Chapter 15: Lipid Synthesis and Storage (2)

Question 1

What is the purpose of apoA-1?

Answer 1

used for cholesterol recovery from fatty streaks in the BV.

Docks LCAT

Question 2

What does LCAT stand for?

Answer 2

lecithin-cholesterol acyltransferase

Question 3

What is another name for LCAT?

Answer 3

PCAT phophatyidyl choline-cholesterol acyltransferase

Question 4

What is the function of LCAT?

Answer 4

adds a fatty acid to cholesterol, producing cholesterol esters which dissolve in the core of the HDL

Question 5

What is purpose of CETP?

Answer 5

The cholesterol esters picked up in the periphery by HDL can be distributed to other lipoprotein particles such as VLDL remnants (IDL), converting them to LDL

Question 6

What does CETP stand for?

Answer 6

cholesterol ester transfer protein

Question 7

HDL cholesterol picked up in the periphery can enter cells through what receptor?

Answer 7

SR-B1 scavenger receptor B1

Question 8

SR-B1 is expressed in high levels in what tissues?

Answer 8

in hepatocytes and steroidogenic tissues, including ovaries, testes, and areas of the adrenals

Question 9

Does SR-B1 mediate endocytosis of HDL?

Answer 9

no but rather transfers cholesterol into the cell by a mechanism not clearly known

Question 10

Damage to the endothelium of BV may be related to what factors?

Answer 10

• normal turbulence of the blood
• elevated LDL
• oxidized LDL
• free radicals from cigarette smoking
• homocystinemia

Question 11

Describe how atherosclerotic plaques form.

Answer 11

1. endothelial dyfunction causes procoagulation of cells around damaged endothelium.
2. Local inflammation recruit monocytes and macrophages with subsequent production of ROS. LDL can become oxidized then taken up, macrophages become laden with cholesterol (foam cells)
3. subendothelial accumulation of cholesterol-laden macrophages producing fatty streaks
4. as fatty streaks enlarge, necrotic tissue and free lipid accumulates surrounded by epitheloid cells and eventually smooth muscle cells and an advanced plaque with a fibrous cap.
5. Plaque eventually begins to occlude the blood vessel and could break off leading to thrombosis

Question 12

How is HDL protective in cholesterol accumulation?

Answer 12

1. HDL is protective by picking up accumulating cholesterol before the advanced lesion forms. ApoA-1 activates LCAT which in turn adds a fatty acid to cholesterol to produce a cholesterol ester that dissolves in the core of HDL
2. HDL can be subsequently picked up by liver through the apoE receptor or delivered cholesterol through the scavenger receptor.
3. The HDL may also transfer the cholesterol to an IDL, reforming a normal unoxidized LDL particle

Question 13

How does vitamin E prevent endothelial damage?

Answer 13

protects LDL from oxidation and may prevent peroxidation of membrane lipids

Question 14

List all the dyslipidemias and their names.

Answer 14

• Type I: Familial Dyslipidemia (Hypertriglyceridemia) (Hyperchylomicronemia)
• Type IIa: Familial Dyslipidemia (Familial Hypercholesterolemia)
• Type III: Familial Dyslipidemia (Dysbetalipoproteinemia)
• Type IV: Familial Dyslipidemia (Hypertriglyceridemia)
• Type V: Hyperlipideia secondary to Diabetes
• Abetalipoproteinemia (Hypobetalipoproteinemia) - a hypolipidemia

Question 15

What is the deficiency in primary Type I hyperlipidemia?

Answer 15

• familial lipoprotein lipase (rare) deficiency
• apoC-II (rare) deficiency

Question 16

Inheritance of primary Type I hyperlipidemia?

Answer 16

AR

Question 17

Lipid elevated in blood in primary Type I hyperlipidemia?

Answer 17

triglycerides

Question 18

Which lipoprotein is elevated in those with primary Type I hyperlipidemia?

Answer 18

chylomicrons

Question 19

What are some symptoms of primary Type I hyperlipidemia?

Answer 19

red-orange eruptive xanthomas
fatty liver
acute pancreatitis
abdominal pain after fatty meal

Question 20

What is the deficiency causing primary type IIa hyperlipidemia?

Answer 20

LDL receptor deficiency

Question 21

What is the inheritance pattern of primary Type IIa hyperlipidemia?

Answer 21

AD

Question 22

What is the lipid elevated in the blood of an individual with primary Type IIa hyperlipidemia?

Answer 22

cholesterol

Question 23

What is the lipoprotein elevated in the blood in a person with primary Type IIa hyperlipidemia?

Answer 23

LDL

Question 24

What are the symptoms in those with primary type IIa hyperlipidemia?

Answer 24

high risk of atherosclerosis and coronary artery disease

xanthomas of achilles tendon

tuberous xanthomas on elbows

xanthelasmas

corneal arcus

• If patient homozygous, usually death < 20 years

Question 25

What are factors that exacerbate the symptoms associated with that Type I hypertriglyceridemia?

Answer 25

• decreased glucose and triglyceride uptake in adipose tissue
• overactive hormone-sensitive lipase
• unreactive lipoprotein lipase

Question 26

What is the most common type of hyperlipidemia?

Answer 26

Type V

Question 27

Why do individuals with hyperlipidemia Type V have elevated serum triclycerides in VLDL and chylomicrons in response to a meal containing carbs and fat respectively?

Answer 27

insulin has important regulatory function in adipose tissue and promotes LPL activity by increasing transcription of its gene.

therefore in diabetes there is low activity of LPL and the inability. to degrade the serum triglycerides in lipoproteins to facilitate uptake of fatty acids into adipocytes

Question 28

Abetalipoproteinemia is a hyper or hypolipidemia?

Answer 28

hypolipidemia

Question 29

What is the pathology behind abetalipoproteinemia?

Answer 29

patients have low to absent serum apoB-100 and apoB-48.

because chylomicron levels are low, fat accumulates in intestinal enterocytes and in hepatocytes.

Essential fatty acids and vitamins A and E are not well absorbed.

Question 30

What are some symptoms of abetalipoproteinemia?

Answer 30

• steatorrhea
• cerebellar ataxia
• pigmentary degeneration in the retina
• acanthocytes (thorny appearing erythrocytes)
• possible loss of night vision

Question 31

Cholesterol is req’d for what biosynthetic proceses?

Answer 31

membrane synthesis, steroid and vitamin D synthesis, and in the liver, bile acid synthesis

Question 32

Cholestyramine MOA.

Answer 32

increase elimination of bile salts and force the liver to increase their synthesis from cholesterol, thus lowering the internal level of cholesterol in the hepatocytes

inc. LDL receptor expression,

Question 33

MOA of HMG-CoA reductase inhibitors?

Answer 33

inhibit de novo cholesterol synthesis in the hepatocyte, which subsequently increases LDL receptor expression

Question 34

What is the importance of farnesyl PPi?

Answer 34

• synthesis of CoQ ETC
• synthesis of dolichol PPi for N-linked glycosylation of proteins
• prenylation of proteins (a posttranslational modification) that needs to be held in the cell membrane by a lipid tail.

Question 35

Insulin activates HMG CoA reductase through phosphorylation or dephorylation?

Answer 35

dephosphrylation

Question 36

How does glucagon affect HMG CoA reductase?

Answer 36

inhibits it

Question 37

What should be the ideal blood level of LDL?

Answer 37

< 100 mg/dL

Question 38

What is the max time for statins to reach their full effect?

Answer 38

4-6 weeks

Question 39

When should LFTs be measured after taking statins?

Answer 39

within 2-3 months

Question 40

Explain the pathology of muscle dysfunction after taking statins.

Answer 40

lessening of downstream synthesis of CoQ req’d in the ETC so less ability to produce ATP that is req’d for muscle contraction

Question 41

Why is there red-brown urine findings after taking statin drugs?

Answer 41

breakdown of myoglobin because of damaged muscle cells

Question 42

Why could there be increase CRP after using statins? What is an associated condition with elevated CRP?

Answer 42

is a liver protein that is secreted inn inflammation. There is direct correlation between elevated CRP and atherosclerosis.

Question 43

Draw out the path in cholesterol metabolism.

Answer 43