Clinical Correlates 5 Cholesterol Flashcards Preview

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Flashcards in Clinical Correlates 5 Cholesterol Deck (17):
1

Statins are medications that function as competitive inhibitors of ___, thus reducing the serum level of cholesterol. Statins have been effective in regulating circulating cholesterol levels in patients with hypercholesterolemia.

HMG-CoA reductase

2

Gallstones can be made of cholesterol. ___ is a medication used to inhibit the formation of cholesterol gallstones. This medication is a hydrophilic bile salt that decreases the content of cholesterol in bile.

Ursodeoxycholate

3

___ is the buildup of lipid-rich plaques in the intima layer of arteries. Blood clots can form on these lipid-rich plaques, or part of the plaque may suddenly break loose, occluding a coronary or cerebral artery. Occlusion of a coronary artery can cause a myocardial infarct (heart attack), and occlusion of a cerebral artery can cause an ischemic cerebrovascular accident (stroke).

Atherosclerosis

4

Bile acid sequestrants, such as cholestyramine, bind with bile acids in the intestinal lumen. The insoluble complex of bile acid sequestrant and bile acid is eliminated in the stool. This causes ___ _____. As the body ___ dietary cholesterol, the cells take up low-density lipoprotein (LDL) from circulation, which results in a ____ of circulating cholesterol.

fecal loss of cholesterol
loses
lowering

5

The agent ____a member of the ___ class of lipid-lowering agents, activates the transcription of lipoprotein lipase by activating the PPAR (peroxisome proliferator-activated receptors) family of receptors. Therefore, the drug ____ the level of VLDLs and other triglyceride-rich lipoproteins.

gemfibrozil,
fibrate
decreases

6

____ is a disease of cholesterol transport. The first case was identified in a patient who lived on the island of Tangier and who had characteristic orange-colored tonsils, a very low HDL level, and an enlarged ___ ___ Because of a mutation in a transport protein, cholesterol cannot properly exit the cell to bind to apo A (forming HDL). This results in a very low HDL level.

Tangier disease
liver and spleen.

7

LCAT deficiency results in an inability to convert cholesterol associated with ____ to cholesterol esters. Ordinarily, these cholesterol esters would be transferred to other ____, which would then be taken up by receptors in the liver. Therefore, by inducing esterification of cholesterol, LCAT is important for the continued removal of cholesterol from the periphery. Clinical manifestations include ____ in the kidneys, red blood cells, and the cornea of the eyes.

HDL
lipoproteins
defects

8

1. Which of the following apoproteins is an activator of lipoprotein lipase?
(A) Apo A
(B) Apo B
(C) Apo C-II
(D) Apo D
(E) Apo E

C. Apo C-II is an activator of lipoprotein lipase, Apo A is the major apolipoprotein of HDL, Apo B100 is the major apolipoprotein of LDL and VLDL (and apo B48 is the major apolipoprotein of chylomicrons), and Apo E is transferred by HDL to nascent chylomicrons and nascent VLDL to form mature forms of those particles. Apo D is unlike all the other apolipoproteins, and its role in metabolism has yet to be clearly defined.

9

2. The major carriers of triacylglycerols are which of the following?
(A) Chylomicrons and VLDL
(B) IDL and LDL
(C) VLDL and LDL
(D) HDL and LDL
(E) Chylomicrons and LDL

A. The major carriers of triacylglycerols are chylomicrons (synthesized in the intestine from dietary fat) and VLDL (synthesized in the liver). The triacylglycerols are digested in capillaries by lipoprotein lipase. The fatty acids that are produced are used for energy by cells or are converted back to triacylglycerols and stored. IDL and LDL are digestion products of VLDL, which have reduced amounts of triglyceride compared with VLDL. HDL has the least amount of triglyceride of any lipoprotein particle.

10

3. A 40-year-old Hispanic woman with a body mass index of 34 presents with acute right upper quadrant pain, nausea, and vomiting after eating a meal rich in lipids. She is diagnosed with having cholelithiasis and is placed on a bile salt analog that is used to inhibit the formation of cholesterol gallstones. Which of the following is an example of a bile salt?
(A) HMG-CoA
(B) Mevalonate
(C) Squalene
(D) Lanosterol
(E) Chenocholic acid

E. Chenocholic acid is an example of a bile salt. HMG-CoA, mevalonate, squalene, and lanosterol are intermediates in cholesterol synthesis. Bile salts are synthesized from cholesterol in the liver, are stored in the gallbladder, and are released to facilitate lipid digestion in the intestines.

11

4. An 8-year-old boy presents with orangecolored tonsils, a very low HDL level, and an enlarged liver and spleen and is diagnosed with Tangier disease. Which of the following statements best describes HDL?
(A) It is produced in skeletal muscle.
(B) It scavenges cholesterol from cell membranes.
(C) Its major protein is apo E.
(D) It is formed when VLDL is digested by lipoprotein lipase.
(E) It activates ACAT.

B. HDL scavenges cholesterol from cell membranes and lipoproteins. HDL is produced in the liver (not muscle), and its major apoprotein is apo A. IDL is formed when VLDL
is digested by lipoprotein lipase. Cholesterol activates ACAT, which converts cholesterol to cholesterol esters for storage in cells.

12

5. A 40-year-old man presents with chest pain that radiates to his left jaw and shoulder. He is diagnosed with a myocardial infarction and is prescribed a statin medication. Statins are competitive inhibitors of HMG-CoA reductase, which converts HMG-CoA to which of the following?
(A) Mevalonate
(B) Isopentenyl pyrophosphate
(C) Geranyl pyrophosphate
(D) Farnesyl pyrophosphate
(E) Cholesterol

A. HMG-CoA reductase converts HMG-CoA to mevalonate, using two NADPH molecules. Isopentenyl pyrophosphate, geranyl pyrophosphate, and farnesyl pyrophosphate are intermediates in cholesterol synthesis. Mevalonate is required to synthesize isopentenyl pyrophosphate, which leads to geranyl and farnesyl pyrophosphate production.

13

6. A 45-year-old woman presents with oily, foul-smelling stool, which appears to be due to an obstruction of the bile duct. Which of the following statements correctly describes bile salts?
(A) They can act as detergents, aiding in lipid
digestion.
(B) They are stored in the intestines.
(C) Ninety-five percent of bile salts are excreted
in the feces, and 5% are recycled back to the liver.
(D) Bile salts are synthesized in the intestines.
(E) Squalene and lanosterol are examples of
bile salts.

A. Bile salts, synthesized in the liver and stored in the gallbladder, act as detergents, aiding in lipid digestion. The bile salts are secreted into the intestine in response to cholecystokinin. An inadequate concentration of bile salts in the intestines can lead to oily, foulsmelling stool with a high fat content, a condition known as steatorrhea. Ninety-five percent of bile salts are recycled back to the liver, and 5% are excreted in the feces. Squalene and lanosterol are intermediary compounds in cholesterol synthesis, not bile acid synthesis.

14

7. A 55-year-old woman presents with crushing substernal chest pain and shortness of breath. A coronary artery is occluded owing to an atherosclerotic
plaque, and a high myocardial infarct is diagnosed. High serum HDL levels are protective against the development of atherosclerosis because HDL does which of the following?
(A) Inhibits cholesterol production by the liver
(B) Inhibits HMG-CoA reductase
(C) Increases VLDL production
(D) Increases LDL production
(E) Brings cholesterol esters back to the liver

E. HDL is known as the ‘‘good’’ lipoprotein particle because HDL scavenges cholesterol from the periphery (from cell membranes and from other lipoproteins) and brings cholesterol esters back to the liver, where they can be converted to and excreted as bile salts. This is known as reverse cholesterol transport. HDL does not inhibit cholesterol production by the liver. Statin medications inhibit HMG-CoA reductase activity, not HDL production. Increasing VLDL or LDL will facilitate the development of atherosclerosis, not protect against its development.

15

8. A 30-year-old man presents with weakness in his right upper and lower extremities. He is diagnosed with an acute middle cerebral artery stroke secondary to atherosclerosis. Genetic studies show that he has familial hypercholesterolemia, type II, a disorder caused by a deficiency of LDL receptors. Which of the following statements best describes patients with type II familial hypercholesterolemia?
(A) After LDL binds to the LDL receptor, the LDL is degraded extracellularly.
(B) The number of LDL receptors on the surface of hepatocytes increases.
(C) Cholesterol synthesis by hepatocytes increases.
(D) Excessive cholesterol is released by LDL.
(E) The cholesterol level in the serum decreases.

C. Familial hypercholesterolemia, type II, is due to a mutation in the LDL receptor, which, in a variety of mechanisms, prevents endocytosis of the receptor with bound LDL. Cholesterol synthesis by hepatocytes increases in patients with this disorder because HMG-CoA reductase is not properly inhibited. Normally, after LDL binds to the LDL receptor, the receptor–LDL complex is internalized, the LDL is degraded intracellularly, and the cholesterol released from the LDL migrates to the cytosol. The increase in intracellular cholesterol inhibits HMG-CoA reductase, resulting in decreased cholesterol synthesis by hepatocytes. Because the LDL receptor is deficient in patients with this disease, LDL cannot be taken up by hepatocytes (to release cholesterol), and an extremely high serum cholesterol level results, both from increased cellular synthesis and release of VLDL, and high levels of LDL particles in the circulation.

16

9. A 40-year-old woman presents with an LDL serum level of 400 (recommended level is

A. Normally, LDL, after binding to its receptor and internalization into the cell, is digested by lysosomal enzymes to release cholesterol. High levels of intracellular cholesterol inhibit HMG-CoA reductase, and cholesterol synthesis decreases in hepatocytes. In familial hypercholesterolemia type II, LDL cannot be taken up into hepatocytes. Because HMG-CoA reductase is not properly inhibited, excessive cholesterol levels result. Triglyceride digestion in chylomicrons, the level of VLDL, the level of HDL, and conversion of VLDL to IDL are not affected in type II hypercholesterolemia.

17

10. A 25-year-old woman presents with a low red blood cell count, corneal opacities, and kidney insufficiency. She is diagnosed with LCAT deficiency. LCAT is involved in which of the following processes?
(A) Converting cholesterol to cholesterol esters
(B) The transfer of cholesterol esters from HDL to other lipoproteins
(C) Endocytosis of HDL particles into hepatocytes
(D) Hydrolysis of HDL
(E) Decreased uptake of cholesterol by hepatocytes

A. LCAT converts cholesterol to cholesterol esters, which accumulate in the core of HDL. This is an important part of reverse cholesterol transport. These cholesterol esters are transferred from HDL to VLDL and LDL (via the cholesterol ester transfer protein reaction),
which are then taken up by receptors in the liver. Therefore, LCAT is important for removing cholesterol from peripheral cells by inducing esterification of cholesterol, thus allowing eventual cholesterol uptake by the liver. LCAT is not involved in endocytosis of HDL into hepatocytes, in the transfer of cholesterol esters from HDL to other lipoproteins, or in hydrolysis of HDL.