL)
E.Very high ( ≥ 190 mg/ dL)
87
Q

Dislipidemia =

A

Imbalamce of TAGs and lipoproteins. Essentially, higher cholesterol levels = bad. Increased of forming plaques.

88
Q

name associated carriers screw up associated with
hypercholesterolemia:
hypertriglyceridemia:
hypoaplphalipoproteinemia:

A

hypercholesterolemia: LDL
hypertriglyceridemia: chylomicrons and VLDL
hyperaplphalipoproteinemia: HDL

89
Q

Difference between primary and secondary dislipidemia

A

Primary: mutation in genes involved in lipid metabolis,
secondary: metabolic disorder like DM, obesity, hypothyroidism, primary bile cirrhosis

90
Q

familial hyperchylomicronemia, type I hyperdislipidemia

A

lipoprotein lipase deficiency or CII (activator of LPL) deficiency. Fasting TAGs is above 1000mg/dl. presents with seveer hyperTAGemia. Will also see milky fasting plasma upon testing, even after overnight fast. Can find recurrent pancreantitis due to chylomicrons getting stuck in the ducts of the capillary and eruptive cutaneous xanthomas on skin after fatty meal.

91
Q

familial hypercholesterolemia: type IIa hyperlipidemia aka hyperbetalipoproteinemia

A

impacts LDL and LDL receptor impacts. Could be PCSK9 is upregulated or LDL receptor issue. note that you would see NORMAL LDL and ELEVATED VLDL. paitents may present with ischemic heart disease. Patients have tendon xanthomas or xanthelasma if present around the eyes. can even ave corneal arcus if lipids deposit in cornea of eye.

92
Q

familial dysbetalipoproteinemia : Type III hyperlipidemia

A

Caused by apoE deficiency. expect accumulation in IDL. Increases in choleterol and TAGs. New equation:
Total cholesterol = LDL-C + HDL-C + VLDL-C
+ IDL-C. Patients present with palmar crease xanthomas (yellow in palm creases…KEY feature). increased risk of heart disease

93
Q

What’s special about apoE2?

A

Binds poorly to its receptor. likely found in people with Type III dislipedemia.

94
Q

apo A1 deficiency

A

AI is required for LCAT, used by nascent HDL. WIthout it, you won’t get HDL, and no HDL gathering. Expect cholesrterol deposits in the eye. low hdl levels.

95
Q

LCAT deficiency

A

even more severe eye issue than apoA1 deficiency. no cholesterol is able to be broguht back to liver. low hdl levels…nascent HDL never matures.

96
Q

tangier disease-absence of ABCA1

A

ABCA1 is on peripheral tissue, and tranfers cholesterol to nacscent HDL . so, impaired HDL maturation. decreased HDL, yellow discoloration of tonsils. higher risk of heart disease.

97
Q

A young girl with a history of severe abdominal pain was taken to her local hospital at 5 a.m. in severe distress. Blood was drawn, and the plasma appeared milky, with the triacylglycerol level in excess of 1,000 mg/dl (normal = 4–150 mg/dl). The patient was placed on a diet severely limited in fat, but supplemented with medium-chain fatty acids. Which of the following lipoprotein particles are most likely responsible for the appearance of the patient’s plasma?
A. Chylomicrons. B. Very-low-density lipoproteins. C. Intermediate-density lipoproteins. D. Low-density-lipoproteins. E. High-density-lipoproteins.

A

A. Chylomicrons

98
Q

Medium-chain fatty acids are given because they:
A.form smaller chylomicrons than long-chain fatty acids.
B.enter directly into the portal blood, and can be metabolized by the liver.
C.are activators of lipoprotein lipase
D.stimulates VLDL production by the liver.

A

B.enter directly into the portal blood, and can be metabolized by the liver.

99
Q 
Which one of the following proteins is most likely to be deficient in chylomicron patient?
A.Apo B100
B.Apo B48
C.Apo CII
D.MTTP
E.CETP
A

C.Apo CII

100
Q

Job of bile acid sequestrant and soluble fiber

A

binds to bile and lower cholesterol amounts in hepatocytes. but this also increases LDL receptor expression!!!!!! this leads to decrease in LDL in circulation.

101
Q

Niacin

A

Vitamin B3 or Nicotinic Acid and
•Niacin’s beneficial effect on cholesterol levels were first reported in 1955 became the first treatment for high cholesterol
In adipose tissue: decrease free fatty acid release
In liver: inhibit diacylglycerol acyltranferase-2, a key enzyme for TG synthesis
In plasma: increases LPL activity and HDL half-life
•Niacin is considered one of the most effective drug for increasing HDL-C

102
Q

Fibrates

A

Fibrates:
•Target the transcription factor PPAR- which stimulates the transcription of a number of genes that facilitate lipid metabolism, including LPL and apo A-1
•Fibrates are agents used mainly in patients with hypertriglyceridemia - not as useful for treating increased cholesterol
•Gemfibrozil is an example
Niacin and Fibrates

Digestive Systems, Nutrition, and Metabolism (20 decks)

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