ME04 - Cholesterol Synthesis, Transport and Export

Question 1

What are the Biologic Importance of Cholesterol?

Answer 1

Structural component of all cell membranes

Question 2

Cholesterol Synthesis and Transport

Answer 2

Liver (Biliary CHOL 2g/d)&raquo_space; Stomach (Dietary CHOL 0.4g/d)&raquo_space; Duodenum&raquo_space; Jejunum&raquo_space; Ileum (ABSORPTION 50%)&raquo_space; Colon (Fecal excretion 1.2 g/d)

Question 3

When CHOL is transported through a channel and pumped back out by a complex. Ezetimibe acts which part?

Answer 3

Ezetimibe acts on NPC1L3

Question 4

CHOLESTEROL STRUCTURE

Answer 4

Highly hydrophobic

Question 5

Steroids with 8 to 10 carbon atoms in the side chain at C17 and a hydroxyl group at C3

Answer 5

Sterols

Question 6

Major sterol in animal tissues

Answer 6

Cholesterol

Question 7

Cholesterol with a fatty acid attached at C3 and esterified

Answer 7

Cholesteryl Esters (CE) | Not normally found in membranes

Question 8

Why are Cholesteryl Esters esterified?

Answer 8

This makes the structure even more hydrophobic than free cholesterol

Question 9

Fate of Cholesteryl Esters

Answer 9

Must be transported in association with a protein (lipoprotein), or be solubilized by phospholipids and bile salts in bile

Question 10

SYNTHESIS OF CHOLESTEROL

Answer 10

Cholesterol is synthesized by virtually all tissues, but is largely contributed by the liver, intestine, adrenal cortex, and reproductive tissues

Question 11

8 Steps of Cholesterol Synthesis

Answer 11

1. Mevalonate/Mevalonic Acid (6C) is converted to Mevalonate 5 phosphate in 2 steps requiring ATP

Question 12

SYNTHESIS OF 3-HYDROXY-3- METHYGLUTARYL CoA (HMG CoA)

Answer 12

Similar to the pathway that produces ketone bodies

Question 13

Rate-limiting step in cholesterol synthesis

Answer 13

HMG-CoA&raquo_space; (HMG-CoA Reductase)&raquo_space; Mevalonate

Question 14

An intrinsic membrane protein of the ER with the catalytic domain projecting into the cytosol

Answer 14

HMG CoA reductase

Question 15

What inhibits in the rate-limiting step of Cholesterol Synthesis

Answer 15

This step is inhibited by statins (Simvastatin, Atorvasatin, etc.)

Question 16

What catalyzes many of the reactions involved in converting lanosterol to cholesterol and other steroids

Answer 16

cytochrome P450 enzyme superfamily

Question 17

An intermediate on the pathway for cholesterol synthesis,

Answer 17

Farnesyl pyrophosphate

Question 18

FARNESYL PYROPHOSPHATE/DIPHOSPHATE GIVES RISE TO:

Answer 18

DOLICHOL for the synthesis of N-glycosides

Question 19

What is the major control point in the REGULATION OF CHOLESTEROL SYNTHESIS

Answer 19

The reaction catalyzed by HMG CoA reductase, which is inhibited by mevalonate, cholesterol, and statin drugs

Question 20

What is only inhibited by dietary cholesterol

Answer 20

Hepatic synthesis

Question 21

What increases HMG CoA reductase activity?

Answer 21

Insulin or thyroid hormone

Question 22

What decreases HMG CoA reductase activity?

Answer 22

Glucagon or Glucocorticoids

Question 23

CELL CHOLESTEROL INCREASE IS DUE TO:

Answer 23

Uptake of cholesterol-containing lipoproteins by receptors

Question 24

CELL CHOLESTEROL DECREASE IS DUE TO:

Answer 24

Efflux of cholesterol from the cell membrane to HDL promoted by LCAT (lecithin:cholesterol acyltransferase). LCAT is also known as PCAT

Question 25

WHAT IS THE ROLE OF CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) IN PLASMA LIPID TRANSPORT

Answer 25

CETP facilitates the transfer of CE from HDL to VLDL, IDL, and LDL in exchange for TAG.

Question 26

What is VLDL and function of VLDL

Answer 26

VLDL is produced from the liver and is composed mostly of TAG

Question 27

What is LDL and function of LDL

Answer 27

LDL contains less TAG than VLDL

Question 28

The ring structure of cholesterol cannot be metabolized to carbon dioxide and water in humans. True or False?

Answer 28

True.

Question 29

How is the intact sterol nucleus eliminated?

Answer 29

The intact sterol nucleus is eliminated by conversion to bile acids and bile salts

Question 30

Predominant mechanisms for the excretion of excess cholesterol

Answer 30

Synthesis of bile acids

Question 31

The excretion of cholesterol in the form of bile acids is insufficient to compensate for an excess dietary intake of cholesterol. True or False?

Answer 31

True.

Question 32

Some of the cholesterol in the intestine is modified by bacteria before excretion. What do you call the primary compound made ?

Answer 32

Coprostanol

Question 33

Consists of a watery mixture of organic and inorganic compounds

Answer 33

Bile

Question 34

Quantitatively the most important organic components of bile

Answer 34

Lecithin and bile salts (conjugated bile acids)

Question 35

Fate of Bile

Answer 35

Can pass directly from the liver where it is synthesized to the duodenum through the common bile duct, or be stored in the gallbladder

Question 36

STRUCTURE OF BILE ACIDS

Answer 36

Contains 24 carbons with 2 or 3 hydroxyl groups and a side chain that terminates in a carboxyl group

Question 37

The rate limiting step in bile acid synthesis

Answer 37

The reaction catalyzed by the 7_-hydroxylase

Question 38

What is responsible for the down-regulation and up regulation of the limiting step?

Answer 38

Down-regulated by cholic acid

Question 39

SYNTHESIS OF BILE SALTS

Answer 39

Before the bile acids leave the liver, they are conjugated to a molecule of either glycine or taurine by an amide bond between the carboxyl group of the bile acid and the amino group of the added compound

Question 40

Where does Conjugation of bile salts takes place

Answer 40

Peroxisomes

Question 41

The ratio of glycine to taurine forms in the bile

Answer 41

3:01

Question 42

The salt forms of bile salts are fully ionized (negatively charged) at physiologic pH. True or False?

Answer 42

TRUE

Question 43

Rationale behind why bile salts are more effective solubilizers

Answer 43

Because of their enhanced amphipathic nature

Question 44

What is the ACTION OF INTESTINAL FLORA ON BILE SALTS

Answer 44

Bacteria in the intestine can remove glycine and taurine and regenerate bile acids

Question 45

What are the precursor or Deoxycholic Acid and Lithocholic Acid

Answer 45

DEOXYCHOLIC ACID FROM GLYCOCHOLIC ACID

Question 46

Fate of Bile Salts

Answer 46

Of the 15 to 30 grams of bile salts secreted from the liver, more than 95% are reabsorbed through the ileum, pass through the portal vein, and are reused

Question 47

What are Bile acid sequestrants and their function

Answer 47

Bile acid sequestrants like cholestyramine bind bile acids in the gut and prevent their reabsorption, promoting cholesterol excretion

Question 48

Due to the deposition of cholesterol and cholesteryl ester from the plasma lipoproteins to the artery walls

Answer 48

Atherosclerosis

Question 49

What protects a person from Atherosclerosis?

Answer 49

A high HDL and low LDL protects a person from this complication. This is one of the benefits provided by exercise

Question 50

What are the events leading to Atherosclerosis?

Answer 50

Endothelial Dysfunction >> Inflammation >> Oxidation >> Plaque instability and thrombus

Question 51

Event when an embolus blocks the coronary arteries

Answer 51

Myocardial Infarction

Question 52

Due to various defects in lipoprotein formation, transport, or destruction

Answer 52

DYSLIPOPROTEINEMIAS

Question 53

What are some of the diseases that exhibit abnormal lipoprotein patterns that resemble dyslipoproteinemias

Answer 53

Diabetes Mellitus, Hypothyroidism, Kidney disease, and atherosclerosis

Question 54

Occurs when more cholesterol enters the bile than can be solubilized by the bile salts and lecithin present

Answer 54

CHOLELITHIASIS (GALLSTONES)

Question 55

What is the treatment of choice for Cholelithiasis?

Answer 55

Surgery is the treatment of choice, but administration of chenodeoxycholic acid may help to supplement the bodys supply of bile acids